Daniel L. Clarke-Pearson, MD

Vaginal cuff dehiscence, or separation of the vaginal incision, is a rare postoperative complication unique to hysterectomy. Morbidity related to evisceration of abdominal contents can be profound and prompt intervention is required.

A 10-year observational study of 11,000 patients described a 0.24% cumulative incidence after all modes of hysterectomy.¹ Though data are varied, the mode of hysterectomy does have an impact on the risk of dehiscence.

Laparoscopic (0.64%-1.35%) and robotic (0.46%-1.5%) hysterectomy have a higher incidence than abdominal (0.15%-0.26%) and vaginal (0.08%-0.25%) approaches.² The use of monopolar cautery for colpotomy and different closure techniques may account for these differences.

Cuff cellulitis, early sexual intercourse, cigarette smoking, poor nutrition, obesity, menopausal status, and corticosteroid use are all proposed risk factors that promote infection, pressure at the vaginal cuff, and poor wound healing. Although some are modifiable, the rarity of this complication has made establishing causality and promoting prevention challenging.

Prevention

• Preoperatively. Treating bacterial vaginosis, Trichomonas vaginalis, gonorrhea, and chlamydia can decrease the risk of cuff cellulitis and dehiscence.³

• Intraoperatively. Surgeons should ensure adequate vaginal margins (greater than 1 cm) with full-thickness cuff closures while avoiding excessive electrocautery.⁴ Retrospective data show that transvaginal cuff closure is associated with a decreased risk of dehiscence.⁵ However, given the lack of randomized data and the difficulty controlling for surgeon experience, gynecologists should use the approach that they are most comfortable with. Though the various laparoscopic cuff closure techniques have limited evidence regarding superiority, some experts propose using two-layer cuff closure and barbed sutures.^6-8 Several retrospective studies have found an equivalent or a decreased incidence of cuff dehiscence with barbed sutures, compared with other methods (e.g., 0-Vicryl, Endo Stitch).^9,10

• Postoperatively. Women should avoid intercourse and lifting more than 15 pounds for at least 6-8 weeks as the vaginal cuff gains tensile strength. Vaginal estrogen can promote healing in postmenopausal patients.¹¹

Management

Patients with vaginal cuff dehiscence commonly present within the first several weeks to months after surgery with pelvic pain (60%-100%), vaginal bleeding (30%-60%), vaginal discharge (30%), or vaginal pressure/mass (30%).^1,7 Posthysterectomy patients with these complaints warrant an urgent evaluation. The diagnosis is made during a pelvic exam.

Broad-spectrum antibiotics are necessary because all vaginal cuff separations or dehiscences expose the peritoneal cavity to vaginal flora. Nonsurgical management is reasonable for small separations – less than 25% of the cuff – if there is no evidence of evisceration.

However, surgically closing all recognized cuff dehiscences is reasonable, given the potential for further separation. A vaginal approach is preferred when possible. Women with vaginal cuff dehiscence, stable vital signs, and no evidence of bowel evisceration can be repaired vaginally without an abdominal survey.

In contrast, women with bowel evisceration have a surgical emergency because of the risk of peritonitis and bowel injury. If the eviscerated bowel is not reducible, it should be irrigated and wrapped in a warm moist towel or gauze in preparation for inspection and reduction in the operating room. If the bowel is reducible, the patient can be placed in Trendelenburg’s position. Her vagina should be packed to reduce the risk of re-evisceration as she moves toward operative cuff repair.

If the physician is concerned about bowel injury, inspection via laparoscopy or laparotomy would be reasonable. However, when bowel injury is not suspected, a vaginal technique for dehiscence repair has been described by Matthews et al.:¹²

1. Expose the cuff with a weighted speculum and Breisky-Navratil retractors.

2. Sharply debride the cuff edges back to viable tissue.

3. Dissect adherent bowel or omentum to allow for full-thickness closure.

4. Place full-thickness, interrupted delayed absorbable sutures to reapproximate the cuff edges.

Cuff dehiscence is a rare but potentially morbid complication of hysterectomy. Prevention, recognition, and appropriate management can avoid life-threatening sequelae.

References

1. Obstet Gynecol. 2011 Oct;118(4):794-801.

2. JSLS. 2012 Oct-Dec;16(4):530-6.

3. Am J Obstet Gynecol. 1990 Sep;163(3):1016-21; discussion 1021-3.

4. Obstet Gynecol. 2013 Mar;121(3):654-73.

5. Obstet Gynecol. 2012 Sep;120(3):516-23.

6. J Am Assoc Gynecol Laparosc. 2002 Nov;9(4):474-80.

7. Eur J Obstet Gynecol Reprod Biol. 2006 Mar 1;125(1):134-8.

8. Obstet Gynecol. 2009 Aug;114(2 Pt 1):231-5.

9. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):218-23.

10. Int J Surg. 2015 Jul;19:27-30.

11. Maturitas. 2006 Feb 20;53(3):282-98.

12. Obstet Gynecol. 2014 Oct;124(4):705-8.

Dr. Pierce is a gynecologic oncology fellow 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 professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

Vaginal cuff dehiscence, or separation of the vaginal incision, is a rare postoperative complication unique to hysterectomy. Morbidity related to evisceration of abdominal contents can be profound and prompt intervention is required.

A 10-year observational study of 11,000 patients described a 0.24% cumulative incidence after all modes of hysterectomy.¹ Though data are varied, the mode of hysterectomy does have an impact on the risk of dehiscence.

Laparoscopic (0.64%-1.35%) and robotic (0.46%-1.5%) hysterectomy have a higher incidence than abdominal (0.15%-0.26%) and vaginal (0.08%-0.25%) approaches.² The use of monopolar cautery for colpotomy and different closure techniques may account for these differences.

Cuff cellulitis, early sexual intercourse, cigarette smoking, poor nutrition, obesity, menopausal status, and corticosteroid use are all proposed risk factors that promote infection, pressure at the vaginal cuff, and poor wound healing. Although some are modifiable, the rarity of this complication has made establishing causality and promoting prevention challenging.

Prevention

• Preoperatively. Treating bacterial vaginosis, Trichomonas vaginalis, gonorrhea, and chlamydia can decrease the risk of cuff cellulitis and dehiscence.³

• Intraoperatively. Surgeons should ensure adequate vaginal margins (greater than 1 cm) with full-thickness cuff closures while avoiding excessive electrocautery.⁴ Retrospective data show that transvaginal cuff closure is associated with a decreased risk of dehiscence.⁵ However, given the lack of randomized data and the difficulty controlling for surgeon experience, gynecologists should use the approach that they are most comfortable with. Though the various laparoscopic cuff closure techniques have limited evidence regarding superiority, some experts propose using two-layer cuff closure and barbed sutures.^6-8 Several retrospective studies have found an equivalent or a decreased incidence of cuff dehiscence with barbed sutures, compared with other methods (e.g., 0-Vicryl, Endo Stitch).^9,10

• Postoperatively. Women should avoid intercourse and lifting more than 15 pounds for at least 6-8 weeks as the vaginal cuff gains tensile strength. Vaginal estrogen can promote healing in postmenopausal patients.¹¹

Management

Patients with vaginal cuff dehiscence commonly present within the first several weeks to months after surgery with pelvic pain (60%-100%), vaginal bleeding (30%-60%), vaginal discharge (30%), or vaginal pressure/mass (30%).^1,7 Posthysterectomy patients with these complaints warrant an urgent evaluation. The diagnosis is made during a pelvic exam.

Broad-spectrum antibiotics are necessary because all vaginal cuff separations or dehiscences expose the peritoneal cavity to vaginal flora. Nonsurgical management is reasonable for small separations – less than 25% of the cuff – if there is no evidence of evisceration.

However, surgically closing all recognized cuff dehiscences is reasonable, given the potential for further separation. A vaginal approach is preferred when possible. Women with vaginal cuff dehiscence, stable vital signs, and no evidence of bowel evisceration can be repaired vaginally without an abdominal survey.

In contrast, women with bowel evisceration have a surgical emergency because of the risk of peritonitis and bowel injury. If the eviscerated bowel is not reducible, it should be irrigated and wrapped in a warm moist towel or gauze in preparation for inspection and reduction in the operating room. If the bowel is reducible, the patient can be placed in Trendelenburg’s position. Her vagina should be packed to reduce the risk of re-evisceration as she moves toward operative cuff repair.

If the physician is concerned about bowel injury, inspection via laparoscopy or laparotomy would be reasonable. However, when bowel injury is not suspected, a vaginal technique for dehiscence repair has been described by Matthews et al.:¹²

1. Expose the cuff with a weighted speculum and Breisky-Navratil retractors.

2. Sharply debride the cuff edges back to viable tissue.

3. Dissect adherent bowel or omentum to allow for full-thickness closure.

4. Place full-thickness, interrupted delayed absorbable sutures to reapproximate the cuff edges.

Cuff dehiscence is a rare but potentially morbid complication of hysterectomy. Prevention, recognition, and appropriate management can avoid life-threatening sequelae.

References

1. Obstet Gynecol. 2011 Oct;118(4):794-801.

2. JSLS. 2012 Oct-Dec;16(4):530-6.

3. Am J Obstet Gynecol. 1990 Sep;163(3):1016-21; discussion 1021-3.

4. Obstet Gynecol. 2013 Mar;121(3):654-73.

5. Obstet Gynecol. 2012 Sep;120(3):516-23.

6. J Am Assoc Gynecol Laparosc. 2002 Nov;9(4):474-80.

7. Eur J Obstet Gynecol Reprod Biol. 2006 Mar 1;125(1):134-8.

8. Obstet Gynecol. 2009 Aug;114(2 Pt 1):231-5.

9. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):218-23.

10. Int J Surg. 2015 Jul;19:27-30.

11. Maturitas. 2006 Feb 20;53(3):282-98.

12. Obstet Gynecol. 2014 Oct;124(4):705-8.

Dr. Pierce is a gynecologic oncology fellow 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 professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

Vaginal cuff dehiscence, or separation of the vaginal incision, is a rare postoperative complication unique to hysterectomy. Morbidity related to evisceration of abdominal contents can be profound and prompt intervention is required.

A 10-year observational study of 11,000 patients described a 0.24% cumulative incidence after all modes of hysterectomy.¹ Though data are varied, the mode of hysterectomy does have an impact on the risk of dehiscence.

Laparoscopic (0.64%-1.35%) and robotic (0.46%-1.5%) hysterectomy have a higher incidence than abdominal (0.15%-0.26%) and vaginal (0.08%-0.25%) approaches.² The use of monopolar cautery for colpotomy and different closure techniques may account for these differences.

Cuff cellulitis, early sexual intercourse, cigarette smoking, poor nutrition, obesity, menopausal status, and corticosteroid use are all proposed risk factors that promote infection, pressure at the vaginal cuff, and poor wound healing. Although some are modifiable, the rarity of this complication has made establishing causality and promoting prevention challenging.

Prevention

• Preoperatively. Treating bacterial vaginosis, Trichomonas vaginalis, gonorrhea, and chlamydia can decrease the risk of cuff cellulitis and dehiscence.³

• Intraoperatively. Surgeons should ensure adequate vaginal margins (greater than 1 cm) with full-thickness cuff closures while avoiding excessive electrocautery.⁴ Retrospective data show that transvaginal cuff closure is associated with a decreased risk of dehiscence.⁵ However, given the lack of randomized data and the difficulty controlling for surgeon experience, gynecologists should use the approach that they are most comfortable with. Though the various laparoscopic cuff closure techniques have limited evidence regarding superiority, some experts propose using two-layer cuff closure and barbed sutures.^6-8 Several retrospective studies have found an equivalent or a decreased incidence of cuff dehiscence with barbed sutures, compared with other methods (e.g., 0-Vicryl, Endo Stitch).^9,10

• Postoperatively. Women should avoid intercourse and lifting more than 15 pounds for at least 6-8 weeks as the vaginal cuff gains tensile strength. Vaginal estrogen can promote healing in postmenopausal patients.¹¹

Management

Patients with vaginal cuff dehiscence commonly present within the first several weeks to months after surgery with pelvic pain (60%-100%), vaginal bleeding (30%-60%), vaginal discharge (30%), or vaginal pressure/mass (30%).^1,7 Posthysterectomy patients with these complaints warrant an urgent evaluation. The diagnosis is made during a pelvic exam.

Broad-spectrum antibiotics are necessary because all vaginal cuff separations or dehiscences expose the peritoneal cavity to vaginal flora. Nonsurgical management is reasonable for small separations – less than 25% of the cuff – if there is no evidence of evisceration.

However, surgically closing all recognized cuff dehiscences is reasonable, given the potential for further separation. A vaginal approach is preferred when possible. Women with vaginal cuff dehiscence, stable vital signs, and no evidence of bowel evisceration can be repaired vaginally without an abdominal survey.

In contrast, women with bowel evisceration have a surgical emergency because of the risk of peritonitis and bowel injury. If the eviscerated bowel is not reducible, it should be irrigated and wrapped in a warm moist towel or gauze in preparation for inspection and reduction in the operating room. If the bowel is reducible, the patient can be placed in Trendelenburg’s position. Her vagina should be packed to reduce the risk of re-evisceration as she moves toward operative cuff repair.

If the physician is concerned about bowel injury, inspection via laparoscopy or laparotomy would be reasonable. However, when bowel injury is not suspected, a vaginal technique for dehiscence repair has been described by Matthews et al.:¹²

1. Expose the cuff with a weighted speculum and Breisky-Navratil retractors.

2. Sharply debride the cuff edges back to viable tissue.

3. Dissect adherent bowel or omentum to allow for full-thickness closure.

4. Place full-thickness, interrupted delayed absorbable sutures to reapproximate the cuff edges.

Cuff dehiscence is a rare but potentially morbid complication of hysterectomy. Prevention, recognition, and appropriate management can avoid life-threatening sequelae.

References

1. Obstet Gynecol. 2011 Oct;118(4):794-801.

2. JSLS. 2012 Oct-Dec;16(4):530-6.

3. Am J Obstet Gynecol. 1990 Sep;163(3):1016-21; discussion 1021-3.

4. Obstet Gynecol. 2013 Mar;121(3):654-73.

5. Obstet Gynecol. 2012 Sep;120(3):516-23.

6. J Am Assoc Gynecol Laparosc. 2002 Nov;9(4):474-80.

7. Eur J Obstet Gynecol Reprod Biol. 2006 Mar 1;125(1):134-8.

8. Obstet Gynecol. 2009 Aug;114(2 Pt 1):231-5.

9. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):218-23.

10. Int J Surg. 2015 Jul;19:27-30.

11. Maturitas. 2006 Feb 20;53(3):282-98.

12. Obstet Gynecol. 2014 Oct;124(4):705-8.

Dr. Pierce is a gynecologic oncology fellow 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 professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology 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 professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology 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 professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva frequently encountered by gynecologic providers. There has been an increase in the incidence of VIN in younger women in recent decades thought be to be secondary to human papillomavirus infection, cigarette smoking, and sexual behavior (J Reprod Med. 2000 Aug;45[8]:613-5).

Data from the Surveillance Epidemiology and End Results (SEER) database were significant for a 411% increase in the incidence of in situ carcinoma and a 20% increase in invasive vulvar carcinoma from 1973 to 2000 (Obstet Gynecol. 2006 May;107[5]:1018-22). In addition, younger age groups are seeing an increase of in situ disease until age 49. Vulvar cancer however, continues to be a disease of older age.

Terminology

Previously, the term vulvar intraepithelial neoplasia followed the cervical intraepithelial neoplasia (CIN) designation in the 1960s. Conventions for grading these lesions have changed over time. Most recently, in 2004, the International Society for the Study of Vulvar Disease (ISSVD), composed of dermatologists, pathologists, and gynecologists, agreed to change the classification of squamous VIN from the previous VIN 1-3 classification system. The committee described VIN in two forms, “usual type” and “differentiated type” (J Reprod Med 2005;50:807-10).

In making this transition, it was recognized that VIN 1 is not in fact an oncogenic lesion and is now solely referred to as condyloma acuminatum. Grade 2 and 3 are now collectively referred to as VIN. These changes made by the ISSVD reflect the current literature on grading of VIN. In addition to VIN 1 not having any progression to malignancy, it is a diagnosis that is difficult to reproduce and may, at times, reflect reactive changes or other dermatosis. VIN 2 and 3 are not discriminated from each other in a reproducible manner and clinically have no reason for individual distinction (J Low Genit Tract Dis. 2006 Jul;10[3]:161-9).

VIN, usual type is the most common intraepithelial lesion and is historically referred to as classic VIN or Bowen’s disease. This type is associated with HPV infection and includes the formerly described warty type, basaloid type, and mixed type. The carcinogenic subtypes of HPV, 16, 18, 31, and 33 are the most common HPV subtypes responsible. It should be noted, however, that diagnosis is morphological and not based on HPV testing. Usual type is also traditionally thought to be more closely associated with risk factors such as smoking and immunocompromised states.

VIN, differentiated type is not associated with the HPV virus and is frequently found in older women. This lesion is often associated with other dermatologic conditions such as lichen sclerosis and lichen simplex chronicus. Diagnosis is also made by histology with abnormal cells being confined to the parabasal and basal portion of the rete pegs. This type also finds genetic alterations that are seen in invasive squamous cell carcinoma (Appl Immunohistochem Mol Morphol 2001;9:150-63). Differentiated type is thought to be a precursor for HPV-negative keratinizing squamous cell carcinoma of the vulva (Am J Surg Pathol. 2000 Mar;24[3]:429-41).

As awareness of this distinct form of VIN increases and more is learned about the precursors of HPV-negative squamous cell carcinoma, physicians are encouraged to closely follow up hyperplastic lesions and lichen sclerosis with biopsies and excision. The diagnosis of differentiated VIN is rarely made at present; however, this distinction by the ISSVD may improve the ability of clinicians and pathologists to recognize this HPV-negative precursor before squamous cell carcinoma is present.

The Lower Anogenital Squamous Terminology project of the College of American Pathology and the American Society for Colposcopy and Cervical Pathology advocates for more consistent terminology across lower anogenital tract lesions. This terminology applies only to HPV-related lesions (usual type) and considers the VIN 1 or condyloma accuminatum to be a low-grade lesion (LSIL), and VIN 2-3 or usual type to be high-grade lesions (HSIL) (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

Many clinicians and pathologists have not adopted this most recent terminology; however, there is evidence that the ISSVD classification is the most clinically relevant.

Diagnosis

The majority of patients with any VIN will present with complaints of vulvar pruritus. However, women can also present with pain, burning, or dysuria, or can have an asymptomatic lesion found on pelvic exam. There are no recommended screening strategies to diagnose early VIN. Cytologic testing is complicated by the keratinization of the vulva, making this an unreliable diagnostic assessment.

On physical exam, VIN can have a heterogeneous presentation including papules, plaques, color variations, or ulcer. Differentiated type is thought to have a more defined appearance that frequently develops in the setting of other vulvar dermatosis. These are distinct, solitary lesions that are commonly raised, can have an overlying scale, and have ill-defined borders. A distinct lesion with ulceration or erosion is concerning for invasion.

Diagnosis is ultimately made by biopsy. Physicians should have a low threshold to biopsy any suspicious lesions or those unresponsive to therapy. Colposcopy is a frequent adjunct to the physical exam. Acetic acid 3%-5% soaked gauze is allowed to rest on the vulva for several minutes prior to observation with a colposcope or hand-held magnifying glass. Colposcopic findings are usually those of focal “white” epithelium. Vascular changes seen on the cervix (punctuation and mosaicism) are rarely seen on the vulva.

The entire anogenital region shares the same susceptibility to the HPV virus, thus squamous intraepithelial lesions are frequently multifocal. Physicians should have a heightened awareness of other lesions, such as cervical, vaginal, or anal, when managing a patient with VIN (Gynecol Oncol. 1995 Feb;56[2]:276-9). Appropriate cervical screening should be strictly adhered to and a thorough exam done at the time of vulvar colposcopy or exam.

Treatment

The goals of treatment include preventing carcinoma and improving symptoms while maintaining function and preserving anatomy. Treatment options for both types of VIN include excision, ablation, or medical therapy pending an evaluation of concurrent risk factors.

Premalignant disease was traditionally treated surgically. While surgical excision is still the mainstay of therapy, less aggressive techniques and medical therapy are more readily utilized. The goal of surgical excision for VIN is both diagnostic and therapeutic. When an excision for high-grade dysplasia is done (formerly VIN 3), detection of occult carcinoma was found in up to 3.2% in one large review (Gynecol Oncol. 2005;97:645-51).

Using a wide local excision to completely remove lesions with a pathologically clear margin reduces a patient’s risk of recurrence for disease compared to those excisions with positive margins (Obstet Gynecol. 1998;92:962-6). It is therefore critical that physicians carefully counsel patients who desire conservative therapy for VIN.

With any treatment, however, patients and physicians should be aware of the risk of recurrence; for vulvectomy, partial vulvectomy, local excision, and laser ablation, recurrences were seen at rates of 19%, 18%, 22%, and 23%, respectively, in a review of 3,322 patients (Gynecol Oncol. 2005;97:645-51).

CO₂ laser ablation has been used for single lesions as well as multifocal or confluent disease. Many physicians advocate for its use in patients with multifocal lesions as well as those with disease around the clitoris or anus, where excisional therapy is less desirable as laser therapy results in less scarring.

A 2015 Cochrane Database Review of medical therapy for high-grade dysplasia (usual-type VIN, VIN 2/3, or high-grade VIN) found that topical imiquimod can be used as a safe and effective option for high-grade VIN. Physicians should, however, be aware of unfavorable side effects that may require dose reductions. Cidofovir may be an alternative to imiquimod pending more evidence on long-term response and progression (Cochrane Database Syst Rev. 2015 Aug 18;8:CD007924). Topical 5-fluorouracil has fallen out of favor for VIN given its significant chemical desquamation, however response rates are thought to be favorable if tolerated.

As the use of VIN terminology solidifies and information emerges on medical therapy to treat VIN, it is critical that physicians remain current when counseling and providing treatment recommendations for vulvar intraepithelial neoplasia.

Dr. Gehrig is professor and director of gynecologic oncology 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 professor in the division of gynecologic oncology at the university. Dr. Sullivan is a fellow in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures. Email them at [email protected].

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.

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.

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 [email protected].

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 [email protected].

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 [email protected].