Gynecologic Oncology Consult

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

Gynecological cancer in a woman of reproductive age is devastating news. Many women facing cancer treatment are interested in maintaining fertility. Fortunately, fertility-sparing treatment options are increasingly available and successful pregnancies have been reported.

These pregnancies present unique challenges to optimizing care of the mother and the fetus. In this article, we review the literature on pregnancies after successful treatment of ovarian, cervical, and endometrial cancer, and gestational trophoblastic disease.

Ovarian cancer

For young women diagnosed with ovarian cancer, the question of fertility preservation is often paramount. The American Society for Reproductive Medicine and the American Society of Clinical Oncology have published guidelines endorsing embryo and oocyte cryopreservation as viable strategies for maintaining fertility (J. Clin. Oncol. 2013;31:2500-10/ Fertil. Steril. 2013;100:1224-31).

Particularly with non–epithelial cell (germ cell) and borderline tumors, innovations in cryopreservation have become more widely available. Cryopreservation of immature oocytes in young girls is still considered investigational and should be undertaken as part of a research protocol. In a study of 62 women with epithelial ovarian cancer who underwent oocyte cryopreservation, there were 19 conceptions and 22 deliveries – all at term with no anomalies (Gynecol. Oncol. 2008;110:345-53).

However, pregnancies resulting from in vitro fertilization are at increased risk for anomalies and a targeted ultrasound and fetal echocardiogram are recommended.

Cervical cancer

In the United States, 43% of women diagnosed with cervical cancer are under age 45. For women with early-stage cancer with radiographically negative lymph nodes, tumors less than 2 cm, and no deep stromal invasion, fertility-sparing procedures include radical trachelectomy and simple vaginal trachelectomy.

Trachelectomy for appropriately selected patients is safe with recurrence rates of 2%-3% and death rates of 2%-5%. While experimental, for women with bulky disease (greater than 2 cm), neoadjuvant chemotherapy and subsequent trachelectomy has been reported (Gynecol. Oncol. 2014;135:213-6). While there is no consensus, most experts recommend 6 months to 1 year after surgery to attempt conception.

Conception rates after trachelectomy are promising with 60%-80% able to conceive. Approximately 10%-15% of these women will experience cervical stenosis, often attributed to the cerclage, resulting in menstrual or fertility issues (Gynecol. Oncol. 2005;99:S152-6/ Gyncol. Oncol. 2013;131:77-82). Placement of an intrauterine cannula (Smith sleeve) at the time of trachelectomy decreases the rate of stenosis (Gynecol. Oncol. 2012;124:276-80).

Pregnancy outcomes in several case series after trachelectomy have demonstrated a rate of first trimester loss of 13%-20%, second trimester loss of 5%-8%, and preterm delivery of 27%-51%, mostly secondary to preterm premature rupture of membranes (PPROM) and/or chorioamnionitis. Both preterm deliveries and midtrimester losses are thought to be secondary to cervical insufficiency, decreased cervical mucus, and ascending infection.

Women who have undergone fertility-sparing treatment for cervical cancer should be counseled about the challenges of pregnancy, including decreased fertility, risk of early and late miscarriage, and preterm delivery. Practitioners should consider cervical length surveillance, especially for those without a cerclage, and vaginal progesterone. The potential utility of preemptive antibiotics in this population is unclear, though early treatment of urinary or genital tract infections is prudent.

Endometrial cancer

As a consequence of the obesity epidemic, younger women are being diagnosed with endometrial hyperplasia and cancer. Approximately 25% of early stage endometrial cancers are diagnosed in premenopausal women, and 5% in women under age 40.

While hysterectomy is standard, fertility-sparing treatment with progestin for well-differentiated grade 1 stage 1A endometrial cancer has been successful and is not associated with any increase in disease progression and/or death (Obstet. Gynecol. 2013; 121:136-42).

Nearly two-thirds of the successfully treated women will require fertility medications and/or assisted reproductive technology (ART). Among those who conceive, 25% will miscarry. Following childbearing, definitive hysterectomy is recommended given the high recurrence rate (Gynecol. Oncol. 2014;133:229-33).

Gestational trophoblastic disease

Women with a history of complete and partial molar pregnancies and persistent gestational trophoblastic neoplasia (GTN) often pursue subsequent pregnancy. In a large cohort of more than 2,400 pregnancies after GTN, pregnancy outcomes were similar to those of the general population (J. Reprod. Med. 2014;59:188-94).

Among women with a history of a complete or partial mole, 1.7% had a subsequent pregnancy complicated by another molar pregnancy. Women who received chemotherapy for GTN may have a slightly higher risk of stillbirth (1.3%) and higher rates of anxiety in subsequent pregnancies (BJOG 2003;110:560-6).

Young women experiencing gynecologic malignancies are often concerned about the safety of pregnancy. In appropriately selected patients, fertility preservation is safe and pregnancy outcomes overall are favorable, although women should be counseled regarding reduced fertility, the need for ART, and the risks of prematurity and stillbirth.

Pregnant women with a history of cancer or gestational trophoblastic disease are also at high risk for depression and anxiety. Women with a personal history of gynecologic cancer or GTD should be followed by a multidisciplinary team that can address the obstetrical, oncological, and psychological aspects of pregnancy.

Dr. Smid is a second-year fellow in maternal-fetal medicine at the University of North Carolina at Chapel Hill. Dr. Ivester is an associate professor of maternal-fetal medicine and an associate professor of maternal child health at UNC-Chapel Hill. The authors reported having no financial disclosures.

Rudolph Virchow clearly demonstrated the association between malignancy and venous thromboembolic events. VTE – deep vein thrombosis and pulmonary embolism – affect between 15% and 38% of patients with gynecologic malignancies after surgery.

The rate of pulmonary embolism (PE) in this patient population can be as high as 6.8%, with the case fatality rate being 11%-12% (Obstet. Gynecol. 2012;119:155-67). Other factors associated with the development of VTE include prior VTE, older age, African American race, prolonged operative time, obesity, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of VTE in women undergoing gynecologic surgery is quadrupled in the presence of malignancy(Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE compared to matched controls (Gynecol. Oncol. 2007;106:439-45).

Additionally, cancer patients are typically older, have longer and more complex surgeries, and the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Although the treatment of VTE is fairly similar between patients with malignancy and those without cancer, treatment of a VTE in patients with cancer can be further complicated by higher VTE recurrence rates and increased risk of bleeding. Furthermore, issues related to the malignant disease process such as prognosis, presence and location of metastasis, and life expectancy should be taken into consideration when managing VTE in this patient population.

Generally, in the setting of an acute or recurrent VTE, initial therapy with a parenteral anticoagulant (heparin or low-molecular-weight heparins [LMWH]) should be immediately instituted in patients with a gynecologic malignancy, unless there is evidence of active bleeding or any other contraindication for the use of an anticoagulant.

Other factors associated with cancer such as immobilization, the presence of metastases, and impaired renal function with a creatinine clearance less than 30 mL/min, may increase the risk of bleeding complications but are not absolute contraindications to anticoagulation (Thromb. Haemost. 2008;100:435-9). The initial treatment phase, which last for 5-10 days, is then followed by a longer treatment phase lasting 3-6 months.

In the majority of cases, LMWH is the preferred agent for both the initial and prolonged treatment phase assuming adequate renal function. Based on evidence from a meta-analysis of 16 randomized controlled trials in cancer patients receiving initial anticoagulation for VTE, LMWH is associated with a 30% reduction in mortality without an increased risk of bleeding in comparison to unfractionated heparin (Cochrane Database. Syst. Rev. 2014;6:CD006649).

When compared with the vitamin K antagonist warfarin, LMWH appears to be associated with a significantly reduced rate of recurrent VTE (hazard ratio, 0.47; 95% confidence interval 0.32-0.71). However, this was not associated with a survival advantage (N. Engl. J. Med. 2003;349:146-53).

There are no trials comparing the different formulations of LMWH. In our practice, we routinely use the LMWH enoxaparin dosed at 1 mg/kg subcutaneously twice daily. Other well-studied LMWHs include dalteparin and tinzaparin.

LMWHs are primarily renally excreted, thus, in patients with compromised renal function, the biological half-life of the medication may be prolonged, leading to potential bleeding complications. The majority of LMWH trials excluded patients with creatinine clearance less than 30 mL/min, therefore, in patients with compromised renal function, one option would be to decrease the daily dose by as much as 50% and closely monitor antifactor XA levels. Alternatively, the use of unfractionated heparin in the acute setting followed by warfarin with close monitoring of the patient’s international normalized ratio could prove less cumbersome and ultimately safer for these patients. However, given the limitations of the currently available data we would not recommend the routine use of newer oral anticoagulation agents.

Patients with a malignancy are at increased risk for the development of a recurrent VTE even in the setting of anticoagulation. Some of the risks factors for this phenomenon include presence of central venous catheters, interruption of therapy for procedures, and immobilization. In cases of recurrent VTE, consideration should be given to extending the duration of treatment beyond the initial planned 3-6 months. Other patients that may benefit from extended therapy include those with continued immobility or active cancer burden.

LMWH is also the preferred agent for extended therapy based on very limited evidence from experimental studies suggesting that LMWH may have antineoplastic effects and thus a survival advantage. However, in the setting of a recurrent VTE, there is very limited data on which to base the choice of extended treatment. Options include switching the therapeutic agent, increasing the dose or frequency of administration, or placement of an inferior vena cava filter. Consultation with a hematologist may also be warranted in this and more complicated scenarios.

Ultimately, LMWH appears to be the best available therapy for patients with a gynecologic malignancy. However, the decision to anticoagulate should be carefully planned out, taking into consideration the individual patient’s disease burden and associated comorbidities in order to select the most appropriate treatment option.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant financial disclosures.

Rudolph Virchow clearly demonstrated the association between malignancy and venous thromboembolic events. VTE – deep vein thrombosis and pulmonary embolism – affect between 15% and 38% of patients with gynecologic malignancies after surgery.

The rate of pulmonary embolism (PE) in this patient population can be as high as 6.8%, with the case fatality rate being 11%-12% (Obstet. Gynecol. 2012;119:155-67). Other factors associated with the development of VTE include prior VTE, older age, African American race, prolonged operative time, obesity, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of VTE in women undergoing gynecologic surgery is quadrupled in the presence of malignancy(Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE compared to matched controls (Gynecol. Oncol. 2007;106:439-45).

Additionally, cancer patients are typically older, have longer and more complex surgeries, and the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Although the treatment of VTE is fairly similar between patients with malignancy and those without cancer, treatment of a VTE in patients with cancer can be further complicated by higher VTE recurrence rates and increased risk of bleeding. Furthermore, issues related to the malignant disease process such as prognosis, presence and location of metastasis, and life expectancy should be taken into consideration when managing VTE in this patient population.

Generally, in the setting of an acute or recurrent VTE, initial therapy with a parenteral anticoagulant (heparin or low-molecular-weight heparins [LMWH]) should be immediately instituted in patients with a gynecologic malignancy, unless there is evidence of active bleeding or any other contraindication for the use of an anticoagulant.

Other factors associated with cancer such as immobilization, the presence of metastases, and impaired renal function with a creatinine clearance less than 30 mL/min, may increase the risk of bleeding complications but are not absolute contraindications to anticoagulation (Thromb. Haemost. 2008;100:435-9). The initial treatment phase, which last for 5-10 days, is then followed by a longer treatment phase lasting 3-6 months.

In the majority of cases, LMWH is the preferred agent for both the initial and prolonged treatment phase assuming adequate renal function. Based on evidence from a meta-analysis of 16 randomized controlled trials in cancer patients receiving initial anticoagulation for VTE, LMWH is associated with a 30% reduction in mortality without an increased risk of bleeding in comparison to unfractionated heparin (Cochrane Database. Syst. Rev. 2014;6:CD006649).

When compared with the vitamin K antagonist warfarin, LMWH appears to be associated with a significantly reduced rate of recurrent VTE (hazard ratio, 0.47; 95% confidence interval 0.32-0.71). However, this was not associated with a survival advantage (N. Engl. J. Med. 2003;349:146-53).

There are no trials comparing the different formulations of LMWH. In our practice, we routinely use the LMWH enoxaparin dosed at 1 mg/kg subcutaneously twice daily. Other well-studied LMWHs include dalteparin and tinzaparin.

LMWHs are primarily renally excreted, thus, in patients with compromised renal function, the biological half-life of the medication may be prolonged, leading to potential bleeding complications. The majority of LMWH trials excluded patients with creatinine clearance less than 30 mL/min, therefore, in patients with compromised renal function, one option would be to decrease the daily dose by as much as 50% and closely monitor antifactor XA levels. Alternatively, the use of unfractionated heparin in the acute setting followed by warfarin with close monitoring of the patient’s international normalized ratio could prove less cumbersome and ultimately safer for these patients. However, given the limitations of the currently available data we would not recommend the routine use of newer oral anticoagulation agents.

Patients with a malignancy are at increased risk for the development of a recurrent VTE even in the setting of anticoagulation. Some of the risks factors for this phenomenon include presence of central venous catheters, interruption of therapy for procedures, and immobilization. In cases of recurrent VTE, consideration should be given to extending the duration of treatment beyond the initial planned 3-6 months. Other patients that may benefit from extended therapy include those with continued immobility or active cancer burden.

LMWH is also the preferred agent for extended therapy based on very limited evidence from experimental studies suggesting that LMWH may have antineoplastic effects and thus a survival advantage. However, in the setting of a recurrent VTE, there is very limited data on which to base the choice of extended treatment. Options include switching the therapeutic agent, increasing the dose or frequency of administration, or placement of an inferior vena cava filter. Consultation with a hematologist may also be warranted in this and more complicated scenarios.

Ultimately, LMWH appears to be the best available therapy for patients with a gynecologic malignancy. However, the decision to anticoagulate should be carefully planned out, taking into consideration the individual patient’s disease burden and associated comorbidities in order to select the most appropriate treatment option.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant financial disclosures.

Rudolph Virchow clearly demonstrated the association between malignancy and venous thromboembolic events. VTE – deep vein thrombosis and pulmonary embolism – affect between 15% and 38% of patients with gynecologic malignancies after surgery.

The rate of pulmonary embolism (PE) in this patient population can be as high as 6.8%, with the case fatality rate being 11%-12% (Obstet. Gynecol. 2012;119:155-67). Other factors associated with the development of VTE include prior VTE, older age, African American race, prolonged operative time, obesity, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of VTE in women undergoing gynecologic surgery is quadrupled in the presence of malignancy(Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE compared to matched controls (Gynecol. Oncol. 2007;106:439-45).

Additionally, cancer patients are typically older, have longer and more complex surgeries, and the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Although the treatment of VTE is fairly similar between patients with malignancy and those without cancer, treatment of a VTE in patients with cancer can be further complicated by higher VTE recurrence rates and increased risk of bleeding. Furthermore, issues related to the malignant disease process such as prognosis, presence and location of metastasis, and life expectancy should be taken into consideration when managing VTE in this patient population.

Generally, in the setting of an acute or recurrent VTE, initial therapy with a parenteral anticoagulant (heparin or low-molecular-weight heparins [LMWH]) should be immediately instituted in patients with a gynecologic malignancy, unless there is evidence of active bleeding or any other contraindication for the use of an anticoagulant.

Other factors associated with cancer such as immobilization, the presence of metastases, and impaired renal function with a creatinine clearance less than 30 mL/min, may increase the risk of bleeding complications but are not absolute contraindications to anticoagulation (Thromb. Haemost. 2008;100:435-9). The initial treatment phase, which last for 5-10 days, is then followed by a longer treatment phase lasting 3-6 months.

In the majority of cases, LMWH is the preferred agent for both the initial and prolonged treatment phase assuming adequate renal function. Based on evidence from a meta-analysis of 16 randomized controlled trials in cancer patients receiving initial anticoagulation for VTE, LMWH is associated with a 30% reduction in mortality without an increased risk of bleeding in comparison to unfractionated heparin (Cochrane Database. Syst. Rev. 2014;6:CD006649).

When compared with the vitamin K antagonist warfarin, LMWH appears to be associated with a significantly reduced rate of recurrent VTE (hazard ratio, 0.47; 95% confidence interval 0.32-0.71). However, this was not associated with a survival advantage (N. Engl. J. Med. 2003;349:146-53).

There are no trials comparing the different formulations of LMWH. In our practice, we routinely use the LMWH enoxaparin dosed at 1 mg/kg subcutaneously twice daily. Other well-studied LMWHs include dalteparin and tinzaparin.

LMWHs are primarily renally excreted, thus, in patients with compromised renal function, the biological half-life of the medication may be prolonged, leading to potential bleeding complications. The majority of LMWH trials excluded patients with creatinine clearance less than 30 mL/min, therefore, in patients with compromised renal function, one option would be to decrease the daily dose by as much as 50% and closely monitor antifactor XA levels. Alternatively, the use of unfractionated heparin in the acute setting followed by warfarin with close monitoring of the patient’s international normalized ratio could prove less cumbersome and ultimately safer for these patients. However, given the limitations of the currently available data we would not recommend the routine use of newer oral anticoagulation agents.

Patients with a malignancy are at increased risk for the development of a recurrent VTE even in the setting of anticoagulation. Some of the risks factors for this phenomenon include presence of central venous catheters, interruption of therapy for procedures, and immobilization. In cases of recurrent VTE, consideration should be given to extending the duration of treatment beyond the initial planned 3-6 months. Other patients that may benefit from extended therapy include those with continued immobility or active cancer burden.

LMWH is also the preferred agent for extended therapy based on very limited evidence from experimental studies suggesting that LMWH may have antineoplastic effects and thus a survival advantage. However, in the setting of a recurrent VTE, there is very limited data on which to base the choice of extended treatment. Options include switching the therapeutic agent, increasing the dose or frequency of administration, or placement of an inferior vena cava filter. Consultation with a hematologist may also be warranted in this and more complicated scenarios.

Ultimately, LMWH appears to be the best available therapy for patients with a gynecologic malignancy. However, the decision to anticoagulate should be carefully planned out, taking into consideration the individual patient’s disease burden and associated comorbidities in order to select the most appropriate treatment option.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant financial disclosures.

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

Sutures, hemoclips, and electrocautery are the primary means of achieving hemostasis during gynecologic surgery. When these are inadequate or infeasible, topical hemostatic agents can be employed. Use of these agents has increased by 10%-21% since 2000, yet studies evaluating their use in gynecologic surgery are limited (J. Surg. Res. 2014;186:458-66).

Oxidized regenerated cellulose

Oxidized regenerated cellulose (Surgicel) is made from dissolved oxidized cellulose woven into a dry gauze sheet (J. Urol. 2006;176:2367-74). It is applied directly to tissue, creating a scaffold for platelet aggregation and decreasing tissue pH, further activating the clotting cascade (Surg. Infect. (Larchmt.) 2003;4:255-62). It is absorbed in 14 days, but can persist for 1 year.

Oxidized regenerated cellulose (ORC) is easily passed through laparoscopic trocars. One study found ORC efficacious in controlling tubal hemorrhage during laparoscopic sterilization (Int. J. Gynaecol. Obstet. 2003;82:221-2). It has also been shown to have bactericidal activity (Surg. Infect. (Larchmt.) 2003; 4:255-62) and prevent development of peritoneal adhesions (Acta. Chir. Scand. 1978;144:375-8).

Microfibrillar collagen

Microfibrillar collagen (Avitene) is made from bovine collagen in a powder or sponge sheet, and acts as a scaffold for platelet aggregation. It is applied directly to tissue and is absorbed in 3 months. One study found microfibrillar collagen (MC) use during cold knife conization resulted in nonsignificant reduction in operative time and similar hemostatic results compared to Sturmdorf suture (Obstet. Gynecol. 1978;51:118-22). MC also has been used to treat bleeding following uterine perforation and during laparoscopic hysterectomy.

Gelatins

Gelatins (Gelfoam, Surgifoam) are made of porcine collagen in a powder or foam (J. Urol. 2006;176:2367-74). It is applied directly to tissue, acting as a sponge to absorb blood. Pressure for several minutes is necessary for optimal hemostasis. Some surgeons moisten gelatins with topical thrombin prior to use, though no trials exist evaluating the efficacy of this maneuver.

Gelatin is absorbed in 4-6 weeks (J. Urol. 2006;176:2367-74) and can be passed through laparoscopic trocars. No studies have evaluated gelatins in gynecologic surgery so its applications are extrapolated from vascular and urologic surgery (J. Urol. 2006;176:2367-74).

Microporous polysaccharide spheres

Microporous polysaccharide spheres (Arista) form a polysaccharide powder made from potato starch. It absorbs water, concentrating platelets and other proteins to accelerate clot formation. It is applied to a dry surgical field and followed with gentle pressure. MPS is absorbed in 48 hours. No studies specifically evaluate the use of MPS in gynecologic surgery.

Topical thrombins

Thrombin (Thrombin-JMI, Evithrom, Recothrom) is derived from bovine, human, or recombinant sources. It converts fibrinogen to fibrin and activates factor XIII, platelets, and smooth muscle constriction (Biologics 2008;2:593-9). Thrombin is a spray or syringe, and is often used with gelatin foam (Thrombi-Gel) or matrix (FloSeal) (Biologics 2008;2:593-9). FloSeal use has been reported during ovarian cystectomy (J. Minim. Invasive. Gynecol. 2009;16:153-6), hysterotomy repair (J. Obstet. Gynaecol. 2012;32:34-5). During myomectomy, it was associated with decreased blood loss, transfusions, and shorter length of stay (Fertil. Steril. 2009;92:356-60).

Fibrin sealants

Fibrin sealants (Tisseel, TachoSil) are made of thrombin and concentrated fibrinogen from human plasma. They must be mixed prior to application and act by forming a fibrin clot. Tisseel can reduce hemorrhage after loop electrosurgical excision procedure (Gynecol. Obstet. Invest. 2012;74:1-5) and decreases operative time, time to hemostasis, and blood loss during laparoscopic myomectomy (Surg. Endosc. 2012;26:2046-53). Case reports describe the use of fibrin sealants in the management of obstetrical hemorrhage and hysterotomy repair.

Cost and complications

Hemostatic agents vary significantly in cost, but no comparative cost analyses exist. One study found that commercial insurance was associated with topical hemostatic agent use during gynecologic surgery (J. Surg. Res. 2014;186:458-66).

Use of ORC has been associated with postoperative abscess and imitation of abscess without true infection, and MC and gelatins can also increase infection risk. The dry hemostatic agents have been associated with thromboembolism. The complications of thrombins and fibrins are related to immune responses or transmission of pathogens. Recombinant thrombin is believed to be the safest option (J. Am. Coll. Surg. 2007;205:256-65). Floseal has been reported to cause diffuse pelvic inflammation and postoperative small bowel obstruction. Because of possible complications, it is important to use only the needed amount of product, and to dictate use in the operative note.

Despite widespread use of topical hemostatic agents in gynecologic surgery, studies are limited and these agents should be recommended only as adjuncts to conventional methods of achieving hemostasis.

Topical hemostatic agents are recommended for surgical fields that are less amenable to electrocautery, including denuded areas on peritoneal surfaces, and around important heat-sensitive structures such as nerves. The dry matrix agents (ORC, MC, gelatin, and MPS) are most useful in slowly bleeding areas or in patients with a bleeding diathesis. Thrombin and fibrin can be useful in situations when more significant bleeding is encountered. Complications arising from topical hemostatic agents are few.

Given current limited studies, the choice of product continues to depend on patient characteristics and surgeon preference.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at UNC-Chapel Hill. Dr. Soper is a professor of gynecologic oncology at UNC-Chapel Hill.

Sutures, hemoclips, and electrocautery are the primary means of achieving hemostasis during gynecologic surgery. When these are inadequate or infeasible, topical hemostatic agents can be employed. Use of these agents has increased by 10%-21% since 2000, yet studies evaluating their use in gynecologic surgery are limited (J. Surg. Res. 2014;186:458-66).

Oxidized regenerated cellulose

Oxidized regenerated cellulose (Surgicel) is made from dissolved oxidized cellulose woven into a dry gauze sheet (J. Urol. 2006;176:2367-74). It is applied directly to tissue, creating a scaffold for platelet aggregation and decreasing tissue pH, further activating the clotting cascade (Surg. Infect. (Larchmt.) 2003;4:255-62). It is absorbed in 14 days, but can persist for 1 year.

Oxidized regenerated cellulose (ORC) is easily passed through laparoscopic trocars. One study found ORC efficacious in controlling tubal hemorrhage during laparoscopic sterilization (Int. J. Gynaecol. Obstet. 2003;82:221-2). It has also been shown to have bactericidal activity (Surg. Infect. (Larchmt.) 2003; 4:255-62) and prevent development of peritoneal adhesions (Acta. Chir. Scand. 1978;144:375-8).

Microfibrillar collagen

Microfibrillar collagen (Avitene) is made from bovine collagen in a powder or sponge sheet, and acts as a scaffold for platelet aggregation. It is applied directly to tissue and is absorbed in 3 months. One study found microfibrillar collagen (MC) use during cold knife conization resulted in nonsignificant reduction in operative time and similar hemostatic results compared to Sturmdorf suture (Obstet. Gynecol. 1978;51:118-22). MC also has been used to treat bleeding following uterine perforation and during laparoscopic hysterectomy.

Gelatins

Gelatins (Gelfoam, Surgifoam) are made of porcine collagen in a powder or foam (J. Urol. 2006;176:2367-74). It is applied directly to tissue, acting as a sponge to absorb blood. Pressure for several minutes is necessary for optimal hemostasis. Some surgeons moisten gelatins with topical thrombin prior to use, though no trials exist evaluating the efficacy of this maneuver.

Gelatin is absorbed in 4-6 weeks (J. Urol. 2006;176:2367-74) and can be passed through laparoscopic trocars. No studies have evaluated gelatins in gynecologic surgery so its applications are extrapolated from vascular and urologic surgery (J. Urol. 2006;176:2367-74).

Microporous polysaccharide spheres

Microporous polysaccharide spheres (Arista) form a polysaccharide powder made from potato starch. It absorbs water, concentrating platelets and other proteins to accelerate clot formation. It is applied to a dry surgical field and followed with gentle pressure. MPS is absorbed in 48 hours. No studies specifically evaluate the use of MPS in gynecologic surgery.

Topical thrombins

Thrombin (Thrombin-JMI, Evithrom, Recothrom) is derived from bovine, human, or recombinant sources. It converts fibrinogen to fibrin and activates factor XIII, platelets, and smooth muscle constriction (Biologics 2008;2:593-9). Thrombin is a spray or syringe, and is often used with gelatin foam (Thrombi-Gel) or matrix (FloSeal) (Biologics 2008;2:593-9). FloSeal use has been reported during ovarian cystectomy (J. Minim. Invasive. Gynecol. 2009;16:153-6), hysterotomy repair (J. Obstet. Gynaecol. 2012;32:34-5). During myomectomy, it was associated with decreased blood loss, transfusions, and shorter length of stay (Fertil. Steril. 2009;92:356-60).

Fibrin sealants

Fibrin sealants (Tisseel, TachoSil) are made of thrombin and concentrated fibrinogen from human plasma. They must be mixed prior to application and act by forming a fibrin clot. Tisseel can reduce hemorrhage after loop electrosurgical excision procedure (Gynecol. Obstet. Invest. 2012;74:1-5) and decreases operative time, time to hemostasis, and blood loss during laparoscopic myomectomy (Surg. Endosc. 2012;26:2046-53). Case reports describe the use of fibrin sealants in the management of obstetrical hemorrhage and hysterotomy repair.

Cost and complications

Hemostatic agents vary significantly in cost, but no comparative cost analyses exist. One study found that commercial insurance was associated with topical hemostatic agent use during gynecologic surgery (J. Surg. Res. 2014;186:458-66).

Use of ORC has been associated with postoperative abscess and imitation of abscess without true infection, and MC and gelatins can also increase infection risk. The dry hemostatic agents have been associated with thromboembolism. The complications of thrombins and fibrins are related to immune responses or transmission of pathogens. Recombinant thrombin is believed to be the safest option (J. Am. Coll. Surg. 2007;205:256-65). Floseal has been reported to cause diffuse pelvic inflammation and postoperative small bowel obstruction. Because of possible complications, it is important to use only the needed amount of product, and to dictate use in the operative note.

Despite widespread use of topical hemostatic agents in gynecologic surgery, studies are limited and these agents should be recommended only as adjuncts to conventional methods of achieving hemostasis.

Topical hemostatic agents are recommended for surgical fields that are less amenable to electrocautery, including denuded areas on peritoneal surfaces, and around important heat-sensitive structures such as nerves. The dry matrix agents (ORC, MC, gelatin, and MPS) are most useful in slowly bleeding areas or in patients with a bleeding diathesis. Thrombin and fibrin can be useful in situations when more significant bleeding is encountered. Complications arising from topical hemostatic agents are few.

Given current limited studies, the choice of product continues to depend on patient characteristics and surgeon preference.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at UNC-Chapel Hill. Dr. Soper is a professor of gynecologic oncology at UNC-Chapel Hill.

Sutures, hemoclips, and electrocautery are the primary means of achieving hemostasis during gynecologic surgery. When these are inadequate or infeasible, topical hemostatic agents can be employed. Use of these agents has increased by 10%-21% since 2000, yet studies evaluating their use in gynecologic surgery are limited (J. Surg. Res. 2014;186:458-66).

Oxidized regenerated cellulose

Oxidized regenerated cellulose (Surgicel) is made from dissolved oxidized cellulose woven into a dry gauze sheet (J. Urol. 2006;176:2367-74). It is applied directly to tissue, creating a scaffold for platelet aggregation and decreasing tissue pH, further activating the clotting cascade (Surg. Infect. (Larchmt.) 2003;4:255-62). It is absorbed in 14 days, but can persist for 1 year.

Oxidized regenerated cellulose (ORC) is easily passed through laparoscopic trocars. One study found ORC efficacious in controlling tubal hemorrhage during laparoscopic sterilization (Int. J. Gynaecol. Obstet. 2003;82:221-2). It has also been shown to have bactericidal activity (Surg. Infect. (Larchmt.) 2003; 4:255-62) and prevent development of peritoneal adhesions (Acta. Chir. Scand. 1978;144:375-8).

Microfibrillar collagen

Microfibrillar collagen (Avitene) is made from bovine collagen in a powder or sponge sheet, and acts as a scaffold for platelet aggregation. It is applied directly to tissue and is absorbed in 3 months. One study found microfibrillar collagen (MC) use during cold knife conization resulted in nonsignificant reduction in operative time and similar hemostatic results compared to Sturmdorf suture (Obstet. Gynecol. 1978;51:118-22). MC also has been used to treat bleeding following uterine perforation and during laparoscopic hysterectomy.

Gelatins

Gelatins (Gelfoam, Surgifoam) are made of porcine collagen in a powder or foam (J. Urol. 2006;176:2367-74). It is applied directly to tissue, acting as a sponge to absorb blood. Pressure for several minutes is necessary for optimal hemostasis. Some surgeons moisten gelatins with topical thrombin prior to use, though no trials exist evaluating the efficacy of this maneuver.

Gelatin is absorbed in 4-6 weeks (J. Urol. 2006;176:2367-74) and can be passed through laparoscopic trocars. No studies have evaluated gelatins in gynecologic surgery so its applications are extrapolated from vascular and urologic surgery (J. Urol. 2006;176:2367-74).

Microporous polysaccharide spheres

Microporous polysaccharide spheres (Arista) form a polysaccharide powder made from potato starch. It absorbs water, concentrating platelets and other proteins to accelerate clot formation. It is applied to a dry surgical field and followed with gentle pressure. MPS is absorbed in 48 hours. No studies specifically evaluate the use of MPS in gynecologic surgery.

Topical thrombins

Thrombin (Thrombin-JMI, Evithrom, Recothrom) is derived from bovine, human, or recombinant sources. It converts fibrinogen to fibrin and activates factor XIII, platelets, and smooth muscle constriction (Biologics 2008;2:593-9). Thrombin is a spray or syringe, and is often used with gelatin foam (Thrombi-Gel) or matrix (FloSeal) (Biologics 2008;2:593-9). FloSeal use has been reported during ovarian cystectomy (J. Minim. Invasive. Gynecol. 2009;16:153-6), hysterotomy repair (J. Obstet. Gynaecol. 2012;32:34-5). During myomectomy, it was associated with decreased blood loss, transfusions, and shorter length of stay (Fertil. Steril. 2009;92:356-60).

Fibrin sealants

Fibrin sealants (Tisseel, TachoSil) are made of thrombin and concentrated fibrinogen from human plasma. They must be mixed prior to application and act by forming a fibrin clot. Tisseel can reduce hemorrhage after loop electrosurgical excision procedure (Gynecol. Obstet. Invest. 2012;74:1-5) and decreases operative time, time to hemostasis, and blood loss during laparoscopic myomectomy (Surg. Endosc. 2012;26:2046-53). Case reports describe the use of fibrin sealants in the management of obstetrical hemorrhage and hysterotomy repair.

Cost and complications

Hemostatic agents vary significantly in cost, but no comparative cost analyses exist. One study found that commercial insurance was associated with topical hemostatic agent use during gynecologic surgery (J. Surg. Res. 2014;186:458-66).

Use of ORC has been associated with postoperative abscess and imitation of abscess without true infection, and MC and gelatins can also increase infection risk. The dry hemostatic agents have been associated with thromboembolism. The complications of thrombins and fibrins are related to immune responses or transmission of pathogens. Recombinant thrombin is believed to be the safest option (J. Am. Coll. Surg. 2007;205:256-65). Floseal has been reported to cause diffuse pelvic inflammation and postoperative small bowel obstruction. Because of possible complications, it is important to use only the needed amount of product, and to dictate use in the operative note.

Despite widespread use of topical hemostatic agents in gynecologic surgery, studies are limited and these agents should be recommended only as adjuncts to conventional methods of achieving hemostasis.

Topical hemostatic agents are recommended for surgical fields that are less amenable to electrocautery, including denuded areas on peritoneal surfaces, and around important heat-sensitive structures such as nerves. The dry matrix agents (ORC, MC, gelatin, and MPS) are most useful in slowly bleeding areas or in patients with a bleeding diathesis. Thrombin and fibrin can be useful in situations when more significant bleeding is encountered. Complications arising from topical hemostatic agents are few.

Given current limited studies, the choice of product continues to depend on patient characteristics and surgeon preference.

Dr. Wysham is currently a fellow in the department of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at UNC-Chapel Hill. Dr. Soper is a professor of gynecologic oncology at UNC-Chapel Hill.

The majority of women with gynecologic cancer will undergo surgery for their disease. Deep vein thrombosis and pulmonary embolism, or venous thromboembolic events are common, serious complications. The rate of pulmonary embolism in women with gynecologic malignancy may be as high as 6.8%, with the case fatality rate being 11%-12%. Hence, one key strategy to lower the rate of fatal pulmonary embolism depends on proper prophylaxis for deep vein thrombosis prevention.

Factors associated with the development of venous thromboembolic events (VTE) include prior VTE, malignancy, older age, African American race, prolonged operative time, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of pulmonary embolism (PE) in women undergoing gynecologic surgery is quadrupled in the presence of malignancy (Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE, compared with matched controls (Gynecol. Oncol. 2007;106:439-45). In addition, cancer patients are typically older and have longer and more complex surgeries. Furthermore, the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Other risk factors associated with the development of VTE include hormone replacement therapy, oral contraceptives, use of tamoxifen, and inherited thrombophilias. The most common is factor V Leiden deficiency, affecting up to 20% of patients with VTE. Affected heterozygotes have a 3- to 8-fold increased risk of VTE, whereas homozygotes have a 50- to 80-fold increased risk (Blood 1995;85:1504-8).

Depending on additional risk factors, both the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin and guidelines published by the American College of Chest Physicians (ACCP) place women with gynecologic cancers into "high" or "highest" risk categories (Obstet. Gynecol. 2007;110:429-40; Chest 2012;141:e227S-77S).

Currently, thromboprophylaxis regimens include mechanical and pharmacologic methods. Mechanical devices include graduated compression stockings and intermittent pneumatic compression, which reduce venous stasis and may promote endogenous fibrinolysis. Pharmacologic prophylaxis includes unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Prospective controlled trials have shown that UFH reduces VTE in patients with gynecologic cancer. Trials comparing LMWH with UFH have demonstrated equivalent efficacy and similar bleeding complications. The recommended prophylactic dose for LMWH is 40 mg subcutaneous injection daily. However, this dose may need to be adjusted in morbidly obese patients (body mass index greater than 40 kg/m²) as well as in women with abnormal renal clearance. UFH should be administered as a dose of 5,000 units subcutaneously three times daily. Intermittent pneumatic compression also has been shown to reduce the incidence of VTE in this patient population.

A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients, such as women with gynecologic cancer. Although limited data exist to support this approach in gynecology patients, studies from other surgical disciplines suggest benefit from a combined regimen. With regards to addressing the timing of initiation, a large retrospective trial of patients undergoing hysterectomy for benign indications concluded that postoperative rather than preoperative administration of UFH or LMWH may reduce the risk of bleeding complications without apparent risk of increased VTE (Acta. Obstet. Gynecol. Scand. 2008;87:1039-47).

In summary, the majority of gynecologic oncology patients are considered to be at the highest risk for developing VTE. For this group of women, double prophylaxis with either UFH or LMWH, and a mechanical method (intermittent pneumatic compression) are recommended in the perioperative setting. In addition, ACCP further recommends that these patients receive extended postoperative prophylaxis with LMWH for 4 weeks. Further evidence is needed to determine acceptable timing for initiation of therapy in order to find a balance between adequate thromboprophylaxis and bleeding complications.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant disclosures. Scan this QR code or go to obgynnews.com to view similar columns.

The majority of women with gynecologic cancer will undergo surgery for their disease. Deep vein thrombosis and pulmonary embolism, or venous thromboembolic events are common, serious complications. The rate of pulmonary embolism in women with gynecologic malignancy may be as high as 6.8%, with the case fatality rate being 11%-12%. Hence, one key strategy to lower the rate of fatal pulmonary embolism depends on proper prophylaxis for deep vein thrombosis prevention.

Factors associated with the development of venous thromboembolic events (VTE) include prior VTE, malignancy, older age, African American race, prolonged operative time, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of pulmonary embolism (PE) in women undergoing gynecologic surgery is quadrupled in the presence of malignancy (Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE, compared with matched controls (Gynecol. Oncol. 2007;106:439-45). In addition, cancer patients are typically older and have longer and more complex surgeries. Furthermore, the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Other risk factors associated with the development of VTE include hormone replacement therapy, oral contraceptives, use of tamoxifen, and inherited thrombophilias. The most common is factor V Leiden deficiency, affecting up to 20% of patients with VTE. Affected heterozygotes have a 3- to 8-fold increased risk of VTE, whereas homozygotes have a 50- to 80-fold increased risk (Blood 1995;85:1504-8).

Depending on additional risk factors, both the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin and guidelines published by the American College of Chest Physicians (ACCP) place women with gynecologic cancers into "high" or "highest" risk categories (Obstet. Gynecol. 2007;110:429-40; Chest 2012;141:e227S-77S).

Currently, thromboprophylaxis regimens include mechanical and pharmacologic methods. Mechanical devices include graduated compression stockings and intermittent pneumatic compression, which reduce venous stasis and may promote endogenous fibrinolysis. Pharmacologic prophylaxis includes unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Prospective controlled trials have shown that UFH reduces VTE in patients with gynecologic cancer. Trials comparing LMWH with UFH have demonstrated equivalent efficacy and similar bleeding complications. The recommended prophylactic dose for LMWH is 40 mg subcutaneous injection daily. However, this dose may need to be adjusted in morbidly obese patients (body mass index greater than 40 kg/m²) as well as in women with abnormal renal clearance. UFH should be administered as a dose of 5,000 units subcutaneously three times daily. Intermittent pneumatic compression also has been shown to reduce the incidence of VTE in this patient population.

A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients, such as women with gynecologic cancer. Although limited data exist to support this approach in gynecology patients, studies from other surgical disciplines suggest benefit from a combined regimen. With regards to addressing the timing of initiation, a large retrospective trial of patients undergoing hysterectomy for benign indications concluded that postoperative rather than preoperative administration of UFH or LMWH may reduce the risk of bleeding complications without apparent risk of increased VTE (Acta. Obstet. Gynecol. Scand. 2008;87:1039-47).

In summary, the majority of gynecologic oncology patients are considered to be at the highest risk for developing VTE. For this group of women, double prophylaxis with either UFH or LMWH, and a mechanical method (intermittent pneumatic compression) are recommended in the perioperative setting. In addition, ACCP further recommends that these patients receive extended postoperative prophylaxis with LMWH for 4 weeks. Further evidence is needed to determine acceptable timing for initiation of therapy in order to find a balance between adequate thromboprophylaxis and bleeding complications.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant disclosures. Scan this QR code or go to obgynnews.com to view similar columns.

The majority of women with gynecologic cancer will undergo surgery for their disease. Deep vein thrombosis and pulmonary embolism, or venous thromboembolic events are common, serious complications. The rate of pulmonary embolism in women with gynecologic malignancy may be as high as 6.8%, with the case fatality rate being 11%-12%. Hence, one key strategy to lower the rate of fatal pulmonary embolism depends on proper prophylaxis for deep vein thrombosis prevention.

Factors associated with the development of venous thromboembolic events (VTE) include prior VTE, malignancy, older age, African American race, prolonged operative time, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of pulmonary embolism (PE) in women undergoing gynecologic surgery is quadrupled in the presence of malignancy (Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE, compared with matched controls (Gynecol. Oncol. 2007;106:439-45). In addition, cancer patients are typically older and have longer and more complex surgeries. Furthermore, the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).

Other risk factors associated with the development of VTE include hormone replacement therapy, oral contraceptives, use of tamoxifen, and inherited thrombophilias. The most common is factor V Leiden deficiency, affecting up to 20% of patients with VTE. Affected heterozygotes have a 3- to 8-fold increased risk of VTE, whereas homozygotes have a 50- to 80-fold increased risk (Blood 1995;85:1504-8).

Depending on additional risk factors, both the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin and guidelines published by the American College of Chest Physicians (ACCP) place women with gynecologic cancers into "high" or "highest" risk categories (Obstet. Gynecol. 2007;110:429-40; Chest 2012;141:e227S-77S).

Currently, thromboprophylaxis regimens include mechanical and pharmacologic methods. Mechanical devices include graduated compression stockings and intermittent pneumatic compression, which reduce venous stasis and may promote endogenous fibrinolysis. Pharmacologic prophylaxis includes unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Prospective controlled trials have shown that UFH reduces VTE in patients with gynecologic cancer. Trials comparing LMWH with UFH have demonstrated equivalent efficacy and similar bleeding complications. The recommended prophylactic dose for LMWH is 40 mg subcutaneous injection daily. However, this dose may need to be adjusted in morbidly obese patients (body mass index greater than 40 kg/m²) as well as in women with abnormal renal clearance. UFH should be administered as a dose of 5,000 units subcutaneously three times daily. Intermittent pneumatic compression also has been shown to reduce the incidence of VTE in this patient population.

A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients, such as women with gynecologic cancer. Although limited data exist to support this approach in gynecology patients, studies from other surgical disciplines suggest benefit from a combined regimen. With regards to addressing the timing of initiation, a large retrospective trial of patients undergoing hysterectomy for benign indications concluded that postoperative rather than preoperative administration of UFH or LMWH may reduce the risk of bleeding complications without apparent risk of increased VTE (Acta. Obstet. Gynecol. Scand. 2008;87:1039-47).

In summary, the majority of gynecologic oncology patients are considered to be at the highest risk for developing VTE. For this group of women, double prophylaxis with either UFH or LMWH, and a mechanical method (intermittent pneumatic compression) are recommended in the perioperative setting. In addition, ACCP further recommends that these patients receive extended postoperative prophylaxis with LMWH for 4 weeks. Further evidence is needed to determine acceptable timing for initiation of therapy in order to find a balance between adequate thromboprophylaxis and bleeding complications.

Dr. Roque is a fellow in the gynecologic oncology program 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. Roque and Dr. Clarke-Pearson said they had no relevant disclosures. Scan this QR code or go to obgynnews.com to view similar columns.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

Most practicing gynecologists will diagnose a patient with endometrial cancer at some point during their careers. While referral to a gynecologic oncologist is indicated for treatment of all endometrial cancers, patients will likely have questions for their gynecologists prior to referral. The backbone of prognosis and treatment depends on the type of endometrial cancer (type 1 or type 2) and the stage of the cancer. The basics of endometrial cancer treatment will be reviewed in this article.

Endometrial cancer can be classified into two distinct subgroups based on histology and clinical behavior. Type 1 tumors are the most common type of endometrial cancer, accounting for nearly 80% of endometrial cancers. These tumors have an endometrioid histology and are well-differentiated, gland-forming tumors. The endometrioid tumors are graded by evaluating the gland formation and/or architecture, with grade 1 tumors having less than 5% solid growth and grade 2 tumors having 6%-50% solid growth. They also are graded based on the degree of nuclear atypia (Gynecol. Oncol. 1983;15:10-17).

Type 1 tumors are estrogen driven and less aggressive than their type 2 counterparts. They tend to be more common in overweight or obese patients, patients with longstanding anovulation or polycystic ovarian syndrome (PCOS), or patients placed on unopposed estrogen. Molecularly, type 1 tumors often exhibit mutations in phosphatase and tensin homolog (PTEN), Kras, and beta-catenin. Microsatellite instability with mutations in MSH2, MSH6, MLH1, and PMS2 also has been observed in 20% of sporadic endometrial cancers, as well as women with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome) (J. Clin. Oncol. 2006;24:4783-91).

Type 1 tumors are starkly different from type 2 tumors. While type 2 tumors account for 10%-20% of endometrial cancers, they are responsible for the majority of recurrences and deaths. They include serous, clear cell, mucinous, squamous, transitional cell, carcinosarcomas and undifferentiated tumors. More recently, it has been suggested that grade 3 endometrioid carcinomas be grouped with type 2 tumors. The genetic mutations and clinical behavior of grade 3 endometrioid tumors are more consistent with type 2 tumors. Type 2 tumors are more likely to show mutations in p53, aneuploidy, and overexpression of HER2/neu (Gynecol. Oncol. 2008;108:3-9). Type 2 tumors are more likely to present with advanced stage.

While it is important to understand these two categories of endometrial cancers as two distinct clinical entities with markedly different prognosis and outcomes, there is some histologic crossover. Some endometrioid tumors will have a component of serous or clear cell within the tumor. Investigators have found that up to a 10% serous component within an endometrioid tumor can confer a worse prognosis and likely warrants more aggressive treatment (Cancer 2004;101:2214-21).

Given the relatively indolent clinical course of type 1 tumors, preoperative imaging to evaluate for metastatic disease is not indicated without concerning symptoms. Additionally, often women diagnosed with type 1 tumors are able to be fully treated with hysterectomy, and in circumstances of early-stage disease, most patients with these tumors do not need adjuvant treatment with chemotherapy or radiation. Alternatively, type 2 tumors are more aggressive and may warrant additional imaging prior to hysterectomy to evaluate for distant metastasis, as uterine features may not be indicative of metastatic disease. These women will need additional treatment with radiation and likely chemotherapy following comprehensive surgical staging and hysterectomy, given the aggressive nature of their tumors.

Dividing endometrial cancers into these two distinct groups allows providers to appropriately counsel and treat patients. Having an understanding of this distinction can help practicing gynecologists who will most likely make the diagnosis of endometrial cancer within their practice. Any patient with abnormal bleeding or postmenopausal bleeding should be promptly evaluated to facilitate an early diagnosis. Regardless of whether a patient has a type 1 or type 2 tumor, early-stage diagnosis will improve the patient’s prognosis and survival.

Dr. Clark is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Clark and Dr. Gehrig had no conflicts of interest to disclose.

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.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. 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. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. 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. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

With the increasing use of ultrasound in the first trimester, asymptomatic adnexal masses are being diagnosed earlier in pregnancy, leaving providers with an often difficult clinical scenario. The reported incidence of adnexal masses ranges from 1 in 81 to 1 in 8,000 pregnancies, and 0.93%-6% of these are malignant (Gynecol. Oncol. 2006;101:315-21; Am. J. Obstet. Gynecol. 1999;181:19-24). In light of this, the importance of recognizing adnexal masses and knowledge of their management are crucial for any practicing obstetrician gynecologist.

Differential diagnosis

In pregnancy, the majority of adnexal masses are benign simple cysts less than 5 cm (BJOG 2003;110:578-83). As such, the majority of masses (probable corpus luteum cysts) detected in the first trimester (70% in one study) will resolve by the early part of the second trimester (Clin. Obstet. Gynecol. 2006;49:492-505). Adnexal masses are commonly physiologic or functional cysts. Benign masses with complex features can include corpus luteum, mature teratomas, hydrosalpinx, theca lutein cysts, or endometriomas. Complex adnexal masses greater than 5 cm are most likely mature teratomas (Am. J. Obstet. Gynecol. 2001;184:1504-12). Degenerating or pedunculated fibroids can mimic an adnexal mass and may cause pain, clouding the diagnosis.

Of the rare malignant lesions that occur in pregnancy, approximately half are epithelial tumors and one-third are germ cell tumors. Of the epithelial neoplasms, up to 50% may be low-malignant-potential tumors.

Diagnostic evaluation

Imaging: Transvaginal ultrasound is regarded as the modality of choice when evaluating adnexal pathology. Abdominal ultrasound may be especially helpful when the ovaries are outside of the pelvis, especially later in gestation. MRI without contrast may aid in distinguishing leiomyoma and ovarian pathology, which is vital when planning surgery. However, MRI with gadolinium is not recommended as its safety in pregnancy has not been established.

Tumor markers: None of the available tumor markers may be reliably used to diagnose ovarian cancer in pregnancy. CA-125 is elevated in epithelial ovarian cancer, but it is also elevated in pregnancy. However, significant elevations (greater than 1,000 U/mL) are more likely to be associated with cancer.

Markers for germ cell tumors include alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Maternal serum levels of AFP (MSAFP) normally rise in pregnancy, although extreme values (less than 500 ng/mL) are associated with neural tube defects while levels greater than 1,000 ng/mL may be associated with an ovarian germ cell tumor (especially when greater than 10,000 ng/mL). LDH is elevated in women with ovarian dysgerminomas and is reliable in pregnancy outside of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Of course, hCG is elevated in pregnancy, negating its value as a germ cell tumor marker. Inhibin B may be elevated in association with granulosa cell tumors; however, it is also elevated in early gestation.

Management

Because most corpus luteum will resolve, it is recommended to electively resect adnexal masses in the second trimester when they meet the following criteria: lesions are greater than 10 cm in diameter; they are complex lesions (Fertil. Steril. 2009;91:1895-902; Obstet. Gynecol. 1999;93:585-9).

Benign-appearing but persistent simple cysts in the second trimester may be managed conservatively, as approximately 70% will resolve. Thus, routine removal of persistent cysts is not recommended (BJOG 2003;110:578-83). Risk factors for persistent lesions include size greater than 5 cm and complex morphology (Obstet. Gynecol. 1999;93:585-9).Providers may consider serial ultrasounds of ovarian cysts to detect an increase in size or change in character that may warrant further investigation.

Surgery is considered in asymptomatic women meeting the above criteria, to diagnose malignancy or reduce the risk of torsion or rupture. Torsion has been found to be more likely in the late first and early second trimester, with only 6% occurring after 20 weeks. Corpus luteum cysts may on occasion persist into the second trimester and can account for up to 17% of all cystic adnexal masses (Am. J. Obstet. Gynecol. 1999;181:19-24). It is important to remember that if a corpus luteum is surgically resected in the first trimester, progesterone needs to be replaced to avoid pregnancy loss. Of those complex lesions diagnosed in the first trimester that persist into the second trimester, up to 10% may be malignant.

Providers who feel comfortable with laparoscopic techniques can proceed with minimally invasive surgery, with optimal timing in the early second trimester (J. Minim. Invasive Gynecol. 2011;18:720-5). Care should be taken to consider fundal height when choosing trocar placement. If there is a high suspicion for malignancy, providers may want to proceed via laparotomy, which should be via a vertical midline incision. Tocolytic therapy given prophylactically at the time of surgery has no proven benefit and should not be routinely administered.

Washings should be obtained and providers should perform a thorough inspection of the abdomen, contralateral ovary, omentum, and peritoneal surfaces. Any suspicious lesions should be biopsied. A simple cystectomy is reasonable with benign lesions; however, a unilateral salpingo-oophorectomy should be performed with frozen confirmation if there are any concerning findings for malignancy. If a malignancy is confirmed, a gynecologic oncologist should be consulted, and surgical staging should be considered.

Dr. Sullivan is a chief resident in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. 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. Sullivan, Dr. Gehrig, and Dr. Clarke-Pearson said they had no relevant financial disclosures.

Because of the increased risks associated with surgery in an elderly population, a thorough preoperative assessment should include identification of medical problems and important risk factors for increased perioperative morbidity and mortality, a thorough evaluation of the patient’s activities of daily living, and a mini–mental status exam (Primary Care 1989;16:361-76).

The severity of a patient’s illness is a better predictor of perioperative morbidity than age, and therefore age alone should not determine whether gynecologists operate (Clin. Podiatr. Med. Surg. 2003;20:607-26). In elderly patients, we should consider preoperative consultation with the patient’s primary care physician, subspecialists, geriatricians, physical and occupational therapists, and anesthesiologist to evaluate comorbidities and optimize preoperative status. Posthospitalization discharge planning also should start preoperatively if there is a concern that a patient may not be able to be discharged home.

Gynecologists also should consider the indications for surgery and a patient’s life expectancy. Prior to surgery, surgeons should believe that each patient has an expected life span such that they will benefit from the surgery. We should perform the most appropriate and least aggressive surgery and take into consideration the duration of the procedure. Surgeons also should consider functional outcomes, including quality of life, and the goal should be a postoperative return to normal function (Mt. Sinai J. Med. 2012;79:95-106).

Other factors to consider once a gynecologist has decided to operate on an elderly patient include surgical approach, mode of anesthesia, and the need for operative staging. An abdominal surgery is a risk factor for perioperative morbidity. Therefore, a laparoscopic or vaginal approach should be considered in elderly patients. These surgeries may promote more rapid return to functional status, thereby decreasing the risk of postoperative respiratory complications, length of hospital stay, and risk of delirium and postoperative cognitive decline (Curr. Opin. Obstet. Gynecol. 1997;9:300-305).Unfortunately, changes in cardiovascular physiology during abdominal insufflation and desufflation may lead to decreased peripheral perfusion and increased cardiac output. Additionally, a laparoscopic approach can lead to increases in operating time. Therefore, a gynecologist must carefully consider surgical approach.

Another important aspect to consider prior to surgery is whether the procedure can be performed under neuraxial anesthesia. An epidural could be left in place for postoperative pain control and eliminate the need for general anesthesia and postoperative pain control with narcotics. Gynecologic oncologists specifically must consider whether extending the procedure to include surgical staging is necessary and appropriate for each individual patient. A specific example concerns lymph node dissection in endometrial cancer. A recent study has shown that 5-year survival does not differ in women older than 80 years with low-grade endometrial cancer if lymph node dissection is omitted (Gynecol. Oncol. 2012;126:12-15).This may be important in limiting total anesthetic time to under 3 hours in an attempt to decrease perioperative morbidity and mortality.

Specific operating room considerations include patient position, coverage, and orientation. Elderly patients have fragile skin with decreased elasticity and decreased muscle mass. Therefore, they are more sensitive than their younger counterparts to bruising, skin tears, pressure ulcers, and hypothermia. Extra care must be taken during patient positioning to pad joints, avoid tape on fragile skin, and keep her covered with blankets or a warming device. Elderly patients also are at increased risk for venous thromboembolism; therefore sequential compression devices and, potentially, chemoprophylaxis should be used intraoperatively. On emergence from anesthesia, elderly patients should be given their glasses, and operating room staff should speak clearly and loudly to orient the patient to their situation.

Postoperatively, providers and family should continue to orient and reorient elderly patients to person, place, and situation. Good pain control is important, especially with larger abdominal incisions, to decrease respiratory complications and promote early ambulation. NSAIDs or neuraxial anesthesia should be considered to decrease the use of potentially sedating opioids. But avoid NSAIDs in patients with dehydration, congestive heart failure, and preexisting renal disease. It also is important to get patients back to their activities of daily living as soon as possible; therefore inpatient physical and occupational therapy should be considered on the day following surgery. Prior to discharge, care to avoid too many additional medications and attention to potential medication interactions are critical.

Elderly women are at risk for increased postoperative morbidity and mortality; however, with appropriate perioperative planning, these risks can be minimized. Each patient and her situation should be carefully evaluated, and a multidisciplinary team assembled to assist with taking the steps necessary to promote a smooth transition to the outpatient setting and decrease complications.

Dr. Hacker is a rising fourth-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. E-mail them at obnews@frontlinemedcom.com.

Because of the increased risks associated with surgery in an elderly population, a thorough preoperative assessment should include identification of medical problems and important risk factors for increased perioperative morbidity and mortality, a thorough evaluation of the patient’s activities of daily living, and a mini–mental status exam (Primary Care 1989;16:361-76).

The severity of a patient’s illness is a better predictor of perioperative morbidity than age, and therefore age alone should not determine whether gynecologists operate (Clin. Podiatr. Med. Surg. 2003;20:607-26). In elderly patients, we should consider preoperative consultation with the patient’s primary care physician, subspecialists, geriatricians, physical and occupational therapists, and anesthesiologist to evaluate comorbidities and optimize preoperative status. Posthospitalization discharge planning also should start preoperatively if there is a concern that a patient may not be able to be discharged home.

Gynecologists also should consider the indications for surgery and a patient’s life expectancy. Prior to surgery, surgeons should believe that each patient has an expected life span such that they will benefit from the surgery. We should perform the most appropriate and least aggressive surgery and take into consideration the duration of the procedure. Surgeons also should consider functional outcomes, including quality of life, and the goal should be a postoperative return to normal function (Mt. Sinai J. Med. 2012;79:95-106).

Other factors to consider once a gynecologist has decided to operate on an elderly patient include surgical approach, mode of anesthesia, and the need for operative staging. An abdominal surgery is a risk factor for perioperative morbidity. Therefore, a laparoscopic or vaginal approach should be considered in elderly patients. These surgeries may promote more rapid return to functional status, thereby decreasing the risk of postoperative respiratory complications, length of hospital stay, and risk of delirium and postoperative cognitive decline (Curr. Opin. Obstet. Gynecol. 1997;9:300-305).Unfortunately, changes in cardiovascular physiology during abdominal insufflation and desufflation may lead to decreased peripheral perfusion and increased cardiac output. Additionally, a laparoscopic approach can lead to increases in operating time. Therefore, a gynecologist must carefully consider surgical approach.

Another important aspect to consider prior to surgery is whether the procedure can be performed under neuraxial anesthesia. An epidural could be left in place for postoperative pain control and eliminate the need for general anesthesia and postoperative pain control with narcotics. Gynecologic oncologists specifically must consider whether extending the procedure to include surgical staging is necessary and appropriate for each individual patient. A specific example concerns lymph node dissection in endometrial cancer. A recent study has shown that 5-year survival does not differ in women older than 80 years with low-grade endometrial cancer if lymph node dissection is omitted (Gynecol. Oncol. 2012;126:12-15).This may be important in limiting total anesthetic time to under 3 hours in an attempt to decrease perioperative morbidity and mortality.

Specific operating room considerations include patient position, coverage, and orientation. Elderly patients have fragile skin with decreased elasticity and decreased muscle mass. Therefore, they are more sensitive than their younger counterparts to bruising, skin tears, pressure ulcers, and hypothermia. Extra care must be taken during patient positioning to pad joints, avoid tape on fragile skin, and keep her covered with blankets or a warming device. Elderly patients also are at increased risk for venous thromboembolism; therefore sequential compression devices and, potentially, chemoprophylaxis should be used intraoperatively. On emergence from anesthesia, elderly patients should be given their glasses, and operating room staff should speak clearly and loudly to orient the patient to their situation.

Postoperatively, providers and family should continue to orient and reorient elderly patients to person, place, and situation. Good pain control is important, especially with larger abdominal incisions, to decrease respiratory complications and promote early ambulation. NSAIDs or neuraxial anesthesia should be considered to decrease the use of potentially sedating opioids. But avoid NSAIDs in patients with dehydration, congestive heart failure, and preexisting renal disease. It also is important to get patients back to their activities of daily living as soon as possible; therefore inpatient physical and occupational therapy should be considered on the day following surgery. Prior to discharge, care to avoid too many additional medications and attention to potential medication interactions are critical.

Elderly women are at risk for increased postoperative morbidity and mortality; however, with appropriate perioperative planning, these risks can be minimized. Each patient and her situation should be carefully evaluated, and a multidisciplinary team assembled to assist with taking the steps necessary to promote a smooth transition to the outpatient setting and decrease complications.

Dr. Hacker is a rising fourth-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. E-mail them at obnews@frontlinemedcom.com.

Because of the increased risks associated with surgery in an elderly population, a thorough preoperative assessment should include identification of medical problems and important risk factors for increased perioperative morbidity and mortality, a thorough evaluation of the patient’s activities of daily living, and a mini–mental status exam (Primary Care 1989;16:361-76).

The severity of a patient’s illness is a better predictor of perioperative morbidity than age, and therefore age alone should not determine whether gynecologists operate (Clin. Podiatr. Med. Surg. 2003;20:607-26). In elderly patients, we should consider preoperative consultation with the patient’s primary care physician, subspecialists, geriatricians, physical and occupational therapists, and anesthesiologist to evaluate comorbidities and optimize preoperative status. Posthospitalization discharge planning also should start preoperatively if there is a concern that a patient may not be able to be discharged home.

Gynecologists also should consider the indications for surgery and a patient’s life expectancy. Prior to surgery, surgeons should believe that each patient has an expected life span such that they will benefit from the surgery. We should perform the most appropriate and least aggressive surgery and take into consideration the duration of the procedure. Surgeons also should consider functional outcomes, including quality of life, and the goal should be a postoperative return to normal function (Mt. Sinai J. Med. 2012;79:95-106).

Other factors to consider once a gynecologist has decided to operate on an elderly patient include surgical approach, mode of anesthesia, and the need for operative staging. An abdominal surgery is a risk factor for perioperative morbidity. Therefore, a laparoscopic or vaginal approach should be considered in elderly patients. These surgeries may promote more rapid return to functional status, thereby decreasing the risk of postoperative respiratory complications, length of hospital stay, and risk of delirium and postoperative cognitive decline (Curr. Opin. Obstet. Gynecol. 1997;9:300-305).Unfortunately, changes in cardiovascular physiology during abdominal insufflation and desufflation may lead to decreased peripheral perfusion and increased cardiac output. Additionally, a laparoscopic approach can lead to increases in operating time. Therefore, a gynecologist must carefully consider surgical approach.

Another important aspect to consider prior to surgery is whether the procedure can be performed under neuraxial anesthesia. An epidural could be left in place for postoperative pain control and eliminate the need for general anesthesia and postoperative pain control with narcotics. Gynecologic oncologists specifically must consider whether extending the procedure to include surgical staging is necessary and appropriate for each individual patient. A specific example concerns lymph node dissection in endometrial cancer. A recent study has shown that 5-year survival does not differ in women older than 80 years with low-grade endometrial cancer if lymph node dissection is omitted (Gynecol. Oncol. 2012;126:12-15).This may be important in limiting total anesthetic time to under 3 hours in an attempt to decrease perioperative morbidity and mortality.

Specific operating room considerations include patient position, coverage, and orientation. Elderly patients have fragile skin with decreased elasticity and decreased muscle mass. Therefore, they are more sensitive than their younger counterparts to bruising, skin tears, pressure ulcers, and hypothermia. Extra care must be taken during patient positioning to pad joints, avoid tape on fragile skin, and keep her covered with blankets or a warming device. Elderly patients also are at increased risk for venous thromboembolism; therefore sequential compression devices and, potentially, chemoprophylaxis should be used intraoperatively. On emergence from anesthesia, elderly patients should be given their glasses, and operating room staff should speak clearly and loudly to orient the patient to their situation.

Postoperatively, providers and family should continue to orient and reorient elderly patients to person, place, and situation. Good pain control is important, especially with larger abdominal incisions, to decrease respiratory complications and promote early ambulation. NSAIDs or neuraxial anesthesia should be considered to decrease the use of potentially sedating opioids. But avoid NSAIDs in patients with dehydration, congestive heart failure, and preexisting renal disease. It also is important to get patients back to their activities of daily living as soon as possible; therefore inpatient physical and occupational therapy should be considered on the day following surgery. Prior to discharge, care to avoid too many additional medications and attention to potential medication interactions are critical.

Elderly women are at risk for increased postoperative morbidity and mortality; however, with appropriate perioperative planning, these risks can be minimized. Each patient and her situation should be carefully evaluated, and a multidisciplinary team assembled to assist with taking the steps necessary to promote a smooth transition to the outpatient setting and decrease complications.

Dr. Hacker is a rising fourth-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. E-mail them at obnews@frontlinemedcom.com.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.

Men and women older than 65 years make up the fastest-growing portion of the U.S. population. By 2020, more than 16% of the American population is projected to be older than 65 years of age, according to projections by the U.S. Census.

As the population ages, an increasing proportion of our patients will be considered elderly (greater than 65 years), and up to 50% of surgeries will be performed in these patients. Perioperative mortality has decreased over the past 50 years in all patients, but elderly patients continue to have higher perioperative morbidity and mortality than their younger counterparts (Mt. Sinai J. Med. 2012;79:95-106). This increased morbidity is particularly relevant to gynecologists as 60% of the population older than 65 years is female. It is also important to note that 30-day mortality is higher in patients older than 80 years.

Significant risk factors in any surgical population include underlying cardiac and pulmonary disease, smoking, obesity, prior or current abdominal/thoracic surgery, and type of anesthesia (Prim. Care 1989;16:361-76).

Studies conflict on whether age alone is an independent risk factor for perioperative morbidity and mortality. Older patients tend to have more underlying diseases, thus placing them at increased risk for perioperative morbidity. Unfortunately, the presence of coexisting comorbidities does not alone account for poor outcomes. In one large population-based study, even healthy elderly patients continued to have higher morbidity and mortality. This is likely because elderly patients respond differently to perioperative physiologic stressors and pharmacologic interventions (Anesthesiology 2009;110:1176-81).

Organ function declines with age, but there is wide inter- and intraindividual variability in the rate of decline (Anesthesiology 2009;110:1176-81). Because of the potential for interpatient aging differences, gynecologists must assess each patient; chronologic age and biologic age can differ significantly (Semin. Perioper. Nurs. 1997;6:14-20). There are changes in pharmacokinetics and pharmacodynamics related to age and organ function changes. Alterations in kidney and liver function result in slower rates of drug metabolism, potentially increasing concentrations of medications in older patients. In addition to considering alterations in dosing, physicians must consider the possibility of increased or decreased sensitivities to medications resulting from alterations in pharmacodynamics.

Patients over 80 years old have increased perioperative morbidity and mortality. Respiratory and urinary tract complications are the most common, but cardiac complications are more severe in these patients (Mt. Sinai J. Med. 2012;79:95-106). Respiratory complications account for 40% of surgical complications and up to 20% of all surgery-related deaths. Respiratory morbidity is increased in patients who are under anesthesia for more than 3 hours or have abdominal and/or thoracic incisions (Can. Oper. Room Nurs. J. 2007;25:34-5, 37-41). Although less prevalent, cardiovascular complications can be devastating short term, accounting for 50% of postoperative mortality in the elderly. Complications increase with age, and 20% of patients older than 80 years experience at least one complication, which is particularly concerning given that the presence of one complication increases mortality sixfold.

In addition to being at greater risk for physical complications, elderly patients are at increased risk of experiencing psychological and neurologic complications in the postoperative period. Up to 15% of elderly patients can develop postoperative delirium, which is associated with longer hospital stays and other long-term consequences (Prim. Care 1989;16:361-76). Postoperative cognitive decline is a research finding of deterioration in neurocognitive testing that is also seen in elderly patients. Practically, this decline is manifested by a decreased ability to perform activities of daily living and instrumental activities of daily living. This decline may resolve over the first year postoperatively, and the incidence ranges from 5% to 15%. Patients older than 70 years are more likely to experience postoperative delirium and cognitive decline (Curr. Opin. Anaesthesiol. 2010;23:201-8).

As the population ages, gynecologists are going to face an increase in the number of women requiring surgical intervention for both benign and malignant indications. A thorough knowledge of the risks associated with this population is of the utmost importance so that we can appropriately counsel our patients and their families and take steps to minimize complications.

Dr. Hacker is a rising fourth-year resident in the department obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Hacker and Dr. Gehrig said they had no relevant financial disclosures.