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Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada
Original Research
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GYNECOLOGY
Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada Gillian E. Hanley, PhD; Janice S. Kwon, MD; Sarah J. Finlayson, MD; David G. Huntsman, MD; Dianne Miller, MD; Jessica N McAlpine, MD
BACKGROUND: Recent evidence has suggested that the fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer. As a result, many Colleges of Obstetrics and Gynecology, including the American College of Obstetricians and Gynecology, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. OBJECTIVE: Previous research with the use of hospital data has indicated good perioperative safety of opportunistic salpingectomy, but no data on minor complications have been presented. Herein, we examine whether women who undergo opportunistic salpingectomy are at increased risk of minor complications after surgery. STUDY DESIGN: We identified all women in British Columbia who underwent opportunistic salpingectomy between 2008 and 2014 and examined all physician visits in the 2 weeks after discharge from the hospital. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We examined visits for surgical infection, surgical complication, orders for laboratory tests, and orders for imaging (x-ray, ultrasound scan, or computed tomography scan) and whether women who underwent opportunistic salpingectomy were more likely to fill a prescription for an antibiotic or analgesic in the 2 weeks after discharge from the hospital. We calculated adjusted odds ratios for these
O
varian cancer is a significant cause of cancer-related death, with approximately 25,000 new diagnoses and approximately 16,000 deaths from the disease annually in the United States and Canada combined. It is diagnosed commonly in advanced stages, when survival rates are low. This is partly a result of the lack of effective screening
Cite this article as: Hanley GE, Kwon JS, Finlayson SJ, et al. Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada. Am J Obstet Gynecol 2018;219:172.e1-8. 0002-9378/$36.00 ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.ajog.2018.05.019
outcomes, adjusting for other gynecologic conditions, surgical approach, and patient age. RESULTS: We included 49,275 women who had undergone a hysterectomy alone, a hysterectomy with opportunistic salpingectomy, a hysterectomy with bilateral salpingo-oophorectomy, a tubal ligation, or an opportunistic salpingectomy for sterilization. In women who had undergone opportunistic salpingectomy, there was no increased risk for physician visits for surgical infection, surgical complication, ordering a laboratory test, or ordering imaging in the 2 weeks after discharge. There was no increased risk of filling a prescription for an antibiotic. However, women who underwent opportunistic salpingectomy were at approximately 20% increased odds of filling a prescription for an analgesic in the 2 weeks after discharge from the hospital (adjusted odds ratio, 1.23; 95% confidence interval, 1.15e1.32 for hysterectomy with opportunistic salpingectomy; adjusted odds ratio, 1.21; 95% confidence interval, 1.14e1.29 for opportunistic salpingectomy for sterilization). CONCLUSION: We report no differences in minor complications between women who undergo opportunistic salpingectomy and women who undergo hysterectomy alone or tubal ligation, except for a slightly increased likelihood of filling a prescription for analgesic medication in the immediate 2 weeks after discharge. Key words: bilateral salpingectomy, hysterectomy, ovarian cancer
prevention, sterilization
methods, because no death benefit has been demonstrated even with strict adherence to screening protocols.1e5 In the last decade, we have improved our understanding of epithelial ovarian cancer dramatically; along with this recognition came a growing body of evidence that the most common and lethal form of ovarian cancer (high-grade serous cancer) often originates in the fallopian tube.6e9 As a possible ovarian cancer prevention strategy, recommendations were made to discuss the removal of the fallopian tubes with women who had completed childbearing and were undergoing common gynecologic surgeries. In September 2010 the Ovarian Cancer Research team recommended to
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all gynecologic surgeons in the province of British Columbia (BC) Canada that, when operating in women at general population risk for ovarian cancer, they should consider (1) performing bilateral salpingectomy at the time of hysterectomy (even when the ovaries are being preserved) and (2) performing bilateral salpingectomy in place of tubal ligation for permanent sterilization. These procedures have come to be referred to as opportunistic salpingectomy (OS). The Ovarian Cancer Research recommendations were followed by a similar recommendation from the Society of Gynecologic Oncology of Canada10 and later by the Society of Gynecologic Oncology.11 More recently the American College of Obstetricians and
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AJOG at a Glance Why was this study conducted? We conducted the study to examine whether opportunistic salpingectomy, the removal of fallopian tubes at the time of hysterectomy or in lieu of tubal ligation for the purpose of ovarian cancer prevention, is associated with a higher rate of minor complications after surgery than hysterectomy alone or tubal ligation. Key Findings There are no differences in rates of minor complications among women who undergo opportunistic salpingectomy. There is a slightly increased likelihood of filling a prescription analgesic in the 2 weeks after discharge from surgery that is completely absent by 1 month after surgery. What does this add to what is known? This study adds to the existing body of evidence that opportunistic salpingectomy is a safe alternative to hysterectomy alone or tubal ligation. Gynecologists and the Society of Obstetricians and Gynecologists of Canada have supported the recommendation.12,13 This is a strategy aimed solely at women of general population risk for ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy remains the recommended prevention strategy among women with BRCA1 or BRCA2 mutations. Previous research has indicated a significant increase in uptake of bilateral salpingectomy in the United States14e16 and Canada.17e19 Research that has been examining the safety of OS has all been reassuring but has focused on major events that occur within the surgical hospital stay.16,18 To ensure the safety of OS, minor complications that could affect the quality of life of women who undergo this procedure and have an important impact on the healthcare system should also be examined. Herein, we examine whether women who underwent OS are at increased risk for physician visits, infections, minor surgical complications, increased antibiotic use, and increased analgesic use in the 2 weeks after their surgery, compared with women who underwent hysterectomy alone or tubal ligation.
Methods We conducted a population-based retrospective cohort study of all women who underwent a relevant surgical procedure in the Canadian province of British Columbia (population, 4.6
million) between 2008 and 2014. With approval of all Data Stewards (BC Ministry of Health, PharmaNet, BC Cancer Agency, and BC Vital Statistics), we used Population Data BC to access the Discharge Abstract Database,20 which is a database that contains all hospital stays and day surgeries in the province. These data were linked with data for all physician visits,21 and the BC PharmaNet, which is a database that contains all prescription drugs dispensed in an outpatient setting.22 All inferences, opinions, and conclusions are those of the authors and do not reflect the opinions or policies of the Data Stewards. Ethics approval was obtained from the University of British Columbia Behavioural Research Ethics Board. We identified patients who underwent each of the relevant procedures using Canadian Classification of Health Intervention codes. Each procedure is coded separately, so a patient who undergoes a hysterectomy with a bilateral salpingectomy has a code for each procedure. These codes also indicate the surgical approach for each surgery (ie, open, laparoscopic, or vaginal). We excluded patients who were <15 years old or who had a diagnosis of gynecologic cancer. We grouped the data according to the procedures and stratified them into 5 groups: (1) women who had undergone a hysterectomy with no concomitant oophorectomy or salpingectomy (referred to as hysterectomy alone); (2) women who underwent a hysterectomy
Original Research
and a bilateral salpingectomy (hysterectomy with OS); (3) women who underwent a hysterectomy with a bilateral salpingo-oophorectomy (BSO; hysterectomy with BSO); (4) women who underwent a tubal ligation; and (5) women who had a bilateral salpingectomy alone with a diagnosis code that indicated that the procedure was for sterilization (International Classification of Diseases, Tenth Revision [ICD-10]CM Z.30.2). We did not include women who underwent hysteroscopic tubal occlusion. We used diagnostic codes in the hospital stay to examine other gynecologic conditions that were present in the woman (some of which were likely indications for the surgery) that included endometriosis (ICD-10 CA N80.X), leiomyoma (ICD-10 CA D25.X), benign ovarian or uterine neoplasm (ICD-10 CA D26.X, D27.X, D28.7), abnormal bleeding (ICD-10 CA N92.X, N93.X), pelvic organ prolapse (ICD-10 CA N81.X), pelvic inflammatory disease (ICD-10 CA N73.X, N74.X), and hydrosalpinx (ICD-10 CA N70.X). We defined minor complications as any complication that would result in a visit to the physician’s office but would not have been present during the initial hospital stay and would likely not result in a readmission to the hospital. To this end, we included physician visits in the 2 weeks after discharge from the hospital for the relevant surgery that were for surgical infection or surgical complication, that resulted in a laboratory test ordered, or that resulted in an order for imaging (X-ray, ultrasound scan, or computed tomography scan). We also included a count of the number of physician visits in the 2 weeks after discharge because women who experienced more complications or adverse effects might see their physician more frequently. We then examined whether women who underwent OS were more likely to fill a prescription for an antibiotic or a prescription-strength analgesic (excluding analgesics that are available over the counter [eg, acetaminophen, ibuprofen, naproxen]) in the 2 weeks after discharge from the hospital for their surgery (identified
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using Anatomical Therapeutic Classification Codes; J01 for antibiotics and N02A and N02B for analgesics). We examined differences between minor complication rates between women who underwent OS or hysterectomy with BSO and women who underwent the comparator surgery (hysterectomy alone is the comparator for all hysterectomies, and tubal ligation is the comparator for OS for sterilization) using chi-squared tests for categoric variables and independent sample t tests for continuous variables. We ran logistic regression, controlling for patient age at surgery, other gynecologic conditions (listed earlier), surgical approach, and cesarean section among women who underwent tubal sterilization (because a live birth was common in the same hospital stay as tubal sterilization).
Results There were 51,352 women who had undergone a hysterectomy alone, a hysterectomy with OS, a hysterectomy with BSO, a tubal ligation, or an OS for sterilization between 2008 and 2014 in British Columbia, Canada. We eliminated women who were 15 years of old at the time of surgery (number omitted because of small cell size) or women who were coded as having a gynecologic cancer (n¼2079); therefore, our final cohort included 49,275 women. In this study population, 8231 women underwent hysterectomy alone; 8508 women underwent hysterectomy with OS; 7273 women underwent hysterectomy with BSO; 19,424 women underwent tubal ligation, and 5839 women underwent OS for sterilization. Table 1 shows the characteristics of women who underwent each of these procedures in our cohort. Because the recommendations for OS were published in September 2010, the mean year of surgery is significantly later among women who underwent OS. Women who underwent hysterectomy with OS were significantly more likely to experience comorbid gynecologic conditions compared with women who underwent hysterectomy alone, except that they were significantly less likely to have a prolapse (9.2% vs 18.8%; P<.001).
Women who underwent hysterectomy with BSO had even higher rates of the comorbid gynecologic conditions, with the exception of prolapse and abnormal bleeding that were slightly less common in this group. There were no differences in income quintiles or the delivery of a baby in the same hospital stay; women who underwent hysterectomy with BSO were significantly older at surgery (46.8 vs 43.1; P<.001). Women who underwent OS for sterilization were slightly older (36.4 vs 35.3 years; P<.001), were less likely to have delivered a baby in the same hospital stay (36.2% vs 42.1%; P<.001), and were of higher income (P<.001) than women who underwent tubal ligation. They were more likely to have endometriosis (4.2% vs 2.3%; P<.001), a benign uterine or ovarian neoplasm (1.8% vs 0.6%; P<.001), abnormal bleeding (10.2% vs 6.7%; P<.001), and pelvic inflammatory disease (3.0% vs 1.8%; P<.001). There were no differences in rates of uterine leiomyoma and prolapse, and the women were less likely to have hydrosalpinx (0.5% vs 0.9%; P¼.004). The laparoscopic approach (41.5% vs 8.1; P<.001) and abdominal approach (44.7% vs 41.1%; P<.001) was more common in women who underwent hysterectomy with OS than in women who underwent hysterectomy alone; the vaginal approach was significantly less common in women who underwent hysterectomy with OS (17.9% vs 50.3%; P<.001). The abdominal approach was less common in women who underwent OS for sterilization (38.8% vs 43.5%; P<.001), and the laparoscopic approach (62.9% vs 56.0%; P<.001) and the vaginal approach (14.5% vs 10.9%; P<.001) were more common than in women who underwent tubal ligation. With respect to crude rates of minor complications, Table 2 shows that there was no difference between the women who underwent hysterectomy with OS or hysterectomy with BSO compared with women who underwent hysterectomy alone in terms of visits to physicians regarding a surgical infection or surgical complication in the 2 weeks after discharge from the hospital and any laboratory tests that were ordered in the
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ajog.org 2 weeks after discharge from the hospital for the hysterectomy. There were also slightly more women in the hysterectomy with OS group who had imaging ordered in the 2 weeks after hysterectomy (7.7% in women with OS vs 6.9% in women with hysterectomy alone; P¼.038). There were significantly fewer women who filled a prescription for an antibiotic in the hysterectomy with OS group (16.0% vs 17.9%; P¼.001). There were significantly more women filling a prescription for an analgesic in the 2 weeks after surgery among those who underwent hysterectomy with OS (60.0% vs 53.7%; P<.001) and those who underwent hysterectomy with BSO (55.9% vs 53.7%; P¼.006) compared with those who underwent hysterectomy alone. The only significant difference between women who underwent OS for sterilization and women who underwent tubal ligation was a higher rate of filling a prescription for an analgesic among women with OS (43.2% vs 37.6%; P<.001). Table 3 shows adjusted odds ratios for all minor complications that were adjusted for patient age, other gynecologic conditions, and surgical approach. Across both OS groups, there was no difference between women who underwent OS and women who underwent the control surgery (hysterectomy alone and tubal ligation, respectively) in visits to physicians regarding a surgical infection or surgical complication, any laboratory tests or imaging that was ordered, or antibiotic prescriptions that were filled. The only significant difference was in the likelihood of filling a prescription for an analgesic. The adjusted odds ratios (aOR) for women who underwent hysterectomy with OS and OS for sterilization were 1.23 (95% confidence interval [CI], 1.15e1.32) and 1.21 (95% CI, 1.14e1.29), respectively. There were no significant differences in any outcomes that were measured between women who underwent hysterectomy with BSO and women who underwent hysterectomy alone. To better understand the differences in rates of filling a prescription analgesic, we conducted further analyses (Table 4). We report that significantly more women in the OS groups were using a
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TABLE 1
Characteristics of women according to their surgery type
Variable
Hysterectomy alone (n¼8231)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Year of surgery, mean (SD)
2009.8 (1.8)
Age at time of surgery, mean years (SD) Delivered a baby in the same hospital stay, n (%)
P valuea
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
P valuea
2012.1 (1.6)
<.001
2010.9 (2.0)
<.001
2010.3 (1.9)
43.1 (6.7)
43.4 (6.2)
.006
46.8 (6.7)
<.001
69 (0.8)
17 (0.2)
16 (0.2)
<.001
1
1476 (18.1)
1585 (18.9)
2
1659 (20.4)
3
1743 (21.4)
4 5
Opportunistic salpingectomy for sterilization (n¼5839)
P value
2012.6 (1.2)
<.001
35.3 (5.7)
36.4 (5.6)
<.001
8167 (42.1)
2114 (36.2)
<.001
1337 (18.6)
4374 (22.9)
1257 (21.8)
1676 (20.0)
1517 (21.2)
4470 (23.4)
1230 (21.3)
1770 (21.1)
1502 (20.9)
3990 (20.9)
1216 (21.1)
1759 (21.6)
1819 (21.7)
1443 (20.1)
3527 (18.4)
1176 (20.4)
1501 (18.4)
1553 (18.5)
.768
1373 (19.1)
.132
2772 (14.5)
894 (15.5)
<.001
Endometriosis
1461 (17.8)
1802 (21.2)
<.001
2262 (31.1)
<.001
444 (2.3)
249 (4.2)
<.001
Uterine leiomyoma
3075 (37.4)
3849 (45.2)
<.001
3349 (46.1)
<.001
163 (0.8)
59 (1.0)
.219
Benign uterine or ovarian neoplasm
87 (1.1)
158 (1.9)
<.001
797 (11.0)
<.001
123 (0.6)
105 (1.8)
<.001
<.001
Tubal ligation (n¼19,424)
Income quintile, n (%)
Comorbid gynecologic conditions, n (%)
786 (9.2)
<.001
425 (5.8)
<.001
120 (0.6)
34 (0.6)
4680 (56.9)
5121 (60.2)
<.001
2580 (35.5)
<.001
1309 (6.7)
593 (10.2)
<.001
Pelvic inflammatory disease
223 (2.7)
287 (3.4)
.012
652 (9.0)
<.001
343 (1.8)
174 (3.0)
<.001
30 (0.4)
133 (1.6)
<.001
262 (3.6)
<.001
175 (0.9)
30 (0.5)
.004
3385 (41.1)
3801 (44.7)
<.001
4906 (67.5)
<.001
8440 (43.5)
2263 (38.8)
<.001
667 (8.1)
3533 (41.5)
<.001
2023 (27.8)
<.001
10886 (56.0)
3670 (62.9)
<.001
4139 (50.3)
1521 (17.9)
<.001
639 (8.8)
<.001
2124 (10.9)
844 (14.5)
<.001
Hydrosalpinx
.760
Surgical approach, n (%) Abdominal/open Laparoscopic Vaginal a
Comparisons use hysterectomy alone as the reference group. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
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1544 (18.8)
Abnormal bleeding
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Prolapse
.086 564 (9.7) 2027 (10.4) Comparisons use hysterectomy alone as the reference group. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
1477 (17.9) Antibiotics
1360 (18.7) .001 1364 (16.0)
.225
7294 (37.6) .006 4066 (55.9) <.001 5106 (60.0) 4419 (53.7) Prescription analgesic medication
Potentially relevant prescription drug use within 2 weeks of leaving the hospital after surgery, n (%)
565 (6.9) Imaging ordered, n (%)
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a
<.001 2524 (43.2)
.567 345 (5.9) 1109 (5.7) 479 (6.6) .038 655 (7.7)
.409
.331 765 (13.1) 2641 (13.6) 1344 (16.3) Laboratory test ordered, n (%)
1259 (17.3) .211 1329 (15.6)
.103
.289 292 (5.0) 1040 (5.4) 276 (3.4) Visit for surgical complication, n (%)
225 (3.1) .822 280 (3.3)
.362
.547 196 (3.4) 684 (3.5) 186 (2.3)
130 (1.8) .279 214 (2.5)
.038
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Visit for surgical infection, n (%)
.076 2.31.9 2.21.9 <.001 Physician visits in two weeks after surgery, mean (SD)
1.72.1
1.72.0
.101
1.82.1
P valuea P valuea Variable
Hysterectomy alone (n¼8231)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Rates of perioperative and postoperative complications by surgery type
TABLE 2
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
P value
Original Research
prescription analgesic before their surgery (5.7% vs 4.8% in the hysterectomy group and 2.5% vs 2.0% in the sterilization groups). The same is true with respect to women who underwent hysterectomy with BSO (6.9% vs 4.8%). However, even after removing women who used analgesics before surgery, women who underwent hysterectomy with OS and OS for sterilization were significantly more likely to fill a prescription for an analgesic in the 2 weeks after discharge than women who underwent a control surgery (aOR, 1.24 [95% CI, 1.15e1.33] for hysterectomy with OS and 1.21 [95% CI, 1.14e1.29 for OS for sterilization). The differences between groups had disappeared at 1 month after discharge, where aORs were 0.99 (95% CI, 0.84e1.16) and 1.03 (95% CI, 0.82e1.30). Finally, we analyzed according to the 3 types of analgesics that were responsible for 95.1% of filled prescriptions in our study population. Women in the OS groups and those who underwent hysterectomy with BSO were significantly less likely to fill a prescription for acetaminophen-codeine combinations (69% of prescriptions filled in our study population) than women in the control groups, but they were significantly more likely to fill prescriptions for hydromorphone (7% of prescriptions filled in our study population) or tramadol combinations (19% of prescriptions filled in our study population; Table 4).
Comment Our results suggest that women who underwent hysterectomy with OS, hysterectomy with BSO, and OS for sterilization were largely at statistically similar risk for the minor complications that we examined. They had similar numbers of physician visits in 2 weeks after discharge from the hospital, and they were no more likely to visit a physician for a surgical infection or complication. They were no more likely to have a laboratory test or imaging ordered, and they were no more likely to fill a prescription for an antibiotic. These findings are consistent with research from British Columbia, Canada, and from the United States that reported that overall hospital
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TABLE 3
Adjusted odds ratios of complications by surgery type Adjusted odds ratio (95% confidence interval)a
Variable
Hysterectomy alone (n¼8231; reference)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273; reference)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
Visit for surgical infection
1.00
1.14 (0.91e1.42)
0.82 (0.62e1.09)
1.00
0.96 (0.82e1.14)
Visit for surgical complication
1.00
0.93 (0.77e1.12)
0.84 (0.67e1.04)
1.00
0.96 (0.84e1.10)
Laboratory test ordered
1.00
0.94 (0.86e1.04)
1.09 (0.98e1.21)
1.00
0.95 (0.87e1.04)
X-ray performed
1.00
1.03 (0.91e1.18)
0.99 (0.84e1.15)
1.00
1.04 (0.92e1.18)
Prescription analgesic use
1.00
1.23 (1.15e1.32)
1.03 (0.95e1.10)
1.00
1.21 (1.14e1.29)
Antibiotic use
1.00
0.92 (0.84e1.01)
1.16 (1.04e1.28)
1.00
0.94 (0.85e1.04)
a
Adjusted for patient age, associated gynecologic conditions, and surgical approach. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
readmission rates, blood transfusions, postoperative complication, and hospital length of stay were not different between women who underwent hysterectomy with OS and hysterectomy alone.16,18 There was, however, a statistically significant difference in the likelihood of filling a prescription analgesic in the 2 weeks after discharge. Women who underwent OS were significantly more likely to fill a prescription for a tramadol combination analgesic and for hydromorphone (although rates of hydromorphone were low across all groups). This result could be explained several ways. First, there may be a systematic difference between patients who undergo OS and those who undergo control procedures that predispose them to use more prescription analgesia. Table 1 suggests slightly higher rates of several comorbid gynecologic conditions that include endometriosis, benign neoplasms, abnormal bleeding, pelvic inflammatory disease, and hydrosalpinx (although rates of many of these conditions are very low across all groups). Given that rates of most of these conditions were highest among women who underwent hysterectomy with BSO and that women who underwent hysterectomy with BSO were not at increased risk of filling a prescription analgesic in the 2 weeks after discharge, this seems unlikely to be the explanation. Second, OS may be more painful than the control
surgeries to which we were comparing (hysterectomy alone and tubal ligation). Although we cannot rule out this possibility, it seems unlikely that it would be more painful than hysterectomy with BSO. Hysterectomy with OS is performed in a similar manner to hysterectomy with BSO, without additional incisions or operative time. Third, our results partly may reflect the changing nature of analgesic use in Canada (and beyond). Given that the mean year at surgery was approximately 2.5 years later in the OS group and that women were more likely to have been using prescription analgesics before their surgery, we may be reflecting larger trends in analgesic use in our data. However, this does not explain our findings because the significantly increased use of prescription analgesics remains in the OS groups, even after removing data for women who used these medicines before surgery; the increased rate of filling these medicines among women who underwent OS completely disappears by 1 month after discharge, which indicates that any difference is short-lived, and the difference likely reflects the filling of short prescriptions to be used in case of need. Future research will require patientreported outcome measures to better understand whether OS is more painful than hysterectomy alone or tubal ligation. Fourth, there could have been
differences in physician practice, such that those who offered hysterectomy with OS may have been more likely to prescribe postoperative prescription analgesia compared with those who offered hysterectomy alone. We were not able to examine provider-specific factors in this analysis. Alternatively, prescription practices may have been different across geographic areas, with higher rates of prescription analgesics offered by physicians in urban or academic centers with higher uptake of hysterectomy with OS compared with rural areas. Future research should examine whether increased prescription analgesia use in the 2 weeks after discharge is clinically meaningful to patients because the use of OS is increasing worldwide. This is likely because 5-year survival rates for ovarian cancer remain <50% and have not substantially changed in the last 2 decades.23e25 Although no benefit of OS has yet been demonstrated in our population (we require several more years of follow-up evaluation to demonstrate decreased rates of ovarian cancer among those who have undergone OS in BC), there are encouraging data that suggest that salpingectomy is an effective ovarian cancer prevention strategy. A recent metaanalysis revealed a significant decrease in the risk of OC occurrence in patients who underwent
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2.87 (2.58e3.19) 1.00b Adjusted for patient age, indication for surgery, and surgical approach; b Reference. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
1.00b
1.82 (1.64e2.02)
1.34 (1.18e1.52) a
Tramadol combinations, n (%)
Adjusted odds ratio (95% confidence interval)
Adjusted odds ratio (95% confidence interval)a
2.47 (2.05e2.98)
696 (11.9) 862 (4.44)
1.00 1.27 (1.07e1.52)
941 (13.0) 1489 (17.5)
1.69 (1.45e1.97) 1.00
779 (9.5)
199 (3.4) 284 (1.5) 425 (5.8) 635 (7.5)
b b
328 (3.98)
a
Hydromorphone, n (%)
Adjusted odds ratio (95% confidence interval)
Acetaminophen/codeine combinations, n (%)
Type of analgesic medication
a
1.00
1605 (27.5)
0.79 (0.73e0.84) 0.89 (0.83e0.95)
0.87 (0.81e0.85)
1.00
b
6058 (31.2) 2611 (35.9) 2959 (34.8) 3124 (38.0)
b
0.99 (0.84e1.16) 1.00
Adjusted odds ratio (95% confidence interval)
143 (2.5)
1.03 (0.82e1.30) 1.08 (0.89e1.30)
1.00
b
446 (2.3) 520 (7.2) 550 (6.5) 514 (6.2)
b a
Prescription analgesic use 1 month after surgery, n(%)
1.21 (1.14e1.29) 1.00b 1.02 (0.94e1.11) 1.24 (1.15e1.33) 1.00b Adjusted odds ratio (95% confidence interval)a
2442 (42.9) 7077 (37.2) 3768 (55.6) 4794 (59.8) 4170 (53.2)
1.22 (1.00e1.48)
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Prescription analgesic use after surgery after removing those who used medications before surgery, n (%)
1.00b 1.36 (1.14e1.61) 1.24 (1.06e1.45)
148 (2.5) 391 (2.0) 500 (6.9) 488 (5.7) 394 (4.8)
1.00b (ref) Adjusted odds ratio (95% confidence interval)a
Variable
Prescription analgesic use before surgery, n (%)
Hysterectomy with opportunistic salpingectomy (n¼8508) Hysterectomy alone (n¼8231)
Additional analyses regarding prescription analgesic use after surgery
TABLE 4
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
Original Research
bilateral salpingectomy relative to control subjects (odds ratio, 0.51; 95% CI, 0.35e0.71).26 This metaanalysis included data from a small study from Rochester, NY,27 a Danish retrospective cohort study,28 and most recently a population-based retrospective Swedish study.29 We expect OS to be more protective than indicated by these retrospective studies in which bilateral salpingectomy was being performed for pathologic reasons. When undertaking OS, doctors are very careful to ensure complete removal of all fimbriae, because the purpose of the surgery is prophylaxis. Thus, we would not dissuade women and their physicians from undertaking OS based on this short-term increase in filling prescriptions for analgesics. Our study has a few limitations, which include those common to studies of administrative datasets. First, our data are retrospective (although they were prospectively collected), and there is a risk of imprecision, given the dependence on database accuracy and physician coding. However, these imprecisions are unlikely to be related to OS status and thus are unlikely to be a source of significant bias. Second, we are also limited by the nature of our prescription drug data. PharmaNet has data on all prescriptions that have been filled, but this does not necessarily translate into usage of these drugs. Patients may have obtained their drugs from the pharmacy to be on hand “just in case” but decided that they did not need them. Furthermore, PharmaNet is restricted to prescription medicines; because many analgesics are available over the counter, we were unable to examine all analgesic use. Although our examination of patient characteristics in Table 1 did not indicate significant differences in income among women who undergo OS compared with the comparator surgeries, there may be differences in education level that influenced our results. We were unable to control for education level because these data are not available at a population level. Although a large prospective study of the effectiveness of OS is needed
ajog.org urgently, historical effectiveness studies suggest that bilateral salpingectomy (even for pathologic indications that would themselves increase the risk of ovarian cancer) does significantly decrease the risk for ovarian cancer. We report no differences in minor complications between women who undergo OS and women who undergo hysterectomy alone or tubal ligation, except for a slightly increased risk of filling a prescription for analgesic in the first 2 weeks after discharge from surgery, which is no longer present at 1 month after discharge. This risk will likely be far outweighed by the potential long-term benefit because OS is being practiced increasingly as an ovarian cancer prevention strategy.30 n References 1. Rosenthal AN, Fraser L, Manchanda R, et al. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol 2013;31:49e57. 2. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011;305:2295e303. 3. Kobayashi H, Yamada Y, Sado T, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 2008;18:414e20. 4. Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10:327e40. 5. Menon U, Ryan A, Kalsi J, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol 2015;33:2062e71. 6. Gao FF, Bhargava R, Yang H, Li Z, Zhao C. Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin? Hum Pathol 2013;44:1534e43. 7. Kindelberger DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31:161e9.
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8. Karst AM, Levanon K, Drapkin R. Modeling high-grade serous ovarian carcinogenesis from the fallopian tube. Proc Natl Acad Sci U S A 2011;108:7547e52. 9. Singh N, Gilks CB, Wilkinson N, McCluggage WG. Assessment of a new system for primary site assignment in high-grade serous carcinoma of the fallopian tube, ovary, and peritoneum. Histopathology 2015;67: 331e7. 10. The Society of Gynecologic Oncology of Canada. GOC Statement regarding salpingectomy and ovarian cancer prevention. Available at: https://g-o-c.org/wp-content/uploads/2015/ 09/7GOCStmt_2011Sep_SalpOvCa_EN.pdf. Accessed July 9, 2018. 11. Society of Gynecologic Oncology. SGO Clinical Practice Statement: salpingectomy for ovarian cancer. Available at: https://www. sgo.org/clinical-practice/guidelines/sgo-clinicalpractice-statement-salpingectomy-for-ovariancancer-prevention/. Accessed July 9, 2018. 12. American College of Obstetricians and Gynecologists. Committee Opinion No. 620: salpingectomy for ovarian cancer prevention. Obstet Gynecol 2015;125:279e81. 13. Salvador S, Scott S, Fancis JA, Agrawal A, Giede C. No. 344eOpportunistic salpingectomy and other methods of risk reduction for ovarian/ fallopian tube/peritoneal cancer in the general population. J Obstet Gynaecol Can 2017;39: 480e93. 14. Hicks-Courant KD. Growth in salpingectomy rates in the United States since 2000. Am J Obstet Gynecol 2016;215:666e7. 15. Mikhail E, Salemi JL, Mogos MF, Hart S, Salihu HM, Imudia AN. National trends of adnexal surgeries at the time of hysterectomy for benign indication, United States, 19982011. Am J Obstet Gynecol 2015;213: 713.e1e13. 16. Hanley GE, McAlpine JN, Pearce CL, Miller D. The performance and safety of bilateral salpingectomy for ovarian cancer prevention in the United States. Am J Obstet Gynecol 2017;216:270.e1e9. 17. Hanley G, McAlpine J, Kwon J, Mitchell G. Opportunistic salpingectomy for ovarian cancer prevention. Gynaecol Oncol Res Pract 2015;2: 1e9. 18. McAlpine JN, Hanley GE, Woo MM, et al. Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention. Am J Obstet Gynecol 2014;210:471.e1e11. 19. Sandoval C, Fung-Kee-Fung M, Gilks B, Murphy KJ, Rahal R, Bryant H. Examining the use of salpingectomy with hysterectomy in Canada. Curr Oncol 2013;20:173e5. 20. Canadian Institute for Health Information (2015). Discharge Abstract Database (Hospital Separations). V2. Population Data BC. Data Extract. MOH (2015). 21. British Columbia Ministry of Health (2015). Medical Services Plan (MSP) Payment Information File.V2. Population Data BC. Data extract.
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MOH. 2015. Available at: www.population.bc. ca/data. Accessed June 8, 2018. 22. BC Ministry of Health (2015). PharmaNet. V2. BC Ministry of Health. Data Extract. Data stewardship committee (2015). Available at: www.popdata.bc.ca/data. Accessed June 8, 2018. 23. Lim AWW, Mesher D, Gentry-Maharaj A, et al. Time to diagnosis of type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records. BJOG 2016;123: 1012e20. 24. Surveillance Epidemiology and End Results Program. Ovary Cancer Survival Statistics. Available at: https://seer.cancer.gov/statfacts/ html/ovary.html. Accessed June 8, 2018. 25. Tone AA, Salvador S, Finlayson SJ, et al. The role of the fallopian tube in ovarian cancer. Clin Adv Hematol Oncol 2012;10:296e306. 26. Yoon SH, Kim SN, Shim SH, Kang SB, Lee SJ. Bilateral salpingectomy can reduce the risk of ovarian cancer in the general population: a meta-analysis. Eur J Cancer 2016;55:38e46. 27. Lessard-Anderson CR, Handlogten KS, Molitor RJ, et al. Effect of tubal sterilization technique on risk of serous epithelial ovarian and primary peritoneal carcinoma. Gynecol Oncol 2014;135:423e7. 28. 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: 86e94. 29. Falconer H, Yin L, Gronberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 2015;107. 30. Kwon JS, McAlpine JN, Hanley GE, et al. Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy. Obstet Gynecol 2015;152:338e45.
Author and article information From the Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology (all authors), and the Department of Pathology & Laboratory Medicine (Dr Huntsman), University of British Columbia, Vancouver BC, Canada. Received April 5, 2018; revised May 17, 2018; accepted May 22, 2018. Supported by the Canadian Cancer Society Research Institute and the Canadian Institutes for Health Research and by donor funds from the Vancouver General Hospital and University of British Columbia Hospital Foundation. G.E.H. is supported by the Canadian Cancer Society Research Institute Capacity Development Award in Cancer Prevention and a CIHR New Investigator Award. The funding sources played no role in study design, collection of data, interpretation of data, writing of the report, or decision to submit the article for publication. The authors report no conflict of interest. Corresponding author: Gillian E. Hanley, PhD. Gillian. [email protected]
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Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada Gillian E. Hanley, PhD; Janice S. Kwon, MD; Sarah J. Finlayson, MD; David G. Huntsman, MD; Dianne Miller, MD; Jessica N McAlpine, MD
BACKGROUND: Recent evidence has suggested that the fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer. As a result, many Colleges of Obstetrics and Gynecology, including the American College of Obstetricians and Gynecology, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. OBJECTIVE: Previous research with the use of hospital data has indicated good perioperative safety of opportunistic salpingectomy, but no data on minor complications have been presented. Herein, we examine whether women who undergo opportunistic salpingectomy are at increased risk of minor complications after surgery. STUDY DESIGN: We identified all women in British Columbia who underwent opportunistic salpingectomy between 2008 and 2014 and examined all physician visits in the 2 weeks after discharge from the hospital. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We examined visits for surgical infection, surgical complication, orders for laboratory tests, and orders for imaging (x-ray, ultrasound scan, or computed tomography scan) and whether women who underwent opportunistic salpingectomy were more likely to fill a prescription for an antibiotic or analgesic in the 2 weeks after discharge from the hospital. We calculated adjusted odds ratios for these
O
varian cancer is a significant cause of cancer-related death, with approximately 25,000 new diagnoses and approximately 16,000 deaths from the disease annually in the United States and Canada combined. It is diagnosed commonly in advanced stages, when survival rates are low. This is partly a result of the lack of effective screening
Cite this article as: Hanley GE, Kwon JS, Finlayson SJ, et al. Extending the safety evidence for opportunistic salpingectomy in prevention of ovarian cancer: a cohort study from British Columbia, Canada. Am J Obstet Gynecol 2018;219:172.e1-8. 0002-9378/$36.00 ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.ajog.2018.05.019
outcomes, adjusting for other gynecologic conditions, surgical approach, and patient age. RESULTS: We included 49,275 women who had undergone a hysterectomy alone, a hysterectomy with opportunistic salpingectomy, a hysterectomy with bilateral salpingo-oophorectomy, a tubal ligation, or an opportunistic salpingectomy for sterilization. In women who had undergone opportunistic salpingectomy, there was no increased risk for physician visits for surgical infection, surgical complication, ordering a laboratory test, or ordering imaging in the 2 weeks after discharge. There was no increased risk of filling a prescription for an antibiotic. However, women who underwent opportunistic salpingectomy were at approximately 20% increased odds of filling a prescription for an analgesic in the 2 weeks after discharge from the hospital (adjusted odds ratio, 1.23; 95% confidence interval, 1.15e1.32 for hysterectomy with opportunistic salpingectomy; adjusted odds ratio, 1.21; 95% confidence interval, 1.14e1.29 for opportunistic salpingectomy for sterilization). CONCLUSION: We report no differences in minor complications between women who undergo opportunistic salpingectomy and women who undergo hysterectomy alone or tubal ligation, except for a slightly increased likelihood of filling a prescription for analgesic medication in the immediate 2 weeks after discharge. Key words: bilateral salpingectomy, hysterectomy, ovarian cancer
prevention, sterilization
methods, because no death benefit has been demonstrated even with strict adherence to screening protocols.1e5 In the last decade, we have improved our understanding of epithelial ovarian cancer dramatically; along with this recognition came a growing body of evidence that the most common and lethal form of ovarian cancer (high-grade serous cancer) often originates in the fallopian tube.6e9 As a possible ovarian cancer prevention strategy, recommendations were made to discuss the removal of the fallopian tubes with women who had completed childbearing and were undergoing common gynecologic surgeries. In September 2010 the Ovarian Cancer Research team recommended to
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all gynecologic surgeons in the province of British Columbia (BC) Canada that, when operating in women at general population risk for ovarian cancer, they should consider (1) performing bilateral salpingectomy at the time of hysterectomy (even when the ovaries are being preserved) and (2) performing bilateral salpingectomy in place of tubal ligation for permanent sterilization. These procedures have come to be referred to as opportunistic salpingectomy (OS). The Ovarian Cancer Research recommendations were followed by a similar recommendation from the Society of Gynecologic Oncology of Canada10 and later by the Society of Gynecologic Oncology.11 More recently the American College of Obstetricians and
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AJOG at a Glance Why was this study conducted? We conducted the study to examine whether opportunistic salpingectomy, the removal of fallopian tubes at the time of hysterectomy or in lieu of tubal ligation for the purpose of ovarian cancer prevention, is associated with a higher rate of minor complications after surgery than hysterectomy alone or tubal ligation. Key Findings There are no differences in rates of minor complications among women who undergo opportunistic salpingectomy. There is a slightly increased likelihood of filling a prescription analgesic in the 2 weeks after discharge from surgery that is completely absent by 1 month after surgery. What does this add to what is known? This study adds to the existing body of evidence that opportunistic salpingectomy is a safe alternative to hysterectomy alone or tubal ligation. Gynecologists and the Society of Obstetricians and Gynecologists of Canada have supported the recommendation.12,13 This is a strategy aimed solely at women of general population risk for ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy remains the recommended prevention strategy among women with BRCA1 or BRCA2 mutations. Previous research has indicated a significant increase in uptake of bilateral salpingectomy in the United States14e16 and Canada.17e19 Research that has been examining the safety of OS has all been reassuring but has focused on major events that occur within the surgical hospital stay.16,18 To ensure the safety of OS, minor complications that could affect the quality of life of women who undergo this procedure and have an important impact on the healthcare system should also be examined. Herein, we examine whether women who underwent OS are at increased risk for physician visits, infections, minor surgical complications, increased antibiotic use, and increased analgesic use in the 2 weeks after their surgery, compared with women who underwent hysterectomy alone or tubal ligation.
Methods We conducted a population-based retrospective cohort study of all women who underwent a relevant surgical procedure in the Canadian province of British Columbia (population, 4.6
million) between 2008 and 2014. With approval of all Data Stewards (BC Ministry of Health, PharmaNet, BC Cancer Agency, and BC Vital Statistics), we used Population Data BC to access the Discharge Abstract Database,20 which is a database that contains all hospital stays and day surgeries in the province. These data were linked with data for all physician visits,21 and the BC PharmaNet, which is a database that contains all prescription drugs dispensed in an outpatient setting.22 All inferences, opinions, and conclusions are those of the authors and do not reflect the opinions or policies of the Data Stewards. Ethics approval was obtained from the University of British Columbia Behavioural Research Ethics Board. We identified patients who underwent each of the relevant procedures using Canadian Classification of Health Intervention codes. Each procedure is coded separately, so a patient who undergoes a hysterectomy with a bilateral salpingectomy has a code for each procedure. These codes also indicate the surgical approach for each surgery (ie, open, laparoscopic, or vaginal). We excluded patients who were <15 years old or who had a diagnosis of gynecologic cancer. We grouped the data according to the procedures and stratified them into 5 groups: (1) women who had undergone a hysterectomy with no concomitant oophorectomy or salpingectomy (referred to as hysterectomy alone); (2) women who underwent a hysterectomy
Original Research
and a bilateral salpingectomy (hysterectomy with OS); (3) women who underwent a hysterectomy with a bilateral salpingo-oophorectomy (BSO; hysterectomy with BSO); (4) women who underwent a tubal ligation; and (5) women who had a bilateral salpingectomy alone with a diagnosis code that indicated that the procedure was for sterilization (International Classification of Diseases, Tenth Revision [ICD-10]CM Z.30.2). We did not include women who underwent hysteroscopic tubal occlusion. We used diagnostic codes in the hospital stay to examine other gynecologic conditions that were present in the woman (some of which were likely indications for the surgery) that included endometriosis (ICD-10 CA N80.X), leiomyoma (ICD-10 CA D25.X), benign ovarian or uterine neoplasm (ICD-10 CA D26.X, D27.X, D28.7), abnormal bleeding (ICD-10 CA N92.X, N93.X), pelvic organ prolapse (ICD-10 CA N81.X), pelvic inflammatory disease (ICD-10 CA N73.X, N74.X), and hydrosalpinx (ICD-10 CA N70.X). We defined minor complications as any complication that would result in a visit to the physician’s office but would not have been present during the initial hospital stay and would likely not result in a readmission to the hospital. To this end, we included physician visits in the 2 weeks after discharge from the hospital for the relevant surgery that were for surgical infection or surgical complication, that resulted in a laboratory test ordered, or that resulted in an order for imaging (X-ray, ultrasound scan, or computed tomography scan). We also included a count of the number of physician visits in the 2 weeks after discharge because women who experienced more complications or adverse effects might see their physician more frequently. We then examined whether women who underwent OS were more likely to fill a prescription for an antibiotic or a prescription-strength analgesic (excluding analgesics that are available over the counter [eg, acetaminophen, ibuprofen, naproxen]) in the 2 weeks after discharge from the hospital for their surgery (identified
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using Anatomical Therapeutic Classification Codes; J01 for antibiotics and N02A and N02B for analgesics). We examined differences between minor complication rates between women who underwent OS or hysterectomy with BSO and women who underwent the comparator surgery (hysterectomy alone is the comparator for all hysterectomies, and tubal ligation is the comparator for OS for sterilization) using chi-squared tests for categoric variables and independent sample t tests for continuous variables. We ran logistic regression, controlling for patient age at surgery, other gynecologic conditions (listed earlier), surgical approach, and cesarean section among women who underwent tubal sterilization (because a live birth was common in the same hospital stay as tubal sterilization).
Results There were 51,352 women who had undergone a hysterectomy alone, a hysterectomy with OS, a hysterectomy with BSO, a tubal ligation, or an OS for sterilization between 2008 and 2014 in British Columbia, Canada. We eliminated women who were 15 years of old at the time of surgery (number omitted because of small cell size) or women who were coded as having a gynecologic cancer (n¼2079); therefore, our final cohort included 49,275 women. In this study population, 8231 women underwent hysterectomy alone; 8508 women underwent hysterectomy with OS; 7273 women underwent hysterectomy with BSO; 19,424 women underwent tubal ligation, and 5839 women underwent OS for sterilization. Table 1 shows the characteristics of women who underwent each of these procedures in our cohort. Because the recommendations for OS were published in September 2010, the mean year of surgery is significantly later among women who underwent OS. Women who underwent hysterectomy with OS were significantly more likely to experience comorbid gynecologic conditions compared with women who underwent hysterectomy alone, except that they were significantly less likely to have a prolapse (9.2% vs 18.8%; P<.001).
Women who underwent hysterectomy with BSO had even higher rates of the comorbid gynecologic conditions, with the exception of prolapse and abnormal bleeding that were slightly less common in this group. There were no differences in income quintiles or the delivery of a baby in the same hospital stay; women who underwent hysterectomy with BSO were significantly older at surgery (46.8 vs 43.1; P<.001). Women who underwent OS for sterilization were slightly older (36.4 vs 35.3 years; P<.001), were less likely to have delivered a baby in the same hospital stay (36.2% vs 42.1%; P<.001), and were of higher income (P<.001) than women who underwent tubal ligation. They were more likely to have endometriosis (4.2% vs 2.3%; P<.001), a benign uterine or ovarian neoplasm (1.8% vs 0.6%; P<.001), abnormal bleeding (10.2% vs 6.7%; P<.001), and pelvic inflammatory disease (3.0% vs 1.8%; P<.001). There were no differences in rates of uterine leiomyoma and prolapse, and the women were less likely to have hydrosalpinx (0.5% vs 0.9%; P¼.004). The laparoscopic approach (41.5% vs 8.1; P<.001) and abdominal approach (44.7% vs 41.1%; P<.001) was more common in women who underwent hysterectomy with OS than in women who underwent hysterectomy alone; the vaginal approach was significantly less common in women who underwent hysterectomy with OS (17.9% vs 50.3%; P<.001). The abdominal approach was less common in women who underwent OS for sterilization (38.8% vs 43.5%; P<.001), and the laparoscopic approach (62.9% vs 56.0%; P<.001) and the vaginal approach (14.5% vs 10.9%; P<.001) were more common than in women who underwent tubal ligation. With respect to crude rates of minor complications, Table 2 shows that there was no difference between the women who underwent hysterectomy with OS or hysterectomy with BSO compared with women who underwent hysterectomy alone in terms of visits to physicians regarding a surgical infection or surgical complication in the 2 weeks after discharge from the hospital and any laboratory tests that were ordered in the
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ajog.org 2 weeks after discharge from the hospital for the hysterectomy. There were also slightly more women in the hysterectomy with OS group who had imaging ordered in the 2 weeks after hysterectomy (7.7% in women with OS vs 6.9% in women with hysterectomy alone; P¼.038). There were significantly fewer women who filled a prescription for an antibiotic in the hysterectomy with OS group (16.0% vs 17.9%; P¼.001). There were significantly more women filling a prescription for an analgesic in the 2 weeks after surgery among those who underwent hysterectomy with OS (60.0% vs 53.7%; P<.001) and those who underwent hysterectomy with BSO (55.9% vs 53.7%; P¼.006) compared with those who underwent hysterectomy alone. The only significant difference between women who underwent OS for sterilization and women who underwent tubal ligation was a higher rate of filling a prescription for an analgesic among women with OS (43.2% vs 37.6%; P<.001). Table 3 shows adjusted odds ratios for all minor complications that were adjusted for patient age, other gynecologic conditions, and surgical approach. Across both OS groups, there was no difference between women who underwent OS and women who underwent the control surgery (hysterectomy alone and tubal ligation, respectively) in visits to physicians regarding a surgical infection or surgical complication, any laboratory tests or imaging that was ordered, or antibiotic prescriptions that were filled. The only significant difference was in the likelihood of filling a prescription for an analgesic. The adjusted odds ratios (aOR) for women who underwent hysterectomy with OS and OS for sterilization were 1.23 (95% confidence interval [CI], 1.15e1.32) and 1.21 (95% CI, 1.14e1.29), respectively. There were no significant differences in any outcomes that were measured between women who underwent hysterectomy with BSO and women who underwent hysterectomy alone. To better understand the differences in rates of filling a prescription analgesic, we conducted further analyses (Table 4). We report that significantly more women in the OS groups were using a
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TABLE 1
Characteristics of women according to their surgery type
Variable
Hysterectomy alone (n¼8231)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Year of surgery, mean (SD)
2009.8 (1.8)
Age at time of surgery, mean years (SD) Delivered a baby in the same hospital stay, n (%)
P valuea
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
P valuea
2012.1 (1.6)
<.001
2010.9 (2.0)
<.001
2010.3 (1.9)
43.1 (6.7)
43.4 (6.2)
.006
46.8 (6.7)
<.001
69 (0.8)
17 (0.2)
16 (0.2)
<.001
1
1476 (18.1)
1585 (18.9)
2
1659 (20.4)
3
1743 (21.4)
4 5
Opportunistic salpingectomy for sterilization (n¼5839)
P value
2012.6 (1.2)
<.001
35.3 (5.7)
36.4 (5.6)
<.001
8167 (42.1)
2114 (36.2)
<.001
1337 (18.6)
4374 (22.9)
1257 (21.8)
1676 (20.0)
1517 (21.2)
4470 (23.4)
1230 (21.3)
1770 (21.1)
1502 (20.9)
3990 (20.9)
1216 (21.1)
1759 (21.6)
1819 (21.7)
1443 (20.1)
3527 (18.4)
1176 (20.4)
1501 (18.4)
1553 (18.5)
.768
1373 (19.1)
.132
2772 (14.5)
894 (15.5)
<.001
Endometriosis
1461 (17.8)
1802 (21.2)
<.001
2262 (31.1)
<.001
444 (2.3)
249 (4.2)
<.001
Uterine leiomyoma
3075 (37.4)
3849 (45.2)
<.001
3349 (46.1)
<.001
163 (0.8)
59 (1.0)
.219
Benign uterine or ovarian neoplasm
87 (1.1)
158 (1.9)
<.001
797 (11.0)
<.001
123 (0.6)
105 (1.8)
<.001
<.001
Tubal ligation (n¼19,424)
Income quintile, n (%)
Comorbid gynecologic conditions, n (%)
786 (9.2)
<.001
425 (5.8)
<.001
120 (0.6)
34 (0.6)
4680 (56.9)
5121 (60.2)
<.001
2580 (35.5)
<.001
1309 (6.7)
593 (10.2)
<.001
Pelvic inflammatory disease
223 (2.7)
287 (3.4)
.012
652 (9.0)
<.001
343 (1.8)
174 (3.0)
<.001
30 (0.4)
133 (1.6)
<.001
262 (3.6)
<.001
175 (0.9)
30 (0.5)
.004
3385 (41.1)
3801 (44.7)
<.001
4906 (67.5)
<.001
8440 (43.5)
2263 (38.8)
<.001
667 (8.1)
3533 (41.5)
<.001
2023 (27.8)
<.001
10886 (56.0)
3670 (62.9)
<.001
4139 (50.3)
1521 (17.9)
<.001
639 (8.8)
<.001
2124 (10.9)
844 (14.5)
<.001
Hydrosalpinx
.760
Surgical approach, n (%) Abdominal/open Laparoscopic Vaginal a
Comparisons use hysterectomy alone as the reference group. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
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1544 (18.8)
Abnormal bleeding
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Prolapse
.086 564 (9.7) 2027 (10.4) Comparisons use hysterectomy alone as the reference group. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
1477 (17.9) Antibiotics
1360 (18.7) .001 1364 (16.0)
.225
7294 (37.6) .006 4066 (55.9) <.001 5106 (60.0) 4419 (53.7) Prescription analgesic medication
Potentially relevant prescription drug use within 2 weeks of leaving the hospital after surgery, n (%)
565 (6.9) Imaging ordered, n (%)
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a
<.001 2524 (43.2)
.567 345 (5.9) 1109 (5.7) 479 (6.6) .038 655 (7.7)
.409
.331 765 (13.1) 2641 (13.6) 1344 (16.3) Laboratory test ordered, n (%)
1259 (17.3) .211 1329 (15.6)
.103
.289 292 (5.0) 1040 (5.4) 276 (3.4) Visit for surgical complication, n (%)
225 (3.1) .822 280 (3.3)
.362
.547 196 (3.4) 684 (3.5) 186 (2.3)
130 (1.8) .279 214 (2.5)
.038
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Visit for surgical infection, n (%)
.076 2.31.9 2.21.9 <.001 Physician visits in two weeks after surgery, mean (SD)
1.72.1
1.72.0
.101
1.82.1
P valuea P valuea Variable
Hysterectomy alone (n¼8231)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Rates of perioperative and postoperative complications by surgery type
TABLE 2
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
P value
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prescription analgesic before their surgery (5.7% vs 4.8% in the hysterectomy group and 2.5% vs 2.0% in the sterilization groups). The same is true with respect to women who underwent hysterectomy with BSO (6.9% vs 4.8%). However, even after removing women who used analgesics before surgery, women who underwent hysterectomy with OS and OS for sterilization were significantly more likely to fill a prescription for an analgesic in the 2 weeks after discharge than women who underwent a control surgery (aOR, 1.24 [95% CI, 1.15e1.33] for hysterectomy with OS and 1.21 [95% CI, 1.14e1.29 for OS for sterilization). The differences between groups had disappeared at 1 month after discharge, where aORs were 0.99 (95% CI, 0.84e1.16) and 1.03 (95% CI, 0.82e1.30). Finally, we analyzed according to the 3 types of analgesics that were responsible for 95.1% of filled prescriptions in our study population. Women in the OS groups and those who underwent hysterectomy with BSO were significantly less likely to fill a prescription for acetaminophen-codeine combinations (69% of prescriptions filled in our study population) than women in the control groups, but they were significantly more likely to fill prescriptions for hydromorphone (7% of prescriptions filled in our study population) or tramadol combinations (19% of prescriptions filled in our study population; Table 4).
Comment Our results suggest that women who underwent hysterectomy with OS, hysterectomy with BSO, and OS for sterilization were largely at statistically similar risk for the minor complications that we examined. They had similar numbers of physician visits in 2 weeks after discharge from the hospital, and they were no more likely to visit a physician for a surgical infection or complication. They were no more likely to have a laboratory test or imaging ordered, and they were no more likely to fill a prescription for an antibiotic. These findings are consistent with research from British Columbia, Canada, and from the United States that reported that overall hospital
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TABLE 3
Adjusted odds ratios of complications by surgery type Adjusted odds ratio (95% confidence interval)a
Variable
Hysterectomy alone (n¼8231; reference)
Hysterectomy with opportunistic salpingectomy (n¼8508)
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273; reference)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
Visit for surgical infection
1.00
1.14 (0.91e1.42)
0.82 (0.62e1.09)
1.00
0.96 (0.82e1.14)
Visit for surgical complication
1.00
0.93 (0.77e1.12)
0.84 (0.67e1.04)
1.00
0.96 (0.84e1.10)
Laboratory test ordered
1.00
0.94 (0.86e1.04)
1.09 (0.98e1.21)
1.00
0.95 (0.87e1.04)
X-ray performed
1.00
1.03 (0.91e1.18)
0.99 (0.84e1.15)
1.00
1.04 (0.92e1.18)
Prescription analgesic use
1.00
1.23 (1.15e1.32)
1.03 (0.95e1.10)
1.00
1.21 (1.14e1.29)
Antibiotic use
1.00
0.92 (0.84e1.01)
1.16 (1.04e1.28)
1.00
0.94 (0.85e1.04)
a
Adjusted for patient age, associated gynecologic conditions, and surgical approach. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
readmission rates, blood transfusions, postoperative complication, and hospital length of stay were not different between women who underwent hysterectomy with OS and hysterectomy alone.16,18 There was, however, a statistically significant difference in the likelihood of filling a prescription analgesic in the 2 weeks after discharge. Women who underwent OS were significantly more likely to fill a prescription for a tramadol combination analgesic and for hydromorphone (although rates of hydromorphone were low across all groups). This result could be explained several ways. First, there may be a systematic difference between patients who undergo OS and those who undergo control procedures that predispose them to use more prescription analgesia. Table 1 suggests slightly higher rates of several comorbid gynecologic conditions that include endometriosis, benign neoplasms, abnormal bleeding, pelvic inflammatory disease, and hydrosalpinx (although rates of many of these conditions are very low across all groups). Given that rates of most of these conditions were highest among women who underwent hysterectomy with BSO and that women who underwent hysterectomy with BSO were not at increased risk of filling a prescription analgesic in the 2 weeks after discharge, this seems unlikely to be the explanation. Second, OS may be more painful than the control
surgeries to which we were comparing (hysterectomy alone and tubal ligation). Although we cannot rule out this possibility, it seems unlikely that it would be more painful than hysterectomy with BSO. Hysterectomy with OS is performed in a similar manner to hysterectomy with BSO, without additional incisions or operative time. Third, our results partly may reflect the changing nature of analgesic use in Canada (and beyond). Given that the mean year at surgery was approximately 2.5 years later in the OS group and that women were more likely to have been using prescription analgesics before their surgery, we may be reflecting larger trends in analgesic use in our data. However, this does not explain our findings because the significantly increased use of prescription analgesics remains in the OS groups, even after removing data for women who used these medicines before surgery; the increased rate of filling these medicines among women who underwent OS completely disappears by 1 month after discharge, which indicates that any difference is short-lived, and the difference likely reflects the filling of short prescriptions to be used in case of need. Future research will require patientreported outcome measures to better understand whether OS is more painful than hysterectomy alone or tubal ligation. Fourth, there could have been
differences in physician practice, such that those who offered hysterectomy with OS may have been more likely to prescribe postoperative prescription analgesia compared with those who offered hysterectomy alone. We were not able to examine provider-specific factors in this analysis. Alternatively, prescription practices may have been different across geographic areas, with higher rates of prescription analgesics offered by physicians in urban or academic centers with higher uptake of hysterectomy with OS compared with rural areas. Future research should examine whether increased prescription analgesia use in the 2 weeks after discharge is clinically meaningful to patients because the use of OS is increasing worldwide. This is likely because 5-year survival rates for ovarian cancer remain <50% and have not substantially changed in the last 2 decades.23e25 Although no benefit of OS has yet been demonstrated in our population (we require several more years of follow-up evaluation to demonstrate decreased rates of ovarian cancer among those who have undergone OS in BC), there are encouraging data that suggest that salpingectomy is an effective ovarian cancer prevention strategy. A recent metaanalysis revealed a significant decrease in the risk of OC occurrence in patients who underwent
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2.87 (2.58e3.19) 1.00b Adjusted for patient age, indication for surgery, and surgical approach; b Reference. Hanley et al. Extended safety data demonstrates opportunistic salpingectomy is safe. Am J Obstet Gynecol 2018.
1.00b
1.82 (1.64e2.02)
1.34 (1.18e1.52) a
Tramadol combinations, n (%)
Adjusted odds ratio (95% confidence interval)
Adjusted odds ratio (95% confidence interval)a
2.47 (2.05e2.98)
696 (11.9) 862 (4.44)
1.00 1.27 (1.07e1.52)
941 (13.0) 1489 (17.5)
1.69 (1.45e1.97) 1.00
779 (9.5)
199 (3.4) 284 (1.5) 425 (5.8) 635 (7.5)
b b
328 (3.98)
a
Hydromorphone, n (%)
Adjusted odds ratio (95% confidence interval)
Acetaminophen/codeine combinations, n (%)
Type of analgesic medication
a
1.00
1605 (27.5)
0.79 (0.73e0.84) 0.89 (0.83e0.95)
0.87 (0.81e0.85)
1.00
b
6058 (31.2) 2611 (35.9) 2959 (34.8) 3124 (38.0)
b
0.99 (0.84e1.16) 1.00
Adjusted odds ratio (95% confidence interval)
143 (2.5)
1.03 (0.82e1.30) 1.08 (0.89e1.30)
1.00
b
446 (2.3) 520 (7.2) 550 (6.5) 514 (6.2)
b a
Prescription analgesic use 1 month after surgery, n(%)
1.21 (1.14e1.29) 1.00b 1.02 (0.94e1.11) 1.24 (1.15e1.33) 1.00b Adjusted odds ratio (95% confidence interval)a
2442 (42.9) 7077 (37.2) 3768 (55.6) 4794 (59.8) 4170 (53.2)
1.22 (1.00e1.48)
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Prescription analgesic use after surgery after removing those who used medications before surgery, n (%)
1.00b 1.36 (1.14e1.61) 1.24 (1.06e1.45)
148 (2.5) 391 (2.0) 500 (6.9) 488 (5.7) 394 (4.8)
1.00b (ref) Adjusted odds ratio (95% confidence interval)a
Variable
Prescription analgesic use before surgery, n (%)
Hysterectomy with opportunistic salpingectomy (n¼8508) Hysterectomy alone (n¼8231)
Additional analyses regarding prescription analgesic use after surgery
TABLE 4
Hysterectomy with bilateral salpingo-oophorectomy (n¼7273)
Tubal ligation (n¼19,424)
Opportunistic salpingectomy for sterilization (n¼5839)
Original Research
bilateral salpingectomy relative to control subjects (odds ratio, 0.51; 95% CI, 0.35e0.71).26 This metaanalysis included data from a small study from Rochester, NY,27 a Danish retrospective cohort study,28 and most recently a population-based retrospective Swedish study.29 We expect OS to be more protective than indicated by these retrospective studies in which bilateral salpingectomy was being performed for pathologic reasons. When undertaking OS, doctors are very careful to ensure complete removal of all fimbriae, because the purpose of the surgery is prophylaxis. Thus, we would not dissuade women and their physicians from undertaking OS based on this short-term increase in filling prescriptions for analgesics. Our study has a few limitations, which include those common to studies of administrative datasets. First, our data are retrospective (although they were prospectively collected), and there is a risk of imprecision, given the dependence on database accuracy and physician coding. However, these imprecisions are unlikely to be related to OS status and thus are unlikely to be a source of significant bias. Second, we are also limited by the nature of our prescription drug data. PharmaNet has data on all prescriptions that have been filled, but this does not necessarily translate into usage of these drugs. Patients may have obtained their drugs from the pharmacy to be on hand “just in case” but decided that they did not need them. Furthermore, PharmaNet is restricted to prescription medicines; because many analgesics are available over the counter, we were unable to examine all analgesic use. Although our examination of patient characteristics in Table 1 did not indicate significant differences in income among women who undergo OS compared with the comparator surgeries, there may be differences in education level that influenced our results. We were unable to control for education level because these data are not available at a population level. Although a large prospective study of the effectiveness of OS is needed
ajog.org urgently, historical effectiveness studies suggest that bilateral salpingectomy (even for pathologic indications that would themselves increase the risk of ovarian cancer) does significantly decrease the risk for ovarian cancer. We report no differences in minor complications between women who undergo OS and women who undergo hysterectomy alone or tubal ligation, except for a slightly increased risk of filling a prescription for analgesic in the first 2 weeks after discharge from surgery, which is no longer present at 1 month after discharge. This risk will likely be far outweighed by the potential long-term benefit because OS is being practiced increasingly as an ovarian cancer prevention strategy.30 n References 1. Rosenthal AN, Fraser L, Manchanda R, et al. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol 2013;31:49e57. 2. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011;305:2295e303. 3. Kobayashi H, Yamada Y, Sado T, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer 2008;18:414e20. 4. Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10:327e40. 5. Menon U, Ryan A, Kalsi J, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol 2015;33:2062e71. 6. Gao FF, Bhargava R, Yang H, Li Z, Zhao C. Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin? Hum Pathol 2013;44:1534e43. 7. Kindelberger DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am J Surg Pathol 2007;31:161e9.
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8. Karst AM, Levanon K, Drapkin R. Modeling high-grade serous ovarian carcinogenesis from the fallopian tube. Proc Natl Acad Sci U S A 2011;108:7547e52. 9. Singh N, Gilks CB, Wilkinson N, McCluggage WG. Assessment of a new system for primary site assignment in high-grade serous carcinoma of the fallopian tube, ovary, and peritoneum. Histopathology 2015;67: 331e7. 10. The Society of Gynecologic Oncology of Canada. GOC Statement regarding salpingectomy and ovarian cancer prevention. Available at: https://g-o-c.org/wp-content/uploads/2015/ 09/7GOCStmt_2011Sep_SalpOvCa_EN.pdf. Accessed July 9, 2018. 11. Society of Gynecologic Oncology. SGO Clinical Practice Statement: salpingectomy for ovarian cancer. Available at: https://www. sgo.org/clinical-practice/guidelines/sgo-clinicalpractice-statement-salpingectomy-for-ovariancancer-prevention/. Accessed July 9, 2018. 12. American College of Obstetricians and Gynecologists. Committee Opinion No. 620: salpingectomy for ovarian cancer prevention. Obstet Gynecol 2015;125:279e81. 13. Salvador S, Scott S, Fancis JA, Agrawal A, Giede C. No. 344eOpportunistic salpingectomy and other methods of risk reduction for ovarian/ fallopian tube/peritoneal cancer in the general population. J Obstet Gynaecol Can 2017;39: 480e93. 14. Hicks-Courant KD. Growth in salpingectomy rates in the United States since 2000. Am J Obstet Gynecol 2016;215:666e7. 15. Mikhail E, Salemi JL, Mogos MF, Hart S, Salihu HM, Imudia AN. National trends of adnexal surgeries at the time of hysterectomy for benign indication, United States, 19982011. Am J Obstet Gynecol 2015;213: 713.e1e13. 16. Hanley GE, McAlpine JN, Pearce CL, Miller D. The performance and safety of bilateral salpingectomy for ovarian cancer prevention in the United States. Am J Obstet Gynecol 2017;216:270.e1e9. 17. Hanley G, McAlpine J, Kwon J, Mitchell G. Opportunistic salpingectomy for ovarian cancer prevention. Gynaecol Oncol Res Pract 2015;2: 1e9. 18. McAlpine JN, Hanley GE, Woo MM, et al. Opportunistic salpingectomy: uptake, risks, and complications of a regional initiative for ovarian cancer prevention. Am J Obstet Gynecol 2014;210:471.e1e11. 19. Sandoval C, Fung-Kee-Fung M, Gilks B, Murphy KJ, Rahal R, Bryant H. Examining the use of salpingectomy with hysterectomy in Canada. Curr Oncol 2013;20:173e5. 20. Canadian Institute for Health Information (2015). Discharge Abstract Database (Hospital Separations). V2. Population Data BC. Data Extract. MOH (2015). 21. British Columbia Ministry of Health (2015). Medical Services Plan (MSP) Payment Information File.V2. Population Data BC. Data extract.
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MOH. 2015. Available at: www.population.bc. ca/data. Accessed June 8, 2018. 22. BC Ministry of Health (2015). PharmaNet. V2. BC Ministry of Health. Data Extract. Data stewardship committee (2015). Available at: www.popdata.bc.ca/data. Accessed June 8, 2018. 23. Lim AWW, Mesher D, Gentry-Maharaj A, et al. Time to diagnosis of type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records. BJOG 2016;123: 1012e20. 24. Surveillance Epidemiology and End Results Program. Ovary Cancer Survival Statistics. Available at: https://seer.cancer.gov/statfacts/ html/ovary.html. Accessed June 8, 2018. 25. Tone AA, Salvador S, Finlayson SJ, et al. The role of the fallopian tube in ovarian cancer. Clin Adv Hematol Oncol 2012;10:296e306. 26. Yoon SH, Kim SN, Shim SH, Kang SB, Lee SJ. Bilateral salpingectomy can reduce the risk of ovarian cancer in the general population: a meta-analysis. Eur J Cancer 2016;55:38e46. 27. Lessard-Anderson CR, Handlogten KS, Molitor RJ, et al. Effect of tubal sterilization technique on risk of serous epithelial ovarian and primary peritoneal carcinoma. Gynecol Oncol 2014;135:423e7. 28. 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: 86e94. 29. Falconer H, Yin L, Gronberg H, Altman D. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst 2015;107. 30. Kwon JS, McAlpine JN, Hanley GE, et al. Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention strategy. Obstet Gynecol 2015;152:338e45.
Author and article information From the Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology (all authors), and the Department of Pathology & Laboratory Medicine (Dr Huntsman), University of British Columbia, Vancouver BC, Canada. Received April 5, 2018; revised May 17, 2018; accepted May 22, 2018. Supported by the Canadian Cancer Society Research Institute and the Canadian Institutes for Health Research and by donor funds from the Vancouver General Hospital and University of British Columbia Hospital Foundation. G.E.H. is supported by the Canadian Cancer Society Research Institute Capacity Development Award in Cancer Prevention and a CIHR New Investigator Award. The funding sources played no role in study design, collection of data, interpretation of data, writing of the report, or decision to submit the article for publication. The authors report no conflict of interest. Corresponding author: Gillian E. Hanley, PhD. Gillian. [email protected]
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