Dario R. Roque, MD

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.

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.

An adnexal mass is a common gynecological presentation that can affect women of all ages. Typically, the mass is identified during an annual pelvic exam or incidentally when patients undergo pelvic imaging for evaluation of gastrointestinal or gynecological complaints.

The main goal of evaluating an adnexal mass in the nonacute setting is to rule out malignancy. A careful evaluation is needed to accurately distinguish benign from malignant masses, but often a definitive diagnosis only can be achieved with surgery. Hence, in the United States, women have a 5%-10% chance of undergoing surgery to evaluate a mass, but only 13%-21% of these patients are diagnosed with an ovarian cancer (Obstet. Gynecol. 2007;110:201-14).

We will review a stepwise approach for the evaluation of a newly diagnosed mass. As part of our review, we will discuss imaging findings that should prompt surgical evaluation or continued observation, as well as the correct use of the currently available serum biomarkers.

The majority of adnexal masses are benign and present most commonly in premenopausal women. However, in the outpatient setting, the evaluation approach should be aimed at ruling out malignancy regardless of age or reproductive status. The patient’s age should be considered clinically, as the suspicion for ovarian cancer should be heightened in postmenopausal women.

The evaluation should start with a detailed history because it may help in determining the etiology of the mass. Pelvic pain and pressure are very common but nonspecific symptoms in women with adnexal masses. However, if the pain is of sudden onset, urgent evaluation is warranted to rule out adnexal torsion or a ruptured hemorrhagic cyst. A history of dysmenorrhea and/or dyspareunia may suggest endometriosis and coexisting endometrioma, whereas a patient with fever and a vaginal discharge should be evaluated for a tubo-ovarian abscess.

Patients also should be asked about symptoms associated with ovarian cancer including early satiety, constipation, and bloating, as well as their duration. In addition, abnormal uterine bleeding or virilization may suggest the presence of estrogen- or testosterone-secreting tumors. Lastly, a detailed family history is important, as the presence of ovarian, breast, or colon cancer in the family would increase suspicion for hereditary ovarian cancer syndromes.

A thorough physical exam should include a speculum exam as well as bimanual and rectovaginal exams. The focus of the pelvic exam should be determining the size, mobility, and consistency of the mass, as well as other findings that may help discriminate benign versus malignant neoplasms. Malignant masses are usually solid, irregular in shape, and tend to be fixed. Nodularity in the posterior cul-de-sac also is associated with malignancy. The abdominal exam should focus on the presence or absence of ascites (fluid wave), an omental mass, or inguinal adenopathy. However, none of the findings on exam are specific for an ovarian or fallopian tube malignancy, and imaging should be obtained for further evaluation.

Ultrasound is the imaging study of choice for the evaluation of an adnexal mass because it is less expensive than and diagnostically equivalent to other imaging modalities. A pelvic ultrasound can help delineate the anatomic origin of the mass, but it also can detect characteristics of the mass that may help with the diagnosis, and the decision of whether or not to proceed to surgery. Endometriomas, mature teratomas (dermoid cysts), simple ovarian cysts, and hemorrhagic cysts have sonographic features that are highly predictive of the histology. Depending on whether or not the patient is symptomatic, the patient’s age, and comorbidities, these masses might be followed expectantly.

Ultrasound features that are suggestive of malignancy include solid components, septations greater than 2-3 mm, and vascular flow. The presence of ascites or peritoneal nodules detected at the time of ultrasound also is highly suspicious of malignancy in patients with a pelvic mass. If a pelvic ultrasound is equivocal, pelvic magnetic resonance imaging (MRI) is the second study of choice. Computed tomography (CT scan) should be used to evaluate for metastatic disease in patients with suspected ovarian carcinoma (ascites, adenopathy, peritoneal thickening or nodularity, omental thickening).

Serum biomarkers also may aid in the evaluation. The most well-studied and commonly used biomarker in the evaluation of an adnexal mass is CA-125. In general, the utility of CA-125 is limited mainly because of its low specificity, especially in premenopausal women. However, it can be used as adjunct when an ovarian malignancy is suspected based on the patient’s history, risk factors, and imaging findings. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) advise referral to a gynecologic oncologist for postmenopausal women with an elevated CA-125. Meanwhile, for premenopausal women, the recommendation is for referral of those with a "very elevated" CA-125. However, a specific value has not been established (Obstet. Gynecol. 2011;117:742-6).

CA-125 by itself should not be used to decide whether or not to take a patient to surgery. Nevertheless, once the decision to operate has been made, CA-125 can be used in conjunction with HE4 to calculate a Risk of Malignancy Algorithm (ROMA) score. The score is based on menopausal status, and if the calculated risk is elevated, patient referral to a gynecologic oncologist for her surgery should be strongly considered.

Similarly, the OVA1 test is currently approved by the Food and Drug Administration to assess the likelihood of malignancy in patients who are having surgery for an adnexal mass. The test is also based on menopausal status, and if elevated, a referral to a gynecologic oncologist is recommended. In young women with adnexal masses, germ cell tumor markers may be more helpful (lactate dehydrogenase [LDH], human chorionic gonadotropin [hCG], alpha-fetoprotein [AFP]), while in patients with signs or symptoms of estrogen or androgen excess, sex cord-stromal tumor markers (inhibin B, anti-Müllerian hormone [AMH], testosterone, dehydroepiandrosterone [DHEA], estradiol) would be appropriate to obtain. While no tumor marker is "diagnostic," the results may assist in the decision to perform surgery and consider referral to a gynecologic oncologist.

In summary, the workup for an adnexal mass should include a detailed medical and family history, a thorough physical exam, and imaging with pelvic ultrasound. For premenopausal women, there is a higher incidence of adnexal masses, and, in fact, most of them are benign. In these women, one must weigh the risk/benefit of close monitoring with pelvic ultrasound versus surgical intervention. A serum CA-125 can be helpful, but only if it is significantly elevated.

If uncertainty remains after a complete evaluation has been performed, it is appropriate to refer to a gynecologic oncologist. In postmenopausal women, serum biomarkers should be used in conjunction with the history, physical, and ultrasound because of the higher risk of malignancy. In addition, surgical intervention should be offered to these patients regardless of serum marker values in the setting of a complex mass. If there is high suspicion for malignancy by history and imaging or elevated ROMA or OVA1, referral to a gynecologic oncologist is prudent.

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 of North Carolina, Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina. Neither Dr. Clarke-Pearson nor Dr. Roque has any relevant financial disclosures. E-mail them at obnews@frontlinemedcom.com.

An adnexal mass is a common gynecological presentation that can affect women of all ages. Typically, the mass is identified during an annual pelvic exam or incidentally when patients undergo pelvic imaging for evaluation of gastrointestinal or gynecological complaints.

The main goal of evaluating an adnexal mass in the nonacute setting is to rule out malignancy. A careful evaluation is needed to accurately distinguish benign from malignant masses, but often a definitive diagnosis only can be achieved with surgery. Hence, in the United States, women have a 5%-10% chance of undergoing surgery to evaluate a mass, but only 13%-21% of these patients are diagnosed with an ovarian cancer (Obstet. Gynecol. 2007;110:201-14).

We will review a stepwise approach for the evaluation of a newly diagnosed mass. As part of our review, we will discuss imaging findings that should prompt surgical evaluation or continued observation, as well as the correct use of the currently available serum biomarkers.

The majority of adnexal masses are benign and present most commonly in premenopausal women. However, in the outpatient setting, the evaluation approach should be aimed at ruling out malignancy regardless of age or reproductive status. The patient’s age should be considered clinically, as the suspicion for ovarian cancer should be heightened in postmenopausal women.

The evaluation should start with a detailed history because it may help in determining the etiology of the mass. Pelvic pain and pressure are very common but nonspecific symptoms in women with adnexal masses. However, if the pain is of sudden onset, urgent evaluation is warranted to rule out adnexal torsion or a ruptured hemorrhagic cyst. A history of dysmenorrhea and/or dyspareunia may suggest endometriosis and coexisting endometrioma, whereas a patient with fever and a vaginal discharge should be evaluated for a tubo-ovarian abscess.

Patients also should be asked about symptoms associated with ovarian cancer including early satiety, constipation, and bloating, as well as their duration. In addition, abnormal uterine bleeding or virilization may suggest the presence of estrogen- or testosterone-secreting tumors. Lastly, a detailed family history is important, as the presence of ovarian, breast, or colon cancer in the family would increase suspicion for hereditary ovarian cancer syndromes.

A thorough physical exam should include a speculum exam as well as bimanual and rectovaginal exams. The focus of the pelvic exam should be determining the size, mobility, and consistency of the mass, as well as other findings that may help discriminate benign versus malignant neoplasms. Malignant masses are usually solid, irregular in shape, and tend to be fixed. Nodularity in the posterior cul-de-sac also is associated with malignancy. The abdominal exam should focus on the presence or absence of ascites (fluid wave), an omental mass, or inguinal adenopathy. However, none of the findings on exam are specific for an ovarian or fallopian tube malignancy, and imaging should be obtained for further evaluation.

Ultrasound is the imaging study of choice for the evaluation of an adnexal mass because it is less expensive than and diagnostically equivalent to other imaging modalities. A pelvic ultrasound can help delineate the anatomic origin of the mass, but it also can detect characteristics of the mass that may help with the diagnosis, and the decision of whether or not to proceed to surgery. Endometriomas, mature teratomas (dermoid cysts), simple ovarian cysts, and hemorrhagic cysts have sonographic features that are highly predictive of the histology. Depending on whether or not the patient is symptomatic, the patient’s age, and comorbidities, these masses might be followed expectantly.

Ultrasound features that are suggestive of malignancy include solid components, septations greater than 2-3 mm, and vascular flow. The presence of ascites or peritoneal nodules detected at the time of ultrasound also is highly suspicious of malignancy in patients with a pelvic mass. If a pelvic ultrasound is equivocal, pelvic magnetic resonance imaging (MRI) is the second study of choice. Computed tomography (CT scan) should be used to evaluate for metastatic disease in patients with suspected ovarian carcinoma (ascites, adenopathy, peritoneal thickening or nodularity, omental thickening).

Serum biomarkers also may aid in the evaluation. The most well-studied and commonly used biomarker in the evaluation of an adnexal mass is CA-125. In general, the utility of CA-125 is limited mainly because of its low specificity, especially in premenopausal women. However, it can be used as adjunct when an ovarian malignancy is suspected based on the patient’s history, risk factors, and imaging findings. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) advise referral to a gynecologic oncologist for postmenopausal women with an elevated CA-125. Meanwhile, for premenopausal women, the recommendation is for referral of those with a "very elevated" CA-125. However, a specific value has not been established (Obstet. Gynecol. 2011;117:742-6).

CA-125 by itself should not be used to decide whether or not to take a patient to surgery. Nevertheless, once the decision to operate has been made, CA-125 can be used in conjunction with HE4 to calculate a Risk of Malignancy Algorithm (ROMA) score. The score is based on menopausal status, and if the calculated risk is elevated, patient referral to a gynecologic oncologist for her surgery should be strongly considered.

Similarly, the OVA1 test is currently approved by the Food and Drug Administration to assess the likelihood of malignancy in patients who are having surgery for an adnexal mass. The test is also based on menopausal status, and if elevated, a referral to a gynecologic oncologist is recommended. In young women with adnexal masses, germ cell tumor markers may be more helpful (lactate dehydrogenase [LDH], human chorionic gonadotropin [hCG], alpha-fetoprotein [AFP]), while in patients with signs or symptoms of estrogen or androgen excess, sex cord-stromal tumor markers (inhibin B, anti-Müllerian hormone [AMH], testosterone, dehydroepiandrosterone [DHEA], estradiol) would be appropriate to obtain. While no tumor marker is "diagnostic," the results may assist in the decision to perform surgery and consider referral to a gynecologic oncologist.

In summary, the workup for an adnexal mass should include a detailed medical and family history, a thorough physical exam, and imaging with pelvic ultrasound. For premenopausal women, there is a higher incidence of adnexal masses, and, in fact, most of them are benign. In these women, one must weigh the risk/benefit of close monitoring with pelvic ultrasound versus surgical intervention. A serum CA-125 can be helpful, but only if it is significantly elevated.

If uncertainty remains after a complete evaluation has been performed, it is appropriate to refer to a gynecologic oncologist. In postmenopausal women, serum biomarkers should be used in conjunction with the history, physical, and ultrasound because of the higher risk of malignancy. In addition, surgical intervention should be offered to these patients regardless of serum marker values in the setting of a complex mass. If there is high suspicion for malignancy by history and imaging or elevated ROMA or OVA1, referral to a gynecologic oncologist is prudent.

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 of North Carolina, Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina. Neither Dr. Clarke-Pearson nor Dr. Roque has any relevant financial disclosures. E-mail them at obnews@frontlinemedcom.com.

An adnexal mass is a common gynecological presentation that can affect women of all ages. Typically, the mass is identified during an annual pelvic exam or incidentally when patients undergo pelvic imaging for evaluation of gastrointestinal or gynecological complaints.

The main goal of evaluating an adnexal mass in the nonacute setting is to rule out malignancy. A careful evaluation is needed to accurately distinguish benign from malignant masses, but often a definitive diagnosis only can be achieved with surgery. Hence, in the United States, women have a 5%-10% chance of undergoing surgery to evaluate a mass, but only 13%-21% of these patients are diagnosed with an ovarian cancer (Obstet. Gynecol. 2007;110:201-14).

We will review a stepwise approach for the evaluation of a newly diagnosed mass. As part of our review, we will discuss imaging findings that should prompt surgical evaluation or continued observation, as well as the correct use of the currently available serum biomarkers.

The majority of adnexal masses are benign and present most commonly in premenopausal women. However, in the outpatient setting, the evaluation approach should be aimed at ruling out malignancy regardless of age or reproductive status. The patient’s age should be considered clinically, as the suspicion for ovarian cancer should be heightened in postmenopausal women.

The evaluation should start with a detailed history because it may help in determining the etiology of the mass. Pelvic pain and pressure are very common but nonspecific symptoms in women with adnexal masses. However, if the pain is of sudden onset, urgent evaluation is warranted to rule out adnexal torsion or a ruptured hemorrhagic cyst. A history of dysmenorrhea and/or dyspareunia may suggest endometriosis and coexisting endometrioma, whereas a patient with fever and a vaginal discharge should be evaluated for a tubo-ovarian abscess.

Patients also should be asked about symptoms associated with ovarian cancer including early satiety, constipation, and bloating, as well as their duration. In addition, abnormal uterine bleeding or virilization may suggest the presence of estrogen- or testosterone-secreting tumors. Lastly, a detailed family history is important, as the presence of ovarian, breast, or colon cancer in the family would increase suspicion for hereditary ovarian cancer syndromes.

A thorough physical exam should include a speculum exam as well as bimanual and rectovaginal exams. The focus of the pelvic exam should be determining the size, mobility, and consistency of the mass, as well as other findings that may help discriminate benign versus malignant neoplasms. Malignant masses are usually solid, irregular in shape, and tend to be fixed. Nodularity in the posterior cul-de-sac also is associated with malignancy. The abdominal exam should focus on the presence or absence of ascites (fluid wave), an omental mass, or inguinal adenopathy. However, none of the findings on exam are specific for an ovarian or fallopian tube malignancy, and imaging should be obtained for further evaluation.

Ultrasound is the imaging study of choice for the evaluation of an adnexal mass because it is less expensive than and diagnostically equivalent to other imaging modalities. A pelvic ultrasound can help delineate the anatomic origin of the mass, but it also can detect characteristics of the mass that may help with the diagnosis, and the decision of whether or not to proceed to surgery. Endometriomas, mature teratomas (dermoid cysts), simple ovarian cysts, and hemorrhagic cysts have sonographic features that are highly predictive of the histology. Depending on whether or not the patient is symptomatic, the patient’s age, and comorbidities, these masses might be followed expectantly.

Ultrasound features that are suggestive of malignancy include solid components, septations greater than 2-3 mm, and vascular flow. The presence of ascites or peritoneal nodules detected at the time of ultrasound also is highly suspicious of malignancy in patients with a pelvic mass. If a pelvic ultrasound is equivocal, pelvic magnetic resonance imaging (MRI) is the second study of choice. Computed tomography (CT scan) should be used to evaluate for metastatic disease in patients with suspected ovarian carcinoma (ascites, adenopathy, peritoneal thickening or nodularity, omental thickening).

Serum biomarkers also may aid in the evaluation. The most well-studied and commonly used biomarker in the evaluation of an adnexal mass is CA-125. In general, the utility of CA-125 is limited mainly because of its low specificity, especially in premenopausal women. However, it can be used as adjunct when an ovarian malignancy is suspected based on the patient’s history, risk factors, and imaging findings. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Oncologists (SGO) advise referral to a gynecologic oncologist for postmenopausal women with an elevated CA-125. Meanwhile, for premenopausal women, the recommendation is for referral of those with a "very elevated" CA-125. However, a specific value has not been established (Obstet. Gynecol. 2011;117:742-6).

CA-125 by itself should not be used to decide whether or not to take a patient to surgery. Nevertheless, once the decision to operate has been made, CA-125 can be used in conjunction with HE4 to calculate a Risk of Malignancy Algorithm (ROMA) score. The score is based on menopausal status, and if the calculated risk is elevated, patient referral to a gynecologic oncologist for her surgery should be strongly considered.

Similarly, the OVA1 test is currently approved by the Food and Drug Administration to assess the likelihood of malignancy in patients who are having surgery for an adnexal mass. The test is also based on menopausal status, and if elevated, a referral to a gynecologic oncologist is recommended. In young women with adnexal masses, germ cell tumor markers may be more helpful (lactate dehydrogenase [LDH], human chorionic gonadotropin [hCG], alpha-fetoprotein [AFP]), while in patients with signs or symptoms of estrogen or androgen excess, sex cord-stromal tumor markers (inhibin B, anti-Müllerian hormone [AMH], testosterone, dehydroepiandrosterone [DHEA], estradiol) would be appropriate to obtain. While no tumor marker is "diagnostic," the results may assist in the decision to perform surgery and consider referral to a gynecologic oncologist.

In summary, the workup for an adnexal mass should include a detailed medical and family history, a thorough physical exam, and imaging with pelvic ultrasound. For premenopausal women, there is a higher incidence of adnexal masses, and, in fact, most of them are benign. In these women, one must weigh the risk/benefit of close monitoring with pelvic ultrasound versus surgical intervention. A serum CA-125 can be helpful, but only if it is significantly elevated.

If uncertainty remains after a complete evaluation has been performed, it is appropriate to refer to a gynecologic oncologist. In postmenopausal women, serum biomarkers should be used in conjunction with the history, physical, and ultrasound because of the higher risk of malignancy. In addition, surgical intervention should be offered to these patients regardless of serum marker values in the setting of a complex mass. If there is high suspicion for malignancy by history and imaging or elevated ROMA or OVA1, referral to a gynecologic oncologist is prudent.

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 of North Carolina, Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina. Neither Dr. Clarke-Pearson nor Dr. Roque has any relevant financial disclosures. E-mail them at obnews@frontlinemedcom.com.