News for Your Practice

Not long ago, women with uterine fibroids had to choose between hysterectomy and abdominal myomectomy to alleviate their symptoms. Then came minimally invasive surgeries such as laparoscopic myomectomy and hysteroscopic myoma resection, although even now these surgeries are offered by a limited number of skilled gynecologic surgeons. And despite their substantially shorter recovery times, these procedures are still surgeries, with inherent complications. On top of that, long-term outcomes data are limited.

Enter the next generation of fibroid treatments: uterine artery embolization (UAE), focused ultrasound with magnetic resonance imaging (MRI) guidance, and selective progesterone receptor modulators—though the last option is still in the pipeline. Gynecologists will be seeing advertisements and promotional materials for these interventions in the near and not-so-distant future.

Uterine artery embolization: In the right hands, a worthwhile strategy

Myers ER, Goodwin S, Landow W, et al. Prospective data collection of a new procedure by a specialty society: the FIBROID Registry. Obstet Gynecol. 2005;106:44–51.

Worthington-Kirsch R, Spies JB, Myers ER, et al. The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short-term outcomes. Obstet Gynecol. 2005;106:52–59.

Congratulations are in order. When the Society of Interventional Radiology created the Fibroid Registry in 2000, it was looking for early data on UAE to share with patients. In its short but impressive life, the registry has collected more data about UAE than we have about “tried-and-true” surgeries.

In the United States, UAE was first used to treat fibroids in 1997. Although numerous studies since then have reported on its safety and effectiveness, many gynecologists continue to question the suitability of UAE for symptomatic women.

The Web-based registry was established with Duke Clinical Research Institute to track short- and long-term outcomes after UAE in various settings.

What we know from the registry

The Fibroid Registry enrolled its first patient in December 2000, and collected data from 72 sites on 3,319 UAE procedures through December 2002. The reports by Myers et al and Worthington-Kirsch and colleagues contain patient demographics, procedural details, and 30-day outcomes.

The registry defined adverse events as any unexpected event that necessitated an unscheduled office or emergency room visit or unanticipated therapy (medical or surgical). Major complications required increased care or additional hospitalization or had permanent adverse sequelae. Minor complications required medical management or no therapy.

Thirty-day outcomes were available for approximately 91% of patients.

A low complication rate

Complications were uncommon during the first 30 days after UAE, with a 1.1% incidence of additional surgery. In fact, complication rates and recovery times compared favorably with myomectomy and abdominal hysterectomy for large fibroids.

The UAE procedure averaged 56 minutes, with 96.2% technical success and a return to normal activities in about 2 weeks.

Other findings:

• 26% of patients had an adverse event, but only 4% had a major event, most commonly emergency care or hospital readmission for pain management (2.1%) or possible infection (<1%).
• 31 women required another procedure within 30 days, including 3 myomectomies, 9 dilatation and curettage procedures for sloughing leiomyomata, 5 hysteroscopic resections, and 3 hysterectomies for unrecorded indications.
• 1 patient was hospitalized for pain 10 days after UAE and underwent exploratory laparotomy with bilateral oophorectomy.
• The most common minor adverse events were hot flushes (5.7%) and pain requiring additional therapy (9.6%).

Predictors of adverse outcomes:

• current or recent smoking (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.007–1.293),
• African-American race (OR 1.129, 95% CI 1.019–1.251),
• prior procedures (OR 1.23, 95% CI 1.02–1.38), and
• duration of procedure (OR 1.004, 95% CI 1.001–1.006).

Interestingly, short-term outcomes did not differ among centers, nor did procedure times, length of stay, and incidence of adverse events during the first 30 days.

What to tell patients

I inform patients with symptomatic fibroids about all available treatments—including the option of doing nothing at all. Most have no interest in UAE, and are distressed by the thought of their bodies reabsorbing dead tissue.

However, I have had several patients whose operative risks were very high. For example, 1 woman was morbidly obese (>250 lb, which required her UAE treatment at a special facility equipped to perform fluoroscopy in morbidly obese patients), hypertensive, diabetic, and hemiparetic after a stroke. She was also a Jehovah’s Witness. Obviously, nonsurgical intervention was to her benefit. Her bleeding stopped almost immediately.

 

A reasonable alternative

The lay press recently focused on our obligation, as ObGyns, to inform patients about alternative therapies for fibroids. These first reports from the Fibroid Registry are clear: UAE is a reproducible, low-risk procedure—certainly lower in risk than complex surgeries (though situations may arise when myomectomy is preferred, such as a desire for future fertility¹).

The registry will continue to provide data we can share with our patients regarding risks, complications, and long-term outcomes. More importantly, our radiology colleagues have taken the lead in developing a voluntary patient registry to track the outcomes of new technology as it disseminates into the general medical community. Our patients would be well served if we developed similar registries to track our surgical outcomes.

Focused ultrasound shrinks fibroids, but has strict eligibility requirements

Hindley J, Gedroyc WM, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004;183:1713–1719.

Using MRI guidance, a completely noninvasive treatment is now possible: focused ultrasound ablation of uterine fibroids. This procedure, the newest high-tech treatment for symptomatic fibroids, was successfully tested in an earlier pilot study.² Although it eased symptoms to a remarkable degree during this phase III trial, how many women will ultimately be suitable for the treatment remains unclear.

Selection criteria

This trial of the ExAblate 2000 (InSightec, Tirat Carmel, Israel) recruited symptomatic women who were otherwise suitable candidates for conventional surgeries. Excluded were postmenopausal patients, women weighing more than 250 lb, and women who had a uterus larger than 24 weeks’ size or any single myoma larger than 10 cm. Women with extensive abdominal scars were carefully examined and excluded if the scars lay in the path of the ultrasound beam. The reason: During the earlier study, these scars tended to absorb ultrasound energy, increasing the risk of thermal injury at the skin surface.

Before proceeding, patients underwent MRI or ultrasound to confirm a clear pathway from the anterior abdominal wall to the fibroids without traversing the bladder or bowel.

Hindley et al did not reveal how many women were initially screened, but 109 were finally enrolled at 7 international sites and completed a Uterine Fibroid Symptoms and Quality of Life Questionnaire before and 3 and 6 months after treatment. As for the location of the fibroids: 22% were submucosal, 57% were intramural, and 21% were subserosal.

Up to 4 fibroids were treated per patient—with MRI mapping and thermographic monitoring—with a margin of 1.5 cm from the edge of the ablated area to the edge of the uterus. Conscious sedation was provided as needed, and tolerance of the procedure was measured using a 4-point pain scale. Mean time in the MRI scanner was 202 minutes (range, 90–370 minutes).

Pain stopped when treatment ended

Most women reported mild to moderate pain during the procedure (66%), and 16% complained of severe pain. This discomfort ended immediately when treatment stopped in virtually all patients—only 1% reported severe pain afterwards.

Adverse events

Serious adverse events included: 5 women with heavy menses requiring blood transfusions, 1 patient with pain and bleeding consistent with preprocedure symptoms, 1 woman needing overnight hospitalization for nausea related to opioid analgesia during the procedure, and 1 patient with leg and buttock pain immediately after treatment (it was later discovered that the sciatic nerve was in the far field of the sonication pathway). These symptoms resolved by the follow-up visit.

Two other patients had adverse events unrelated to the procedure.

6-month outcomes

The mean fibroid volume reduction was 13.5%±32%. Although this improvement seems modest, women reported significant relief from fibroid-related symptoms, and the mean severity score on the quality-of-life questionnaire decreased.

Substantial improvement was seen for both mass effect and bleeding symptoms (32.8 points out of 100 for each).

Pros and cons for symptomatic women

Advantages over UAE include the absence of postprocedural pain in almost all patients, which eliminates the need for an overnight stay and likely speeds the return to normal activities.

Disadvantages are that women with major abdominal scarring, anterior myomas underneath the bladder flap, or adhesive disease that causes small or large bowel to lie in the path of the sound waves cannot take advantage of this new technology, nor can women who have myomas close to neurovascular bundles. Add to that the extremely long procedure time (over 3 hours) and the modest reduction in uterine volume.

Six-month outcomes are promising, but this approach is probably best reserved for an academic setting, so careful screening and long-term tracking can continue.

A drug of great promise

 

Chwalisz K, Perez MC, Demanno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005;26:423–438.

In this comprehensive review, the authors draw from their extensive expertise in endocrinology to describe the rationale behind asoprisnil, a mixed progesterone receptor agonist/antagonist—the most promising pharmaceutical development in gynecology in several decades.

How the drug works

Mifepristone (RU-486) was the first progesterone receptor antagonist. Despite its ability to reduce myoma volume and suppress endometriosis symptoms in small pilot studies, it induces endometrial hyperplasia at doses higher than 5 to 10 mg, probably by acting similarly to unopposed estrogen. In contrast, asoprisnil has antiproliferative effects and no labor-inducing activity. It directly affects blood vessels in the endometrium, creating a local antiproliferative effect that induces amenorrhea despite normal estrogen levels.

What phase II studies reveal

A multicenter, double-blind, placebo-controlled trial involved 5-, 10-, and 25-mg daily doses of oral asoprisnil over 12 weeks. In a dose-dependent manner, asoprisnil induced amenorrhea or significantly suppressed bleeding without causing breakthrough or intermenstrual flow. It also decreased the volume of both the largest fibroid and the uterus as a whole. At 10- and 25-mg doses, pressure symptoms eased substantially over placebo. Adverse effects were minimal and affected the placebo and asoprisnil groups equally.

Phase III trials are now under way to assess the safety and efficacy of asoprisnil in the treatment of menorrhagia and uterine fibroids. Early results in the treatment of endometriosis are also promising.

What this means for fibroid patients

Though asoprisnil is not yet available for use, the phase III trial is winding down and the drug’s impressive potential seems clear.

A useful strategy may be to counsel marginally symptomatic women with fibroids that treatments are in the pipeline that would permit pharmaceutical management of their symptoms. Because this drug induces amenorrhea in the presence of normal circulating estrogen levels, it eliminates hot flushes and, more importantly, the bone loss associated with gonadotropin-releasing hormone agonists.

Disclosure

The author reports no financial relationships relevant to this article.

Not long ago, women with uterine fibroids had to choose between hysterectomy and abdominal myomectomy to alleviate their symptoms. Then came minimally invasive surgeries such as laparoscopic myomectomy and hysteroscopic myoma resection, although even now these surgeries are offered by a limited number of skilled gynecologic surgeons. And despite their substantially shorter recovery times, these procedures are still surgeries, with inherent complications. On top of that, long-term outcomes data are limited.

Enter the next generation of fibroid treatments: uterine artery embolization (UAE), focused ultrasound with magnetic resonance imaging (MRI) guidance, and selective progesterone receptor modulators—though the last option is still in the pipeline. Gynecologists will be seeing advertisements and promotional materials for these interventions in the near and not-so-distant future.

Uterine artery embolization: In the right hands, a worthwhile strategy

Myers ER, Goodwin S, Landow W, et al. Prospective data collection of a new procedure by a specialty society: the FIBROID Registry. Obstet Gynecol. 2005;106:44–51.

Worthington-Kirsch R, Spies JB, Myers ER, et al. The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short-term outcomes. Obstet Gynecol. 2005;106:52–59.

Congratulations are in order. When the Society of Interventional Radiology created the Fibroid Registry in 2000, it was looking for early data on UAE to share with patients. In its short but impressive life, the registry has collected more data about UAE than we have about “tried-and-true” surgeries.

In the United States, UAE was first used to treat fibroids in 1997. Although numerous studies since then have reported on its safety and effectiveness, many gynecologists continue to question the suitability of UAE for symptomatic women.

The Web-based registry was established with Duke Clinical Research Institute to track short- and long-term outcomes after UAE in various settings.

What we know from the registry

The Fibroid Registry enrolled its first patient in December 2000, and collected data from 72 sites on 3,319 UAE procedures through December 2002. The reports by Myers et al and Worthington-Kirsch and colleagues contain patient demographics, procedural details, and 30-day outcomes.

The registry defined adverse events as any unexpected event that necessitated an unscheduled office or emergency room visit or unanticipated therapy (medical or surgical). Major complications required increased care or additional hospitalization or had permanent adverse sequelae. Minor complications required medical management or no therapy.

Thirty-day outcomes were available for approximately 91% of patients.

A low complication rate

Complications were uncommon during the first 30 days after UAE, with a 1.1% incidence of additional surgery. In fact, complication rates and recovery times compared favorably with myomectomy and abdominal hysterectomy for large fibroids.

The UAE procedure averaged 56 minutes, with 96.2% technical success and a return to normal activities in about 2 weeks.

Other findings:

• 26% of patients had an adverse event, but only 4% had a major event, most commonly emergency care or hospital readmission for pain management (2.1%) or possible infection (<1%).
• 31 women required another procedure within 30 days, including 3 myomectomies, 9 dilatation and curettage procedures for sloughing leiomyomata, 5 hysteroscopic resections, and 3 hysterectomies for unrecorded indications.
• 1 patient was hospitalized for pain 10 days after UAE and underwent exploratory laparotomy with bilateral oophorectomy.
• The most common minor adverse events were hot flushes (5.7%) and pain requiring additional therapy (9.6%).

Predictors of adverse outcomes:

• current or recent smoking (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.007–1.293),
• African-American race (OR 1.129, 95% CI 1.019–1.251),
• prior procedures (OR 1.23, 95% CI 1.02–1.38), and
• duration of procedure (OR 1.004, 95% CI 1.001–1.006).

Interestingly, short-term outcomes did not differ among centers, nor did procedure times, length of stay, and incidence of adverse events during the first 30 days.

What to tell patients

I inform patients with symptomatic fibroids about all available treatments—including the option of doing nothing at all. Most have no interest in UAE, and are distressed by the thought of their bodies reabsorbing dead tissue.

However, I have had several patients whose operative risks were very high. For example, 1 woman was morbidly obese (>250 lb, which required her UAE treatment at a special facility equipped to perform fluoroscopy in morbidly obese patients), hypertensive, diabetic, and hemiparetic after a stroke. She was also a Jehovah’s Witness. Obviously, nonsurgical intervention was to her benefit. Her bleeding stopped almost immediately.

 

A reasonable alternative

The lay press recently focused on our obligation, as ObGyns, to inform patients about alternative therapies for fibroids. These first reports from the Fibroid Registry are clear: UAE is a reproducible, low-risk procedure—certainly lower in risk than complex surgeries (though situations may arise when myomectomy is preferred, such as a desire for future fertility¹).

The registry will continue to provide data we can share with our patients regarding risks, complications, and long-term outcomes. More importantly, our radiology colleagues have taken the lead in developing a voluntary patient registry to track the outcomes of new technology as it disseminates into the general medical community. Our patients would be well served if we developed similar registries to track our surgical outcomes.

Focused ultrasound shrinks fibroids, but has strict eligibility requirements

Hindley J, Gedroyc WM, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004;183:1713–1719.

Using MRI guidance, a completely noninvasive treatment is now possible: focused ultrasound ablation of uterine fibroids. This procedure, the newest high-tech treatment for symptomatic fibroids, was successfully tested in an earlier pilot study.² Although it eased symptoms to a remarkable degree during this phase III trial, how many women will ultimately be suitable for the treatment remains unclear.

Selection criteria

This trial of the ExAblate 2000 (InSightec, Tirat Carmel, Israel) recruited symptomatic women who were otherwise suitable candidates for conventional surgeries. Excluded were postmenopausal patients, women weighing more than 250 lb, and women who had a uterus larger than 24 weeks’ size or any single myoma larger than 10 cm. Women with extensive abdominal scars were carefully examined and excluded if the scars lay in the path of the ultrasound beam. The reason: During the earlier study, these scars tended to absorb ultrasound energy, increasing the risk of thermal injury at the skin surface.

Before proceeding, patients underwent MRI or ultrasound to confirm a clear pathway from the anterior abdominal wall to the fibroids without traversing the bladder or bowel.

Hindley et al did not reveal how many women were initially screened, but 109 were finally enrolled at 7 international sites and completed a Uterine Fibroid Symptoms and Quality of Life Questionnaire before and 3 and 6 months after treatment. As for the location of the fibroids: 22% were submucosal, 57% were intramural, and 21% were subserosal.

Up to 4 fibroids were treated per patient—with MRI mapping and thermographic monitoring—with a margin of 1.5 cm from the edge of the ablated area to the edge of the uterus. Conscious sedation was provided as needed, and tolerance of the procedure was measured using a 4-point pain scale. Mean time in the MRI scanner was 202 minutes (range, 90–370 minutes).

Pain stopped when treatment ended

Most women reported mild to moderate pain during the procedure (66%), and 16% complained of severe pain. This discomfort ended immediately when treatment stopped in virtually all patients—only 1% reported severe pain afterwards.

Adverse events

Serious adverse events included: 5 women with heavy menses requiring blood transfusions, 1 patient with pain and bleeding consistent with preprocedure symptoms, 1 woman needing overnight hospitalization for nausea related to opioid analgesia during the procedure, and 1 patient with leg and buttock pain immediately after treatment (it was later discovered that the sciatic nerve was in the far field of the sonication pathway). These symptoms resolved by the follow-up visit.

Two other patients had adverse events unrelated to the procedure.

6-month outcomes

The mean fibroid volume reduction was 13.5%±32%. Although this improvement seems modest, women reported significant relief from fibroid-related symptoms, and the mean severity score on the quality-of-life questionnaire decreased.

Substantial improvement was seen for both mass effect and bleeding symptoms (32.8 points out of 100 for each).

Pros and cons for symptomatic women

Advantages over UAE include the absence of postprocedural pain in almost all patients, which eliminates the need for an overnight stay and likely speeds the return to normal activities.

Disadvantages are that women with major abdominal scarring, anterior myomas underneath the bladder flap, or adhesive disease that causes small or large bowel to lie in the path of the sound waves cannot take advantage of this new technology, nor can women who have myomas close to neurovascular bundles. Add to that the extremely long procedure time (over 3 hours) and the modest reduction in uterine volume.

Six-month outcomes are promising, but this approach is probably best reserved for an academic setting, so careful screening and long-term tracking can continue.

A drug of great promise

 

Chwalisz K, Perez MC, Demanno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005;26:423–438.

In this comprehensive review, the authors draw from their extensive expertise in endocrinology to describe the rationale behind asoprisnil, a mixed progesterone receptor agonist/antagonist—the most promising pharmaceutical development in gynecology in several decades.

How the drug works

Mifepristone (RU-486) was the first progesterone receptor antagonist. Despite its ability to reduce myoma volume and suppress endometriosis symptoms in small pilot studies, it induces endometrial hyperplasia at doses higher than 5 to 10 mg, probably by acting similarly to unopposed estrogen. In contrast, asoprisnil has antiproliferative effects and no labor-inducing activity. It directly affects blood vessels in the endometrium, creating a local antiproliferative effect that induces amenorrhea despite normal estrogen levels.

What phase II studies reveal

A multicenter, double-blind, placebo-controlled trial involved 5-, 10-, and 25-mg daily doses of oral asoprisnil over 12 weeks. In a dose-dependent manner, asoprisnil induced amenorrhea or significantly suppressed bleeding without causing breakthrough or intermenstrual flow. It also decreased the volume of both the largest fibroid and the uterus as a whole. At 10- and 25-mg doses, pressure symptoms eased substantially over placebo. Adverse effects were minimal and affected the placebo and asoprisnil groups equally.

Phase III trials are now under way to assess the safety and efficacy of asoprisnil in the treatment of menorrhagia and uterine fibroids. Early results in the treatment of endometriosis are also promising.

What this means for fibroid patients

Though asoprisnil is not yet available for use, the phase III trial is winding down and the drug’s impressive potential seems clear.

A useful strategy may be to counsel marginally symptomatic women with fibroids that treatments are in the pipeline that would permit pharmaceutical management of their symptoms. Because this drug induces amenorrhea in the presence of normal circulating estrogen levels, it eliminates hot flushes and, more importantly, the bone loss associated with gonadotropin-releasing hormone agonists.

Disclosure

The author reports no financial relationships relevant to this article.

Not long ago, women with uterine fibroids had to choose between hysterectomy and abdominal myomectomy to alleviate their symptoms. Then came minimally invasive surgeries such as laparoscopic myomectomy and hysteroscopic myoma resection, although even now these surgeries are offered by a limited number of skilled gynecologic surgeons. And despite their substantially shorter recovery times, these procedures are still surgeries, with inherent complications. On top of that, long-term outcomes data are limited.

Enter the next generation of fibroid treatments: uterine artery embolization (UAE), focused ultrasound with magnetic resonance imaging (MRI) guidance, and selective progesterone receptor modulators—though the last option is still in the pipeline. Gynecologists will be seeing advertisements and promotional materials for these interventions in the near and not-so-distant future.

Uterine artery embolization: In the right hands, a worthwhile strategy

Myers ER, Goodwin S, Landow W, et al. Prospective data collection of a new procedure by a specialty society: the FIBROID Registry. Obstet Gynecol. 2005;106:44–51.

Worthington-Kirsch R, Spies JB, Myers ER, et al. The Fibroid Registry for outcomes data (FIBROID) for uterine embolization: short-term outcomes. Obstet Gynecol. 2005;106:52–59.

Congratulations are in order. When the Society of Interventional Radiology created the Fibroid Registry in 2000, it was looking for early data on UAE to share with patients. In its short but impressive life, the registry has collected more data about UAE than we have about “tried-and-true” surgeries.

In the United States, UAE was first used to treat fibroids in 1997. Although numerous studies since then have reported on its safety and effectiveness, many gynecologists continue to question the suitability of UAE for symptomatic women.

The Web-based registry was established with Duke Clinical Research Institute to track short- and long-term outcomes after UAE in various settings.

What we know from the registry

The Fibroid Registry enrolled its first patient in December 2000, and collected data from 72 sites on 3,319 UAE procedures through December 2002. The reports by Myers et al and Worthington-Kirsch and colleagues contain patient demographics, procedural details, and 30-day outcomes.

The registry defined adverse events as any unexpected event that necessitated an unscheduled office or emergency room visit or unanticipated therapy (medical or surgical). Major complications required increased care or additional hospitalization or had permanent adverse sequelae. Minor complications required medical management or no therapy.

Thirty-day outcomes were available for approximately 91% of patients.

A low complication rate

Complications were uncommon during the first 30 days after UAE, with a 1.1% incidence of additional surgery. In fact, complication rates and recovery times compared favorably with myomectomy and abdominal hysterectomy for large fibroids.

The UAE procedure averaged 56 minutes, with 96.2% technical success and a return to normal activities in about 2 weeks.

Other findings:

• 26% of patients had an adverse event, but only 4% had a major event, most commonly emergency care or hospital readmission for pain management (2.1%) or possible infection (<1%).
• 31 women required another procedure within 30 days, including 3 myomectomies, 9 dilatation and curettage procedures for sloughing leiomyomata, 5 hysteroscopic resections, and 3 hysterectomies for unrecorded indications.
• 1 patient was hospitalized for pain 10 days after UAE and underwent exploratory laparotomy with bilateral oophorectomy.
• The most common minor adverse events were hot flushes (5.7%) and pain requiring additional therapy (9.6%).

Predictors of adverse outcomes:

• current or recent smoking (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.007–1.293),
• African-American race (OR 1.129, 95% CI 1.019–1.251),
• prior procedures (OR 1.23, 95% CI 1.02–1.38), and
• duration of procedure (OR 1.004, 95% CI 1.001–1.006).

Interestingly, short-term outcomes did not differ among centers, nor did procedure times, length of stay, and incidence of adverse events during the first 30 days.

What to tell patients

I inform patients with symptomatic fibroids about all available treatments—including the option of doing nothing at all. Most have no interest in UAE, and are distressed by the thought of their bodies reabsorbing dead tissue.

However, I have had several patients whose operative risks were very high. For example, 1 woman was morbidly obese (>250 lb, which required her UAE treatment at a special facility equipped to perform fluoroscopy in morbidly obese patients), hypertensive, diabetic, and hemiparetic after a stroke. She was also a Jehovah’s Witness. Obviously, nonsurgical intervention was to her benefit. Her bleeding stopped almost immediately.

 

A reasonable alternative

The lay press recently focused on our obligation, as ObGyns, to inform patients about alternative therapies for fibroids. These first reports from the Fibroid Registry are clear: UAE is a reproducible, low-risk procedure—certainly lower in risk than complex surgeries (though situations may arise when myomectomy is preferred, such as a desire for future fertility¹).

The registry will continue to provide data we can share with our patients regarding risks, complications, and long-term outcomes. More importantly, our radiology colleagues have taken the lead in developing a voluntary patient registry to track the outcomes of new technology as it disseminates into the general medical community. Our patients would be well served if we developed similar registries to track our surgical outcomes.

Focused ultrasound shrinks fibroids, but has strict eligibility requirements

Hindley J, Gedroyc WM, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004;183:1713–1719.

Using MRI guidance, a completely noninvasive treatment is now possible: focused ultrasound ablation of uterine fibroids. This procedure, the newest high-tech treatment for symptomatic fibroids, was successfully tested in an earlier pilot study.² Although it eased symptoms to a remarkable degree during this phase III trial, how many women will ultimately be suitable for the treatment remains unclear.

Selection criteria

This trial of the ExAblate 2000 (InSightec, Tirat Carmel, Israel) recruited symptomatic women who were otherwise suitable candidates for conventional surgeries. Excluded were postmenopausal patients, women weighing more than 250 lb, and women who had a uterus larger than 24 weeks’ size or any single myoma larger than 10 cm. Women with extensive abdominal scars were carefully examined and excluded if the scars lay in the path of the ultrasound beam. The reason: During the earlier study, these scars tended to absorb ultrasound energy, increasing the risk of thermal injury at the skin surface.

Before proceeding, patients underwent MRI or ultrasound to confirm a clear pathway from the anterior abdominal wall to the fibroids without traversing the bladder or bowel.

Hindley et al did not reveal how many women were initially screened, but 109 were finally enrolled at 7 international sites and completed a Uterine Fibroid Symptoms and Quality of Life Questionnaire before and 3 and 6 months after treatment. As for the location of the fibroids: 22% were submucosal, 57% were intramural, and 21% were subserosal.

Up to 4 fibroids were treated per patient—with MRI mapping and thermographic monitoring—with a margin of 1.5 cm from the edge of the ablated area to the edge of the uterus. Conscious sedation was provided as needed, and tolerance of the procedure was measured using a 4-point pain scale. Mean time in the MRI scanner was 202 minutes (range, 90–370 minutes).

Pain stopped when treatment ended

Most women reported mild to moderate pain during the procedure (66%), and 16% complained of severe pain. This discomfort ended immediately when treatment stopped in virtually all patients—only 1% reported severe pain afterwards.

Adverse events

Serious adverse events included: 5 women with heavy menses requiring blood transfusions, 1 patient with pain and bleeding consistent with preprocedure symptoms, 1 woman needing overnight hospitalization for nausea related to opioid analgesia during the procedure, and 1 patient with leg and buttock pain immediately after treatment (it was later discovered that the sciatic nerve was in the far field of the sonication pathway). These symptoms resolved by the follow-up visit.

Two other patients had adverse events unrelated to the procedure.

6-month outcomes

The mean fibroid volume reduction was 13.5%±32%. Although this improvement seems modest, women reported significant relief from fibroid-related symptoms, and the mean severity score on the quality-of-life questionnaire decreased.

Substantial improvement was seen for both mass effect and bleeding symptoms (32.8 points out of 100 for each).

Pros and cons for symptomatic women

Advantages over UAE include the absence of postprocedural pain in almost all patients, which eliminates the need for an overnight stay and likely speeds the return to normal activities.

Disadvantages are that women with major abdominal scarring, anterior myomas underneath the bladder flap, or adhesive disease that causes small or large bowel to lie in the path of the sound waves cannot take advantage of this new technology, nor can women who have myomas close to neurovascular bundles. Add to that the extremely long procedure time (over 3 hours) and the modest reduction in uterine volume.

Six-month outcomes are promising, but this approach is probably best reserved for an academic setting, so careful screening and long-term tracking can continue.

A drug of great promise

 

Chwalisz K, Perez MC, Demanno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005;26:423–438.

In this comprehensive review, the authors draw from their extensive expertise in endocrinology to describe the rationale behind asoprisnil, a mixed progesterone receptor agonist/antagonist—the most promising pharmaceutical development in gynecology in several decades.

How the drug works

Mifepristone (RU-486) was the first progesterone receptor antagonist. Despite its ability to reduce myoma volume and suppress endometriosis symptoms in small pilot studies, it induces endometrial hyperplasia at doses higher than 5 to 10 mg, probably by acting similarly to unopposed estrogen. In contrast, asoprisnil has antiproliferative effects and no labor-inducing activity. It directly affects blood vessels in the endometrium, creating a local antiproliferative effect that induces amenorrhea despite normal estrogen levels.

What phase II studies reveal

A multicenter, double-blind, placebo-controlled trial involved 5-, 10-, and 25-mg daily doses of oral asoprisnil over 12 weeks. In a dose-dependent manner, asoprisnil induced amenorrhea or significantly suppressed bleeding without causing breakthrough or intermenstrual flow. It also decreased the volume of both the largest fibroid and the uterus as a whole. At 10- and 25-mg doses, pressure symptoms eased substantially over placebo. Adverse effects were minimal and affected the placebo and asoprisnil groups equally.

Phase III trials are now under way to assess the safety and efficacy of asoprisnil in the treatment of menorrhagia and uterine fibroids. Early results in the treatment of endometriosis are also promising.

What this means for fibroid patients

Though asoprisnil is not yet available for use, the phase III trial is winding down and the drug’s impressive potential seems clear.

A useful strategy may be to counsel marginally symptomatic women with fibroids that treatments are in the pipeline that would permit pharmaceutical management of their symptoms. Because this drug induces amenorrhea in the presence of normal circulating estrogen levels, it eliminates hot flushes and, more importantly, the bone loss associated with gonadotropin-releasing hormone agonists.

Disclosure

The author reports no financial relationships relevant to this article.

Unfortunate but true: Many complications of pelvic surgery involve injury to the lower urinary tract—and many of these injuries go undetected and increase the patient’s risk of serious morbidity and the physician’s chances of being sued.

Even more unfortunate: These injuries are on the rise, thanks to the proliferation of anti-incontinence surgeries, greater use of laparoscopy, and the need for increasingly complex vaginal dissection.

Fortunately, most lower urinary tract injuries can be avoided, or at least detected early, and this discussion centers on techniques to accomplish those goals and ensure bladder integrity and ureteral patency.

The rising injury rate

There appear to be more injuries to the lower urinary tract arising from pelvic surgery. Why do you think that is?

BARBER: I think the increase is due to the increasing popularity of midurethral slings, such as the tension-free vaginal tape (TVT). With these blind retropubic procedures, the risk of bladder injury is approximately 5%, which is considerably higher than in most other procedures we perform.¹

Fortunately, the negative consequences of placing the TVT trocar into the dome of the bladder are minimal, since the trocar can be removed and placed in the appropriate location without the need for bladder repair and without causing long-term bladder dysfunction.

KARRAM: The higher rate of injury also may be linked, in part, to greater use of energy sources during laparoscopic surgery. Over the past 2 years, we have seen numerous cases of delayed injury to the lower urinary tract or bowel secondary to thermal damage from energy devices including electrosurgical instruments and ultrasonic shears.

BARBER: I think there is an increase in lower urinary tract and ureteral injury because of the rising popularity of operative laparoscopy. Lower urinary tract injury is certainly more common with laparoscopic hysterectomy than with abdominal or vaginal hysterectomy.

Increase has no single cause

BENT: There may be a small increase overall in lower urinary tract injury during pelvic surgery, since we now do more procedures that require complicated vaginal dissection and exploration of tissue planes in close proximity to the ureters. This has increased the rate of ureteral injuries.

There also have been a few more urethral injuries, again related to tension-free suburethral slings, most often involving the transobturator approach.

KARRAM: The higher rate of cesarean sections also plays a role. Many women undergoing hysterectomies have had 1 or more cesarean deliveries. We recently completed a study that shows that cesarean section is an independent risk factor for cystotomy at the time of hysterectomy.²

Unfortunately, many surgeons still use aggressive blunt dissection when they attempt to mobilize the bladder off the uterus—whether a hysterectomy is being performed abdominally or vaginally. This can lead to inadvertent entry into the bladder. For this reason, sharp dissection should always be used.

CUNDIFF: Based on my reading of the literature, the incidence of operative injury to the lower urinary tract during gynecologic surgery in general has not changed noticeably since Samson reviewed the subject in 1902³—although gynecologic surgery is the leading cause of such injuries and the leading cause of litigation against gynecologists.⁴

Most injuries involve hysterectomy

CUNDIFF: Most injuries occur during straightforward hysterectomies. Estimates of the prevalence of ureteral injury range from 0.4% to 2.4%.^5-8 Since most studies estimating prevalence have not evaluated the lower urinary tract in the whole study population, they may underestimate true prevalence. However, a recent study by Vakili and colleagues⁹ included universal endoscopy of all patients undergoing hysterectomy and reported rates of ureteral injury (1.7%) and bladder injury (3.6%) similar to those of less rigorous studies.

 

Overall, the incidence of lower urinary tract injury during other types of urogynecologic surgery is higher than during hysterectomy. Evidence of the higher prevalence during urogynecologic surgery comes from several recent studies. Harris et al¹⁰ reported a 5.7% injury rate during reconstructive surgery for incontinence or prolapse. Importantly, 4% were unrecognized prior to urinary tract endoscopy.

Procedures most commonly associated with urinary tract injury were retropubic urethropexy and apical prolapse procedures using the uterosacral ligament in this series. This higher prevalence in urogynecologic procedures may explain the perceived increase in injuries overall.

How can a surgeon prevent bladder or ureteral injury during open hysterectomy?

BENT: Any procedure—regardless of the approach—demands careful dissection, good lighting, and exposure of appropriate structures. It is hard to avoid what you cannot see!

CUNDIFF: When I enter the peritoneal cavity, especially in patients undergoing reoperation, I make the incision more superiorly and avoid the bladder when extending the incision inferiorly. I always open the pararectal space and identify the ureters to ensure their safety during clamping.

Dissection of the vesicovaginal space is most effective when it is done sharply with adequate traction and countertraction. This can be achieved by gently pulling the bladder anteriorly with a Babcock clamp, using scissors to dissect close to the cervix.

For very large fundi, dissection of the vesicovaginal space can be difficult if the uterus is brought through the laparotomy. In these cases I generally take the round ligaments and infundibulopelvic ligaments first and then push the fundus into the upper abdomen. This helps keep the bowel out of the field and gives better visualization of the vesicovaginal space.

I generally enter the anterior fornix with a scalpel and then use Jorgensen scissors to excise the cervix. This helps protect the bladder, and also maximizes vaginal length.

By the way, I use a modified lithotomy position with universal stirrups to maintain access to the bladder for cystoscopy, in case it is needed later.

Follow the ureter

BARBER: During abdominal hysterectomy, I routinely identify the course of the ureter in the retroperitoneum and follow it from where it enters the pelvis until it disappears into the cardinal ligament and below the uterine artery. Following its course helps me avoid ureteral injury.

BENT: If there is scarring of the tube or ovary, or a mass is present, the ureter may have to be localized and dissected completely free of the adnexal structures before any clamps are placed. In addition, the bladder flap should routinely be mobilized using sharp dissection, never blunt dissection.

Mobilization of the bladder downward also pushes the ureters further out of the way during clamping of the uterine vessels. If bleeding occurs, secure hemostasis after observing the location of the ureters. If there is any concern about injury, cystoscopy with injected dye is required.

Next, as the uterosacral and cardinal ligaments are approached, the bladder must be reflected well inferior to this area. This will keep the ureters somewhat removed from the clamps.

Other tricks include performing intrafascial hysterectomy, in which the fascia is peeled away from the uterus and cervix, protecting the ureters.

Clamps placed across the cardinal and uterosacral ligament complexes must hug the uterus and roll off the cervix to protect the ureter.

When the cuff is sutured after removal of the uterus, clear planes of vagina must be seen anteriorly and posteriorly to avoid suturing the bladder into the vaginal cuff.

3 preventive strategies

KARRAM: For abdominal hysterectomy, I recommend 3 techniques:

• Skeletonize the infundibulopelvic ligament. Most surgeons do this routinely during the abdominal approach; I also recommend it for laparoscopic hysterectomy. Once there is a window in the broad ligament and the infundibulopelvic ligament is skeletonized, one can be sure the ureter is well below this area and probably out of harm’s way.
• Use sharp dissection to mobilize the bladder off the anterior cervix.
• Maintain awareness of the close proximity of the lower ureter to the uterosacral cardinal ligament. As the ureter enters the bladder, it can be as close as 1 cm lateral to the uterosacral ligament. This is an area where it is almost impossible to dissect out the ureter, so the surgeon needs to appreciate this anatomy and refrain from taking aggressive bites in the lateral direction when supporting or closing the vaginal cuff.

How can a surgeon prevent bladder or ureteral injury during laparoscopic hysterectomy?

BARBER: I think the ureter is best identified by direct visualization transperitoneally. The angle of the laparoscope makes visualizing the ureter much easier than from an abdominal approach, so retroperitoneal dissection is not necessary as often.

 

If the course of the ureter is not readily identified by direct transperitoneal visualization, a peritoneal incision can be made below and parallel to the infundibulopelvic ligament, which allows entry into the retroperitoneum and, typically, easy visualization of the ureter throughout its course.

Alternatively, the retroperitoneum can be entered lateral to the infundibulopelvic ligament, and the ureter can be identified in the same manner as in abdominal hysterectomy.

If laparoscopically assisted hysterectomy is planned, I prefer to dissect the bladder flap vaginally rather than laparoscopically, as the risk of bladder injury is considerably lower from a vaginal approach than it is laparoscopically. Obviously, if a total laparoscopic hysterectomy is necessary because of poor vaginal access, laparoscopic bladder flap dissection is necessary. In this case, I again favor sharp dissection and minimal use of cautery to avoid bladder injury.

How can a surgeon prevent bladder or ureteral injury during vaginal hysterectomy?

BENT: Traditional methods in which each clamp is rolled off the cervix or uterus until the procedure is completed help keep unsuspecting surgeons out of the bladder and away from the ureter. The only risk involves bladder mobilization (ie, creation of the bladder flap), which should always be done sharply to prevent bladder perforation. Avoid blunt finger or sponge-stick dissection! Knowing how to sharply dissect the bladder flap is vital—then even cases of prior cesarean section are manageable.

Salpingo-oophorectomy can also proceed under direct vision. Avoid the ureter by making sure the clamp closes only over the pedicles of the tube and ovary, with no intervening tissues in the clamp. If space is very tight, divide the round ligament and take the pedicle in a smaller bite. Traction on the cervix during the procedure, and mobilization of the bladder, allow the ureters to slide upward, well out of harm’s way, as the procedure progresses.

The importance of sharp dissection

BARBER: During vaginal hysterectomy, I usually have the operative assistant hold the cervical tenaculum so that there is tension on the uterus. I then use forceps to elevate the bladder directly vertically in order to place the bladder fibers on tension. Next, I dissect the bladder off the cervix and lower uterine segment using sharp dissection, and identify the peritoneum by direct finger palpation. Almost always, it is smooth and slippery.

After identifying the peritoneum, I grasp it with a tonsil clamp and elevate it so that it can be entered easily with scissors. I always confirm peritoneal entry by visualizing and identifying intraperitoneal structures such as bowel fat, the uterine serosal surface, or adnexae.

Some people advocate palpating the ureter during vaginal cases.

CUNDIFF: The most common time of injury during vaginal hysterectomy is during dissection of the vesicovaginal space; and suture ligation of the infundibulopelvic ligaments and uterine arteries carries the greatest potential for ureteral injury.

During vaginal hysterectomy, I try to dissect the vesicovaginal space early. I use a Deever retractor to retract the bladder anteriorly, maximizing my ability to sharply dissect close to the cervix until entering the peritoneal cavity. Once I’m in the peritoneal cavity, I advance the Deever retractor to protect the bladder through the rest of the procedure. I maximize protection of the ureters by applying downward traction on the cervix during vaginal clamp placement.

KARRAM: I agree. Never try to enter the anterior cul-de-sac until the vesicouterine space has been identified and is easily palpated. Rushing to enter the anterior cul-de-sac will only lead to inadvertent cystotomy.

Assessing ureteral patency

After what pelvic surgeries do you think ureteral patency should be assessed, and how should it be accomplished?

CUNDIFF: The literature contains several studies^10-13 that involved universal endoscopy of the lower urinary tract. These studies demonstrate that most injuries are not recognized by the surgeon prior to endoscopy. In fact, the vast majority of injuries occur after straightforward hysterectomies. This may be due in part to the sheer volume of hysterectomies, compared with other pelvic surgeries. However, it also shows that, when lower urinary tract evaluation is performed solely when the surgeon suspects an injury, a substantial proportion of injuries are missed.

KARRAM: When do you assess ureteral patency?

CUNDIFF: My personal practice is to evaluate it in all cases that carry the potential for injury to the ureter. The complexity of the evaluation is proportional to the probability of ureteral injury.

For all laparotomies and laparoscopies, I identify the course of the ureter and confirm peristalsis. In the simplest of cases, this can be done by identifying the ureter beneath the peritoneum as it crosses the pelvic brim and courses across the pelvic sidewall. More frequently, it involves opening the pararectal space to identify the course of the ureter. In the most complex cases, it requires ureterolysis.

 

I strongly believe that identifying the ureter during any dissection that endangers it is the best way to avoid injury. Even after these precautions, I frequently perform cystoscopy with intravenous indigo carmine to confirm ureteral patency. This is my standard approach with all vaginal procedures, as I am not confident that I can palpate the course of the ureter.

Postoperative cystoscopy is virtually without morbidity and adds no more than 3 minutes to the procedure when properly planned. It also affords an excellent opportunity to train residents in cystoscopy.

How to assess patency after selected procedures

BENT: Ureteral patency should be assured after any repair of the pelvic floor.

After abdominal hysterectomy, if there is blood in the catheter bag or any difficulty has been encountered during surgery, I perform cystoscopy after injecting indigo carmine dye, to observe ureteral function.

At abdominal or laparoscopic sacrocolpopexy, I follow the path of the ureters over the pelvic brim and inferiorly to the adnexal area by direct inspection.

During abdominal or laparoscopic paravaginal repair, the Burch procedure, or uterosacral ligament suspension, I perform cystoscopy after tying sutures and injecting indigo carmine to ensure ureteral function.

To safeguard the ureter, follow its course

Vaginal hysterectomy is not usually associated with ureteral injury, and very uncommonly with bladder injury. However, if bladder injury is observed or the procedure has been difficult, it is wise to perform cystoscopy with dye injection. This also extends to traditional cystocele repair.

I also recommend cystoscopy with dye injection any time there is a vaginal approach to paravaginal defect repair, vault suspension, or colpocleisis.

Cystoscopy—safe, simple, and efficient

KARRAM: For vaginal surgery, I think cystoscopy is the simplest way to assess the lower urinary tract. I routinely use it after any procedures involving the posterior cul-de-sac such as McCall culdoplasty or vaginal vault suspension from the uterosacral ligaments. I also use it routinely after advanced prolapse repairs involving anterior colporrhaphy, as well as paravaginal defect repairs, and I certainly use it routinely after any lower urinary tract reconstructive procedures such as fistula repairs.

As for laparoscopic surgery, I think cystoscopy is again the most efficient way to assess the lower urinary tract. I do so after any retropubic suspension, be it a Burch colposuspension or a paravaginal repair, any type of vault suspension or sacrocolpopexy, and any type of hysterectomy or adnexectomy that involves dissection of the retroperitoneal space. I also do so if an energy source was used extensively in the vicinity of the retroperitoneal space on either side.

After abdominal surgery, it is probably more efficient (assuming the patient is not in stirrups) to perform a high extraperitoneal cystotomy or suprapubic telescopy. The indications are any difficult dissection in which I have concerns about ureteral patency, as well as any abdominal prolapse or anti-incontinence procedures.

Ureteral stenting

Is ureteral stenting ever indicated preoperatively? If so, when?

BARBER: I do not think ureteral stenting is indicated routinely for any procedure. There may be individual cases where a stent may help the surgeon avoid ureteral injury, but I can’t think of a procedure in which it should be routinely used.

CUNDIFF: I agree. Although ureteral stenting is an important tool for the pelvic floor surgeon to investigate potential ureteral obstruction, I think it has very limited value as a preoperative maneuver to avoid injury. My opinion is based on the following observations:

The surgeon cannot really assess the potential difficulty of identifying the course of the ureter until the peritoneal cavity is entered.

For the truly hostile pelvis, in which pelvic sidewall pathology prevents identification of the course of the ureter, I do not find that a stent facilitates dissection of the pararectal space and ureterolysis. In fact, it could increase the chance of ureteral injury by creating a backboard against which to cut it during dissection.

Any potential benefit of ureteral stents—which I believe is minimal—must be balanced against the potential risks, which include 20 to 30 minutes of added OR time and the risk of ureteral spasm or perforation.

BENT: I also agree that ureteral stenting is seldom helpful during gynecologic surgery. At laparotomy, direct dissection of the structures and exposure of the ureter are best; there is no need to feel for a ureter.

At laparoscopy, however, if there are large fibroids, scarring from endometriomas, or adnexal masses, then preoperative placement of lighted stents can help the surgeon identify the ureters during dissection. The case would still require dissection of the ureter away from the operative field, but the lighted path provides a starting point in this procedure.

 

For vaginal surgical procedures, it is easier to avoid the ureter. However, not all surgeons can palpate a nonstented ureter, which may be required during a high uterosacral ligament suspension. A stent can readily take the surgeon to the ureter and avoid injury in most cases. This may be helpful for less experienced operators.

What should residents be trained to do?

Do most obstetrics and gynecology residency programs appropriately train young physicians to evaluate and manage lower urinary tract injury during pelvic surgery?

CUNDIFF: I am afraid not. Although residency directors increasingly recognize the importance of educating doctors to prevent and manage these injuries, this recognition has not yet risen to the policy level.

For example, the Council on Resident Education in Obstetrics and Gynecology (CREOG) includes a bladder surgery educational model that necessitates dissection of the ureter, cystoscopy, ureteral stenting, bladder repair, and ureteral reanastomosis.

However, the CREOG surgical curriculum makes no mention of protecting or evaluating the lower urinary tract during pelvic surgery.

This spectrum seems to reflect the wide variation among residency programs, too. While some programs such as ours at Johns Hopkins provide comprehensive training in prevention, evaluation, and management of lower urinary tract injury, many others do not. This might be because some programs lack technically skilled faculty. Interdisciplinary politics also likely influences local credentialing.

BARBER: In my opinion, a graduating ObGyn resident should be able to:

• identify and mobilize the ureter to avoid injury during abdominal and laparoscopic surgery
• safely mobilize the bladder during abdominal, vaginal, or laparoscopic hysterectomy
• perform intraoperative cystoscopy to evaluate for injury
• repair bladder injuries abdominally and vaginally

However, I don’t think it is realistic for a graduating resident to be able to manage ureteral injuries, as residents are unlikely to encounter very many during training. These injuries are best left to our urology colleagues.

BENT: Very little or no education is provided in preventing lower urinary tract injury; evaluation is better managed in many programs. A conservative estimate is that 20% of programs have a reasonable curriculum for preoperative assessment and evaluation of incontinence and prolapse.

The management of pelvic floor disorders is better handled in almost all programs, especially as it relates to surgery. Many residents spend a lot of time on the urogynecology service and are exposed to the surgical aspect of rotations.

Dr. Karram and Dr. Barber have no financial relationships relevant to this article. Dr. Bent serves on the gynecology advisory board of ACMI and is a speaker for Novartis, Pfizer, Watson, and Asetellas (formerly Yamanouchi). He also has received research funding from Cook, Eli Lilly, and Mentor; and is a consultant for C.R. Bard. Dr. Cundiff has received grant/research support from Cook, is a consultant to C.R. Bard and Eli Lilly, and is a speaker for GlaxoSmithKline.

Unfortunate but true: Many complications of pelvic surgery involve injury to the lower urinary tract—and many of these injuries go undetected and increase the patient’s risk of serious morbidity and the physician’s chances of being sued.

Even more unfortunate: These injuries are on the rise, thanks to the proliferation of anti-incontinence surgeries, greater use of laparoscopy, and the need for increasingly complex vaginal dissection.

Fortunately, most lower urinary tract injuries can be avoided, or at least detected early, and this discussion centers on techniques to accomplish those goals and ensure bladder integrity and ureteral patency.

The rising injury rate

There appear to be more injuries to the lower urinary tract arising from pelvic surgery. Why do you think that is?

BARBER: I think the increase is due to the increasing popularity of midurethral slings, such as the tension-free vaginal tape (TVT). With these blind retropubic procedures, the risk of bladder injury is approximately 5%, which is considerably higher than in most other procedures we perform.¹

Fortunately, the negative consequences of placing the TVT trocar into the dome of the bladder are minimal, since the trocar can be removed and placed in the appropriate location without the need for bladder repair and without causing long-term bladder dysfunction.

KARRAM: The higher rate of injury also may be linked, in part, to greater use of energy sources during laparoscopic surgery. Over the past 2 years, we have seen numerous cases of delayed injury to the lower urinary tract or bowel secondary to thermal damage from energy devices including electrosurgical instruments and ultrasonic shears.

BARBER: I think there is an increase in lower urinary tract and ureteral injury because of the rising popularity of operative laparoscopy. Lower urinary tract injury is certainly more common with laparoscopic hysterectomy than with abdominal or vaginal hysterectomy.

Increase has no single cause

BENT: There may be a small increase overall in lower urinary tract injury during pelvic surgery, since we now do more procedures that require complicated vaginal dissection and exploration of tissue planes in close proximity to the ureters. This has increased the rate of ureteral injuries.

There also have been a few more urethral injuries, again related to tension-free suburethral slings, most often involving the transobturator approach.

KARRAM: The higher rate of cesarean sections also plays a role. Many women undergoing hysterectomies have had 1 or more cesarean deliveries. We recently completed a study that shows that cesarean section is an independent risk factor for cystotomy at the time of hysterectomy.²

Unfortunately, many surgeons still use aggressive blunt dissection when they attempt to mobilize the bladder off the uterus—whether a hysterectomy is being performed abdominally or vaginally. This can lead to inadvertent entry into the bladder. For this reason, sharp dissection should always be used.

CUNDIFF: Based on my reading of the literature, the incidence of operative injury to the lower urinary tract during gynecologic surgery in general has not changed noticeably since Samson reviewed the subject in 1902³—although gynecologic surgery is the leading cause of such injuries and the leading cause of litigation against gynecologists.⁴

Most injuries involve hysterectomy

CUNDIFF: Most injuries occur during straightforward hysterectomies. Estimates of the prevalence of ureteral injury range from 0.4% to 2.4%.^5-8 Since most studies estimating prevalence have not evaluated the lower urinary tract in the whole study population, they may underestimate true prevalence. However, a recent study by Vakili and colleagues⁹ included universal endoscopy of all patients undergoing hysterectomy and reported rates of ureteral injury (1.7%) and bladder injury (3.6%) similar to those of less rigorous studies.

 

Overall, the incidence of lower urinary tract injury during other types of urogynecologic surgery is higher than during hysterectomy. Evidence of the higher prevalence during urogynecologic surgery comes from several recent studies. Harris et al¹⁰ reported a 5.7% injury rate during reconstructive surgery for incontinence or prolapse. Importantly, 4% were unrecognized prior to urinary tract endoscopy.

Procedures most commonly associated with urinary tract injury were retropubic urethropexy and apical prolapse procedures using the uterosacral ligament in this series. This higher prevalence in urogynecologic procedures may explain the perceived increase in injuries overall.

How can a surgeon prevent bladder or ureteral injury during open hysterectomy?

BENT: Any procedure—regardless of the approach—demands careful dissection, good lighting, and exposure of appropriate structures. It is hard to avoid what you cannot see!

CUNDIFF: When I enter the peritoneal cavity, especially in patients undergoing reoperation, I make the incision more superiorly and avoid the bladder when extending the incision inferiorly. I always open the pararectal space and identify the ureters to ensure their safety during clamping.

Dissection of the vesicovaginal space is most effective when it is done sharply with adequate traction and countertraction. This can be achieved by gently pulling the bladder anteriorly with a Babcock clamp, using scissors to dissect close to the cervix.

For very large fundi, dissection of the vesicovaginal space can be difficult if the uterus is brought through the laparotomy. In these cases I generally take the round ligaments and infundibulopelvic ligaments first and then push the fundus into the upper abdomen. This helps keep the bowel out of the field and gives better visualization of the vesicovaginal space.

I generally enter the anterior fornix with a scalpel and then use Jorgensen scissors to excise the cervix. This helps protect the bladder, and also maximizes vaginal length.

By the way, I use a modified lithotomy position with universal stirrups to maintain access to the bladder for cystoscopy, in case it is needed later.

Follow the ureter

BARBER: During abdominal hysterectomy, I routinely identify the course of the ureter in the retroperitoneum and follow it from where it enters the pelvis until it disappears into the cardinal ligament and below the uterine artery. Following its course helps me avoid ureteral injury.

BENT: If there is scarring of the tube or ovary, or a mass is present, the ureter may have to be localized and dissected completely free of the adnexal structures before any clamps are placed. In addition, the bladder flap should routinely be mobilized using sharp dissection, never blunt dissection.

Mobilization of the bladder downward also pushes the ureters further out of the way during clamping of the uterine vessels. If bleeding occurs, secure hemostasis after observing the location of the ureters. If there is any concern about injury, cystoscopy with injected dye is required.

Next, as the uterosacral and cardinal ligaments are approached, the bladder must be reflected well inferior to this area. This will keep the ureters somewhat removed from the clamps.

Other tricks include performing intrafascial hysterectomy, in which the fascia is peeled away from the uterus and cervix, protecting the ureters.

Clamps placed across the cardinal and uterosacral ligament complexes must hug the uterus and roll off the cervix to protect the ureter.

When the cuff is sutured after removal of the uterus, clear planes of vagina must be seen anteriorly and posteriorly to avoid suturing the bladder into the vaginal cuff.

3 preventive strategies

KARRAM: For abdominal hysterectomy, I recommend 3 techniques:

• Skeletonize the infundibulopelvic ligament. Most surgeons do this routinely during the abdominal approach; I also recommend it for laparoscopic hysterectomy. Once there is a window in the broad ligament and the infundibulopelvic ligament is skeletonized, one can be sure the ureter is well below this area and probably out of harm’s way.
• Use sharp dissection to mobilize the bladder off the anterior cervix.
• Maintain awareness of the close proximity of the lower ureter to the uterosacral cardinal ligament. As the ureter enters the bladder, it can be as close as 1 cm lateral to the uterosacral ligament. This is an area where it is almost impossible to dissect out the ureter, so the surgeon needs to appreciate this anatomy and refrain from taking aggressive bites in the lateral direction when supporting or closing the vaginal cuff.

How can a surgeon prevent bladder or ureteral injury during laparoscopic hysterectomy?

BARBER: I think the ureter is best identified by direct visualization transperitoneally. The angle of the laparoscope makes visualizing the ureter much easier than from an abdominal approach, so retroperitoneal dissection is not necessary as often.

 

If the course of the ureter is not readily identified by direct transperitoneal visualization, a peritoneal incision can be made below and parallel to the infundibulopelvic ligament, which allows entry into the retroperitoneum and, typically, easy visualization of the ureter throughout its course.

Alternatively, the retroperitoneum can be entered lateral to the infundibulopelvic ligament, and the ureter can be identified in the same manner as in abdominal hysterectomy.

If laparoscopically assisted hysterectomy is planned, I prefer to dissect the bladder flap vaginally rather than laparoscopically, as the risk of bladder injury is considerably lower from a vaginal approach than it is laparoscopically. Obviously, if a total laparoscopic hysterectomy is necessary because of poor vaginal access, laparoscopic bladder flap dissection is necessary. In this case, I again favor sharp dissection and minimal use of cautery to avoid bladder injury.

How can a surgeon prevent bladder or ureteral injury during vaginal hysterectomy?

BENT: Traditional methods in which each clamp is rolled off the cervix or uterus until the procedure is completed help keep unsuspecting surgeons out of the bladder and away from the ureter. The only risk involves bladder mobilization (ie, creation of the bladder flap), which should always be done sharply to prevent bladder perforation. Avoid blunt finger or sponge-stick dissection! Knowing how to sharply dissect the bladder flap is vital—then even cases of prior cesarean section are manageable.

Salpingo-oophorectomy can also proceed under direct vision. Avoid the ureter by making sure the clamp closes only over the pedicles of the tube and ovary, with no intervening tissues in the clamp. If space is very tight, divide the round ligament and take the pedicle in a smaller bite. Traction on the cervix during the procedure, and mobilization of the bladder, allow the ureters to slide upward, well out of harm’s way, as the procedure progresses.

The importance of sharp dissection

BARBER: During vaginal hysterectomy, I usually have the operative assistant hold the cervical tenaculum so that there is tension on the uterus. I then use forceps to elevate the bladder directly vertically in order to place the bladder fibers on tension. Next, I dissect the bladder off the cervix and lower uterine segment using sharp dissection, and identify the peritoneum by direct finger palpation. Almost always, it is smooth and slippery.

After identifying the peritoneum, I grasp it with a tonsil clamp and elevate it so that it can be entered easily with scissors. I always confirm peritoneal entry by visualizing and identifying intraperitoneal structures such as bowel fat, the uterine serosal surface, or adnexae.

Some people advocate palpating the ureter during vaginal cases.

CUNDIFF: The most common time of injury during vaginal hysterectomy is during dissection of the vesicovaginal space; and suture ligation of the infundibulopelvic ligaments and uterine arteries carries the greatest potential for ureteral injury.

During vaginal hysterectomy, I try to dissect the vesicovaginal space early. I use a Deever retractor to retract the bladder anteriorly, maximizing my ability to sharply dissect close to the cervix until entering the peritoneal cavity. Once I’m in the peritoneal cavity, I advance the Deever retractor to protect the bladder through the rest of the procedure. I maximize protection of the ureters by applying downward traction on the cervix during vaginal clamp placement.

KARRAM: I agree. Never try to enter the anterior cul-de-sac until the vesicouterine space has been identified and is easily palpated. Rushing to enter the anterior cul-de-sac will only lead to inadvertent cystotomy.

Assessing ureteral patency

After what pelvic surgeries do you think ureteral patency should be assessed, and how should it be accomplished?

CUNDIFF: The literature contains several studies^10-13 that involved universal endoscopy of the lower urinary tract. These studies demonstrate that most injuries are not recognized by the surgeon prior to endoscopy. In fact, the vast majority of injuries occur after straightforward hysterectomies. This may be due in part to the sheer volume of hysterectomies, compared with other pelvic surgeries. However, it also shows that, when lower urinary tract evaluation is performed solely when the surgeon suspects an injury, a substantial proportion of injuries are missed.

KARRAM: When do you assess ureteral patency?

CUNDIFF: My personal practice is to evaluate it in all cases that carry the potential for injury to the ureter. The complexity of the evaluation is proportional to the probability of ureteral injury.

For all laparotomies and laparoscopies, I identify the course of the ureter and confirm peristalsis. In the simplest of cases, this can be done by identifying the ureter beneath the peritoneum as it crosses the pelvic brim and courses across the pelvic sidewall. More frequently, it involves opening the pararectal space to identify the course of the ureter. In the most complex cases, it requires ureterolysis.

 

I strongly believe that identifying the ureter during any dissection that endangers it is the best way to avoid injury. Even after these precautions, I frequently perform cystoscopy with intravenous indigo carmine to confirm ureteral patency. This is my standard approach with all vaginal procedures, as I am not confident that I can palpate the course of the ureter.

Postoperative cystoscopy is virtually without morbidity and adds no more than 3 minutes to the procedure when properly planned. It also affords an excellent opportunity to train residents in cystoscopy.

How to assess patency after selected procedures

BENT: Ureteral patency should be assured after any repair of the pelvic floor.

After abdominal hysterectomy, if there is blood in the catheter bag or any difficulty has been encountered during surgery, I perform cystoscopy after injecting indigo carmine dye, to observe ureteral function.

At abdominal or laparoscopic sacrocolpopexy, I follow the path of the ureters over the pelvic brim and inferiorly to the adnexal area by direct inspection.

During abdominal or laparoscopic paravaginal repair, the Burch procedure, or uterosacral ligament suspension, I perform cystoscopy after tying sutures and injecting indigo carmine to ensure ureteral function.

To safeguard the ureter, follow its course

Vaginal hysterectomy is not usually associated with ureteral injury, and very uncommonly with bladder injury. However, if bladder injury is observed or the procedure has been difficult, it is wise to perform cystoscopy with dye injection. This also extends to traditional cystocele repair.

I also recommend cystoscopy with dye injection any time there is a vaginal approach to paravaginal defect repair, vault suspension, or colpocleisis.

Cystoscopy—safe, simple, and efficient

KARRAM: For vaginal surgery, I think cystoscopy is the simplest way to assess the lower urinary tract. I routinely use it after any procedures involving the posterior cul-de-sac such as McCall culdoplasty or vaginal vault suspension from the uterosacral ligaments. I also use it routinely after advanced prolapse repairs involving anterior colporrhaphy, as well as paravaginal defect repairs, and I certainly use it routinely after any lower urinary tract reconstructive procedures such as fistula repairs.

As for laparoscopic surgery, I think cystoscopy is again the most efficient way to assess the lower urinary tract. I do so after any retropubic suspension, be it a Burch colposuspension or a paravaginal repair, any type of vault suspension or sacrocolpopexy, and any type of hysterectomy or adnexectomy that involves dissection of the retroperitoneal space. I also do so if an energy source was used extensively in the vicinity of the retroperitoneal space on either side.

After abdominal surgery, it is probably more efficient (assuming the patient is not in stirrups) to perform a high extraperitoneal cystotomy or suprapubic telescopy. The indications are any difficult dissection in which I have concerns about ureteral patency, as well as any abdominal prolapse or anti-incontinence procedures.

Ureteral stenting

Is ureteral stenting ever indicated preoperatively? If so, when?

BARBER: I do not think ureteral stenting is indicated routinely for any procedure. There may be individual cases where a stent may help the surgeon avoid ureteral injury, but I can’t think of a procedure in which it should be routinely used.

CUNDIFF: I agree. Although ureteral stenting is an important tool for the pelvic floor surgeon to investigate potential ureteral obstruction, I think it has very limited value as a preoperative maneuver to avoid injury. My opinion is based on the following observations:

The surgeon cannot really assess the potential difficulty of identifying the course of the ureter until the peritoneal cavity is entered.

For the truly hostile pelvis, in which pelvic sidewall pathology prevents identification of the course of the ureter, I do not find that a stent facilitates dissection of the pararectal space and ureterolysis. In fact, it could increase the chance of ureteral injury by creating a backboard against which to cut it during dissection.

Any potential benefit of ureteral stents—which I believe is minimal—must be balanced against the potential risks, which include 20 to 30 minutes of added OR time and the risk of ureteral spasm or perforation.

BENT: I also agree that ureteral stenting is seldom helpful during gynecologic surgery. At laparotomy, direct dissection of the structures and exposure of the ureter are best; there is no need to feel for a ureter.

At laparoscopy, however, if there are large fibroids, scarring from endometriomas, or adnexal masses, then preoperative placement of lighted stents can help the surgeon identify the ureters during dissection. The case would still require dissection of the ureter away from the operative field, but the lighted path provides a starting point in this procedure.

 

For vaginal surgical procedures, it is easier to avoid the ureter. However, not all surgeons can palpate a nonstented ureter, which may be required during a high uterosacral ligament suspension. A stent can readily take the surgeon to the ureter and avoid injury in most cases. This may be helpful for less experienced operators.

What should residents be trained to do?

Do most obstetrics and gynecology residency programs appropriately train young physicians to evaluate and manage lower urinary tract injury during pelvic surgery?

CUNDIFF: I am afraid not. Although residency directors increasingly recognize the importance of educating doctors to prevent and manage these injuries, this recognition has not yet risen to the policy level.

For example, the Council on Resident Education in Obstetrics and Gynecology (CREOG) includes a bladder surgery educational model that necessitates dissection of the ureter, cystoscopy, ureteral stenting, bladder repair, and ureteral reanastomosis.

However, the CREOG surgical curriculum makes no mention of protecting or evaluating the lower urinary tract during pelvic surgery.

This spectrum seems to reflect the wide variation among residency programs, too. While some programs such as ours at Johns Hopkins provide comprehensive training in prevention, evaluation, and management of lower urinary tract injury, many others do not. This might be because some programs lack technically skilled faculty. Interdisciplinary politics also likely influences local credentialing.

BARBER: In my opinion, a graduating ObGyn resident should be able to:

• identify and mobilize the ureter to avoid injury during abdominal and laparoscopic surgery
• safely mobilize the bladder during abdominal, vaginal, or laparoscopic hysterectomy
• perform intraoperative cystoscopy to evaluate for injury
• repair bladder injuries abdominally and vaginally

However, I don’t think it is realistic for a graduating resident to be able to manage ureteral injuries, as residents are unlikely to encounter very many during training. These injuries are best left to our urology colleagues.

BENT: Very little or no education is provided in preventing lower urinary tract injury; evaluation is better managed in many programs. A conservative estimate is that 20% of programs have a reasonable curriculum for preoperative assessment and evaluation of incontinence and prolapse.

The management of pelvic floor disorders is better handled in almost all programs, especially as it relates to surgery. Many residents spend a lot of time on the urogynecology service and are exposed to the surgical aspect of rotations.

Dr. Karram and Dr. Barber have no financial relationships relevant to this article. Dr. Bent serves on the gynecology advisory board of ACMI and is a speaker for Novartis, Pfizer, Watson, and Asetellas (formerly Yamanouchi). He also has received research funding from Cook, Eli Lilly, and Mentor; and is a consultant for C.R. Bard. Dr. Cundiff has received grant/research support from Cook, is a consultant to C.R. Bard and Eli Lilly, and is a speaker for GlaxoSmithKline.

Unfortunate but true: Many complications of pelvic surgery involve injury to the lower urinary tract—and many of these injuries go undetected and increase the patient’s risk of serious morbidity and the physician’s chances of being sued.

Even more unfortunate: These injuries are on the rise, thanks to the proliferation of anti-incontinence surgeries, greater use of laparoscopy, and the need for increasingly complex vaginal dissection.

Fortunately, most lower urinary tract injuries can be avoided, or at least detected early, and this discussion centers on techniques to accomplish those goals and ensure bladder integrity and ureteral patency.

The rising injury rate

There appear to be more injuries to the lower urinary tract arising from pelvic surgery. Why do you think that is?

BARBER: I think the increase is due to the increasing popularity of midurethral slings, such as the tension-free vaginal tape (TVT). With these blind retropubic procedures, the risk of bladder injury is approximately 5%, which is considerably higher than in most other procedures we perform.¹

Fortunately, the negative consequences of placing the TVT trocar into the dome of the bladder are minimal, since the trocar can be removed and placed in the appropriate location without the need for bladder repair and without causing long-term bladder dysfunction.

KARRAM: The higher rate of injury also may be linked, in part, to greater use of energy sources during laparoscopic surgery. Over the past 2 years, we have seen numerous cases of delayed injury to the lower urinary tract or bowel secondary to thermal damage from energy devices including electrosurgical instruments and ultrasonic shears.

BARBER: I think there is an increase in lower urinary tract and ureteral injury because of the rising popularity of operative laparoscopy. Lower urinary tract injury is certainly more common with laparoscopic hysterectomy than with abdominal or vaginal hysterectomy.

Increase has no single cause

BENT: There may be a small increase overall in lower urinary tract injury during pelvic surgery, since we now do more procedures that require complicated vaginal dissection and exploration of tissue planes in close proximity to the ureters. This has increased the rate of ureteral injuries.

There also have been a few more urethral injuries, again related to tension-free suburethral slings, most often involving the transobturator approach.

KARRAM: The higher rate of cesarean sections also plays a role. Many women undergoing hysterectomies have had 1 or more cesarean deliveries. We recently completed a study that shows that cesarean section is an independent risk factor for cystotomy at the time of hysterectomy.²

Unfortunately, many surgeons still use aggressive blunt dissection when they attempt to mobilize the bladder off the uterus—whether a hysterectomy is being performed abdominally or vaginally. This can lead to inadvertent entry into the bladder. For this reason, sharp dissection should always be used.

CUNDIFF: Based on my reading of the literature, the incidence of operative injury to the lower urinary tract during gynecologic surgery in general has not changed noticeably since Samson reviewed the subject in 1902³—although gynecologic surgery is the leading cause of such injuries and the leading cause of litigation against gynecologists.⁴

Most injuries involve hysterectomy

CUNDIFF: Most injuries occur during straightforward hysterectomies. Estimates of the prevalence of ureteral injury range from 0.4% to 2.4%.^5-8 Since most studies estimating prevalence have not evaluated the lower urinary tract in the whole study population, they may underestimate true prevalence. However, a recent study by Vakili and colleagues⁹ included universal endoscopy of all patients undergoing hysterectomy and reported rates of ureteral injury (1.7%) and bladder injury (3.6%) similar to those of less rigorous studies.

 

Overall, the incidence of lower urinary tract injury during other types of urogynecologic surgery is higher than during hysterectomy. Evidence of the higher prevalence during urogynecologic surgery comes from several recent studies. Harris et al¹⁰ reported a 5.7% injury rate during reconstructive surgery for incontinence or prolapse. Importantly, 4% were unrecognized prior to urinary tract endoscopy.

Procedures most commonly associated with urinary tract injury were retropubic urethropexy and apical prolapse procedures using the uterosacral ligament in this series. This higher prevalence in urogynecologic procedures may explain the perceived increase in injuries overall.

How can a surgeon prevent bladder or ureteral injury during open hysterectomy?

BENT: Any procedure—regardless of the approach—demands careful dissection, good lighting, and exposure of appropriate structures. It is hard to avoid what you cannot see!

CUNDIFF: When I enter the peritoneal cavity, especially in patients undergoing reoperation, I make the incision more superiorly and avoid the bladder when extending the incision inferiorly. I always open the pararectal space and identify the ureters to ensure their safety during clamping.

Dissection of the vesicovaginal space is most effective when it is done sharply with adequate traction and countertraction. This can be achieved by gently pulling the bladder anteriorly with a Babcock clamp, using scissors to dissect close to the cervix.

For very large fundi, dissection of the vesicovaginal space can be difficult if the uterus is brought through the laparotomy. In these cases I generally take the round ligaments and infundibulopelvic ligaments first and then push the fundus into the upper abdomen. This helps keep the bowel out of the field and gives better visualization of the vesicovaginal space.

I generally enter the anterior fornix with a scalpel and then use Jorgensen scissors to excise the cervix. This helps protect the bladder, and also maximizes vaginal length.

By the way, I use a modified lithotomy position with universal stirrups to maintain access to the bladder for cystoscopy, in case it is needed later.

Follow the ureter

BARBER: During abdominal hysterectomy, I routinely identify the course of the ureter in the retroperitoneum and follow it from where it enters the pelvis until it disappears into the cardinal ligament and below the uterine artery. Following its course helps me avoid ureteral injury.

BENT: If there is scarring of the tube or ovary, or a mass is present, the ureter may have to be localized and dissected completely free of the adnexal structures before any clamps are placed. In addition, the bladder flap should routinely be mobilized using sharp dissection, never blunt dissection.

Mobilization of the bladder downward also pushes the ureters further out of the way during clamping of the uterine vessels. If bleeding occurs, secure hemostasis after observing the location of the ureters. If there is any concern about injury, cystoscopy with injected dye is required.

Next, as the uterosacral and cardinal ligaments are approached, the bladder must be reflected well inferior to this area. This will keep the ureters somewhat removed from the clamps.

Other tricks include performing intrafascial hysterectomy, in which the fascia is peeled away from the uterus and cervix, protecting the ureters.

Clamps placed across the cardinal and uterosacral ligament complexes must hug the uterus and roll off the cervix to protect the ureter.

When the cuff is sutured after removal of the uterus, clear planes of vagina must be seen anteriorly and posteriorly to avoid suturing the bladder into the vaginal cuff.

3 preventive strategies

KARRAM: For abdominal hysterectomy, I recommend 3 techniques:

• Skeletonize the infundibulopelvic ligament. Most surgeons do this routinely during the abdominal approach; I also recommend it for laparoscopic hysterectomy. Once there is a window in the broad ligament and the infundibulopelvic ligament is skeletonized, one can be sure the ureter is well below this area and probably out of harm’s way.
• Use sharp dissection to mobilize the bladder off the anterior cervix.
• Maintain awareness of the close proximity of the lower ureter to the uterosacral cardinal ligament. As the ureter enters the bladder, it can be as close as 1 cm lateral to the uterosacral ligament. This is an area where it is almost impossible to dissect out the ureter, so the surgeon needs to appreciate this anatomy and refrain from taking aggressive bites in the lateral direction when supporting or closing the vaginal cuff.

How can a surgeon prevent bladder or ureteral injury during laparoscopic hysterectomy?

BARBER: I think the ureter is best identified by direct visualization transperitoneally. The angle of the laparoscope makes visualizing the ureter much easier than from an abdominal approach, so retroperitoneal dissection is not necessary as often.

 

If the course of the ureter is not readily identified by direct transperitoneal visualization, a peritoneal incision can be made below and parallel to the infundibulopelvic ligament, which allows entry into the retroperitoneum and, typically, easy visualization of the ureter throughout its course.

Alternatively, the retroperitoneum can be entered lateral to the infundibulopelvic ligament, and the ureter can be identified in the same manner as in abdominal hysterectomy.

If laparoscopically assisted hysterectomy is planned, I prefer to dissect the bladder flap vaginally rather than laparoscopically, as the risk of bladder injury is considerably lower from a vaginal approach than it is laparoscopically. Obviously, if a total laparoscopic hysterectomy is necessary because of poor vaginal access, laparoscopic bladder flap dissection is necessary. In this case, I again favor sharp dissection and minimal use of cautery to avoid bladder injury.

How can a surgeon prevent bladder or ureteral injury during vaginal hysterectomy?

BENT: Traditional methods in which each clamp is rolled off the cervix or uterus until the procedure is completed help keep unsuspecting surgeons out of the bladder and away from the ureter. The only risk involves bladder mobilization (ie, creation of the bladder flap), which should always be done sharply to prevent bladder perforation. Avoid blunt finger or sponge-stick dissection! Knowing how to sharply dissect the bladder flap is vital—then even cases of prior cesarean section are manageable.

Salpingo-oophorectomy can also proceed under direct vision. Avoid the ureter by making sure the clamp closes only over the pedicles of the tube and ovary, with no intervening tissues in the clamp. If space is very tight, divide the round ligament and take the pedicle in a smaller bite. Traction on the cervix during the procedure, and mobilization of the bladder, allow the ureters to slide upward, well out of harm’s way, as the procedure progresses.

The importance of sharp dissection

BARBER: During vaginal hysterectomy, I usually have the operative assistant hold the cervical tenaculum so that there is tension on the uterus. I then use forceps to elevate the bladder directly vertically in order to place the bladder fibers on tension. Next, I dissect the bladder off the cervix and lower uterine segment using sharp dissection, and identify the peritoneum by direct finger palpation. Almost always, it is smooth and slippery.

After identifying the peritoneum, I grasp it with a tonsil clamp and elevate it so that it can be entered easily with scissors. I always confirm peritoneal entry by visualizing and identifying intraperitoneal structures such as bowel fat, the uterine serosal surface, or adnexae.

Some people advocate palpating the ureter during vaginal cases.

CUNDIFF: The most common time of injury during vaginal hysterectomy is during dissection of the vesicovaginal space; and suture ligation of the infundibulopelvic ligaments and uterine arteries carries the greatest potential for ureteral injury.

During vaginal hysterectomy, I try to dissect the vesicovaginal space early. I use a Deever retractor to retract the bladder anteriorly, maximizing my ability to sharply dissect close to the cervix until entering the peritoneal cavity. Once I’m in the peritoneal cavity, I advance the Deever retractor to protect the bladder through the rest of the procedure. I maximize protection of the ureters by applying downward traction on the cervix during vaginal clamp placement.

KARRAM: I agree. Never try to enter the anterior cul-de-sac until the vesicouterine space has been identified and is easily palpated. Rushing to enter the anterior cul-de-sac will only lead to inadvertent cystotomy.

Assessing ureteral patency

After what pelvic surgeries do you think ureteral patency should be assessed, and how should it be accomplished?

CUNDIFF: The literature contains several studies^10-13 that involved universal endoscopy of the lower urinary tract. These studies demonstrate that most injuries are not recognized by the surgeon prior to endoscopy. In fact, the vast majority of injuries occur after straightforward hysterectomies. This may be due in part to the sheer volume of hysterectomies, compared with other pelvic surgeries. However, it also shows that, when lower urinary tract evaluation is performed solely when the surgeon suspects an injury, a substantial proportion of injuries are missed.

KARRAM: When do you assess ureteral patency?

CUNDIFF: My personal practice is to evaluate it in all cases that carry the potential for injury to the ureter. The complexity of the evaluation is proportional to the probability of ureteral injury.

For all laparotomies and laparoscopies, I identify the course of the ureter and confirm peristalsis. In the simplest of cases, this can be done by identifying the ureter beneath the peritoneum as it crosses the pelvic brim and courses across the pelvic sidewall. More frequently, it involves opening the pararectal space to identify the course of the ureter. In the most complex cases, it requires ureterolysis.

 

I strongly believe that identifying the ureter during any dissection that endangers it is the best way to avoid injury. Even after these precautions, I frequently perform cystoscopy with intravenous indigo carmine to confirm ureteral patency. This is my standard approach with all vaginal procedures, as I am not confident that I can palpate the course of the ureter.

Postoperative cystoscopy is virtually without morbidity and adds no more than 3 minutes to the procedure when properly planned. It also affords an excellent opportunity to train residents in cystoscopy.

How to assess patency after selected procedures

BENT: Ureteral patency should be assured after any repair of the pelvic floor.

After abdominal hysterectomy, if there is blood in the catheter bag or any difficulty has been encountered during surgery, I perform cystoscopy after injecting indigo carmine dye, to observe ureteral function.

At abdominal or laparoscopic sacrocolpopexy, I follow the path of the ureters over the pelvic brim and inferiorly to the adnexal area by direct inspection.

During abdominal or laparoscopic paravaginal repair, the Burch procedure, or uterosacral ligament suspension, I perform cystoscopy after tying sutures and injecting indigo carmine to ensure ureteral function.

To safeguard the ureter, follow its course

Vaginal hysterectomy is not usually associated with ureteral injury, and very uncommonly with bladder injury. However, if bladder injury is observed or the procedure has been difficult, it is wise to perform cystoscopy with dye injection. This also extends to traditional cystocele repair.

I also recommend cystoscopy with dye injection any time there is a vaginal approach to paravaginal defect repair, vault suspension, or colpocleisis.

Cystoscopy—safe, simple, and efficient

KARRAM: For vaginal surgery, I think cystoscopy is the simplest way to assess the lower urinary tract. I routinely use it after any procedures involving the posterior cul-de-sac such as McCall culdoplasty or vaginal vault suspension from the uterosacral ligaments. I also use it routinely after advanced prolapse repairs involving anterior colporrhaphy, as well as paravaginal defect repairs, and I certainly use it routinely after any lower urinary tract reconstructive procedures such as fistula repairs.

As for laparoscopic surgery, I think cystoscopy is again the most efficient way to assess the lower urinary tract. I do so after any retropubic suspension, be it a Burch colposuspension or a paravaginal repair, any type of vault suspension or sacrocolpopexy, and any type of hysterectomy or adnexectomy that involves dissection of the retroperitoneal space. I also do so if an energy source was used extensively in the vicinity of the retroperitoneal space on either side.

After abdominal surgery, it is probably more efficient (assuming the patient is not in stirrups) to perform a high extraperitoneal cystotomy or suprapubic telescopy. The indications are any difficult dissection in which I have concerns about ureteral patency, as well as any abdominal prolapse or anti-incontinence procedures.

Ureteral stenting

Is ureteral stenting ever indicated preoperatively? If so, when?

BARBER: I do not think ureteral stenting is indicated routinely for any procedure. There may be individual cases where a stent may help the surgeon avoid ureteral injury, but I can’t think of a procedure in which it should be routinely used.

CUNDIFF: I agree. Although ureteral stenting is an important tool for the pelvic floor surgeon to investigate potential ureteral obstruction, I think it has very limited value as a preoperative maneuver to avoid injury. My opinion is based on the following observations:

The surgeon cannot really assess the potential difficulty of identifying the course of the ureter until the peritoneal cavity is entered.

For the truly hostile pelvis, in which pelvic sidewall pathology prevents identification of the course of the ureter, I do not find that a stent facilitates dissection of the pararectal space and ureterolysis. In fact, it could increase the chance of ureteral injury by creating a backboard against which to cut it during dissection.

Any potential benefit of ureteral stents—which I believe is minimal—must be balanced against the potential risks, which include 20 to 30 minutes of added OR time and the risk of ureteral spasm or perforation.

BENT: I also agree that ureteral stenting is seldom helpful during gynecologic surgery. At laparotomy, direct dissection of the structures and exposure of the ureter are best; there is no need to feel for a ureter.

At laparoscopy, however, if there are large fibroids, scarring from endometriomas, or adnexal masses, then preoperative placement of lighted stents can help the surgeon identify the ureters during dissection. The case would still require dissection of the ureter away from the operative field, but the lighted path provides a starting point in this procedure.

 

For vaginal surgical procedures, it is easier to avoid the ureter. However, not all surgeons can palpate a nonstented ureter, which may be required during a high uterosacral ligament suspension. A stent can readily take the surgeon to the ureter and avoid injury in most cases. This may be helpful for less experienced operators.

What should residents be trained to do?

Do most obstetrics and gynecology residency programs appropriately train young physicians to evaluate and manage lower urinary tract injury during pelvic surgery?

CUNDIFF: I am afraid not. Although residency directors increasingly recognize the importance of educating doctors to prevent and manage these injuries, this recognition has not yet risen to the policy level.

For example, the Council on Resident Education in Obstetrics and Gynecology (CREOG) includes a bladder surgery educational model that necessitates dissection of the ureter, cystoscopy, ureteral stenting, bladder repair, and ureteral reanastomosis.

However, the CREOG surgical curriculum makes no mention of protecting or evaluating the lower urinary tract during pelvic surgery.

This spectrum seems to reflect the wide variation among residency programs, too. While some programs such as ours at Johns Hopkins provide comprehensive training in prevention, evaluation, and management of lower urinary tract injury, many others do not. This might be because some programs lack technically skilled faculty. Interdisciplinary politics also likely influences local credentialing.

BARBER: In my opinion, a graduating ObGyn resident should be able to:

• identify and mobilize the ureter to avoid injury during abdominal and laparoscopic surgery
• safely mobilize the bladder during abdominal, vaginal, or laparoscopic hysterectomy
• perform intraoperative cystoscopy to evaluate for injury
• repair bladder injuries abdominally and vaginally

However, I don’t think it is realistic for a graduating resident to be able to manage ureteral injuries, as residents are unlikely to encounter very many during training. These injuries are best left to our urology colleagues.

BENT: Very little or no education is provided in preventing lower urinary tract injury; evaluation is better managed in many programs. A conservative estimate is that 20% of programs have a reasonable curriculum for preoperative assessment and evaluation of incontinence and prolapse.

The management of pelvic floor disorders is better handled in almost all programs, especially as it relates to surgery. Many residents spend a lot of time on the urogynecology service and are exposed to the surgical aspect of rotations.

Dr. Karram and Dr. Barber have no financial relationships relevant to this article. Dr. Bent serves on the gynecology advisory board of ACMI and is a speaker for Novartis, Pfizer, Watson, and Asetellas (formerly Yamanouchi). He also has received research funding from Cook, Eli Lilly, and Mentor; and is a consultant for C.R. Bard. Dr. Cundiff has received grant/research support from Cook, is a consultant to C.R. Bard and Eli Lilly, and is a speaker for GlaxoSmithKline.

Of 72 different ways to prevent surgical site infections, 49 are backed by enough confirmatory science to merit the CDC’s strongest recommendation for use in all hospitals. (The 23 other measures in the CDC advisory have not been or cannot be as thoroughly studied.)

How can we apply all possible precautions to every patient wheeled into the OR? The CDC’s Guideline for Prevention of Surgical Site Infections (formerly termed wound infections) advocates “a systematic but realistic approach” based on the evidence, coupled with awareness that risk of surgical site infection is influenced by characteristics of the patient, operation, personnel, and hospital.

This article reviews key evidence behind a number of the most strongly recommended measures, such as optimal regimens for prophylactic antibiotics, and some of the recommendations for which equally rigorous evidence is lacking.

The CDC’s Guideline ranks its recommendations according to 4 levels of evidence. A total of 49 recommendations meet the most rigorous evidence standards, and therefore are “strongly recommended for all hospitals.” (See How strong is the evidence?.)

Many of our infection prevention routines, of course, have been standard ever since Joseph Lister introduced the principles of antisepsis in the late 1860s. Technically, however, some standard infection prevention routines are based on a strong theoretical rationale along with suggestive though not confirmatory science.

By necessity, narrowly defined patient populations and ethical and logistical issues will always limit our ability to obtain confirmatory scientific answers to some questions. For example, wearing gloves vs not wearing gloves fits into that category. Likewise, the evidence on preoperative nutritional support for the sole purpose of preventing SSI does not meet the criteria for the best evidence category, “1A.” Yet, nutrition therapy is among the CDC’s recommendations, albeit the evidence behind it falls into the “NR” category, “no recommendation; unresolved issue.”

The CDC’s exhaustive guideline identifies 21 characteristics of patients and operations that influence a patient’s risk of surgical site infection (TABLE 1), and recommends prevention tactics that are backed by evidence (See CDC Advisory).

The CDC’s recommendations are grouped into these sections:

1. Preoperative preparation of the patient, hand/forearm antisepsis for surgical team members, management of infected or colonized surgical personnel, and antimicrobial prophylaxis.

2. Intraoperative ventilation, cleaning and disinfection of environmental surfaces, microbiologic sampling, sterilization of surgical instruments, surgical attire and drapes, asepsis, and surgical technique.

3. Postoperative incision care.

4. Surveillance.

TABLE 1

21 factors that influence risk of surgical site infection

PATIENT
1 Age
2 Nutritional status
3 Diabetes
4 Smoking
5 Obesity
6 Coexistent infections at remote body site
7 Colonization with microorganisms
8 Altered immune response
9 Length of preoperative stay
OPERATION
10 Duration of surgical scrub
11 Skin antisepsis
12 Preoperative shaving
13 Duration of operation
14 Antimicrobial prophylaxis
15 Operating room ventilation
16 Inadequate sterilization of instruments
17 Foreign material in the surgical site
18 Surgical drains
19 Poor hemostasis
20 Failure to obliterate dead space
21 Tissue trauma
Source: Reference 1.

Preparing The Patient

Preoperative risk factors

Infection prevention begins with considering the preoperative risk factors of the patient’s condition.

Not all risk factors for surgical site infections can be modified (age, for example), but we should correct whatever we can before scheduling elective surgery.

Minimizing smoking improves postoperative SSI outcomes(EVIDENCE CATEGORY IB).

Weight loss before surgery has not been clearly correlated with improved SSI outcomes (EVIDENCE CATEGORY NR). However, body mass index may influence surgical complication rates, perhaps acting as a surrogate for technical difficulty or impaired wound-healing capacity.^2,3

Nutritionis being recognized as a key determinant in outcomes, but reports have not established how preoperative parenteral or enteral nutrition influences SSI outcome (NO RECOMMENDATION).^4,5

Antisepsis in the surgical field

The microbial source for most SSI is the patient’s endogenous flora, and the operative field determines the type of flora that will be encountered.

Normal skin flora consist mostly of gram-positive aerobes.

Antiseptic showering before surgery significantly reduces resident skin flora (EVIDENCE CATEGORY IB). Multiple showers with chlorhexidine have been shown to reduce resident bacteria up to 9-fold, but whether that reduces SSI rates is unclear.⁶

Prophylactic eradication of nasal Staph colonization (NO RECOMMENDATION). Recent attention has focused on microbial colonization with resistant organisms—and Staphylococcus aureus colonization of nares in cardiac surgery patients was found to be a major independent risk factor for surgical site infection.

 

Prophylactic intranasal mupirocin reduced infection risk in cardiothoracic patients,⁷ but preoperative use did not reduce gram-positive SSI rates in digestive tract surgery.⁸

Mupirocin also failed to reduce the wound rates in patients who had a variety of procedures, although the rate of nosocomial S aureus infections in the subset of patients with nasal colonization was reduced.⁹

Topical microbicides

Soap-and-water washing removes most debris from skin or other surgical surfaces, but antiseptic solutions reduce resident skin flora populations. The choice of appropriate topical microbicides during surgery can influence SSI rates (EVIDENCE CATEGORY IB).

When selecting an antiseptic, consider the anticipated duration of the case, the epithelial surface to be breeched (mucous membrane vs keratinized skin), and the anticipated flora.

Shaving and hair removal

Hair removal is often necessary, but shaving may cause skin trauma that exacerbates bacterial growth.¹⁰ SSI rates correlate with the time interval between shaving and incision (20% if shaved >24 hours before surgery, 7.1% the night before, and 3.1% in the OR).¹¹ Thus, the CDC guidelines discourage shaving prior to surgery (EVIDENCE CATEGORY IA).Patients have been known to shave the operative area themselves before surgery, so all patients must be told not to shave themselves before elective surgery.

When hair removal is necessary, preoperative clipping causes minimal skin trauma (EVIDENCE CATEGORY IA).

Preparing The Surgical Staff

The surgeon’s hands

Evidence has shown that 2 minutes of preoperative scrubbing reduces resident flora as effectively as scrubbing for 10 minutes.¹ The recommended scrub should include hands and forearms up to the elbows for 2 to 5 minutes (EVIDENCE CATEGORY IB).

Keep hands away from the body and dry hands with a sterile towel (EVIDENCE CATEGORY IB).

Keep fingernails short (EVIDENCE CATEGORY IB), and clean under each nail at the beginning of each day (EVIDENCE CATEGORY II).

An aqueous alcohol solution is a recent alternative to traditional hand antisepsis with chlorhexidine- or povoidoneiodine–based solutions. No difference in SSI rates has been documented between hand-rubbing with an aqueous alcohol solution and traditional scrubbing.¹² A traditional scrub before the first of consecutive cases and after contact with gross contamination is still in order.

Sterile barriers

Sterile barriers in the operating room, indispensable in protecting staff, are federally mandated. Their role in preventing SSI is not clear. Surprisingly, the use of face masks may not contribute to SSI reduction.¹³ Head covering, on the other hand, markedly reduces airborne and wound bacterial contamination.¹⁴

Optimize Wound Physiology

Maintaining normothermia

Hypothermia is common, particularly in patients who are immunocompromised, at age extremes, or have multiple trauma. Hypothermic vasoconstriction may reduce tissue perfusion and increase risk of infection.

A double-blind study showed that maintaining intraoperative normothermia decreased SSI in colorectal patients from 19% to 6%.¹⁵ Additionally, preoperative warming of the entire body or local site for 30 minutes reduced SSI rates in clean surgical cases.¹⁶

Wound space oxygenation

Supplemental oxygen in colorectal surgery may correlate with lower infection rates (80% without supplemental oxygen, 30% with).¹⁷ This may improve tissue oxygen tension, which enhances oxidative bactericidal capacity.

However, these findings were not duplicated in patients with higher SSI rates and on supplemental hyperoxia.¹⁸ There are no recommendations for enhancing wound space oxygenation.

Control of glycemia

Cardiothoracic surgery studies have stressed the importance of tight perioperative glycemic control. Coronary artery bypass patients with higher mean perioperative glucose showed a trend toward a higher risk of nosocomial infection, but not specifically SSI.¹⁹ Another study of cardiothoracic patients found an association between higher risk of SSI and both diabetes and postoperative hyperglycemia.²⁰ Continuous intravenous insulin to maintain a blood glucose 21

 

Remote infections

Remote infections at the time of surgery, such as urinary tract infection or pneumonia, significantly raise the risk of SSI (EVIDENCE CATEGORY IA).

Strongly consider canceling elective surgery if there is an untreated remote infection, especially if implanting bioprosthetic material.

Surgical technique

Careful technique reduces risk of infection.

Breaks in sterile technique and gross spillage of enteric contents raise the risk for SSI through increased bacterial load.

Poor hemostasis, excess tissue trauma, inadequate debridement or dead space obliteration, and inappropriate suture technique raise the volume of unperfused biological matter (EVIDENCE CATEGORY IB).

Timely completion of the operation also minimizes risk. Prolonged operative time can heighten the risk of breaches in sterile technique. Recommendations call for procedures to be completed within the 75th percentile of standardized operative times.

Antimicrobial prophylaxis

The principles for using preoperative antibiotics include maximal subcutaneous concentration when making the incision (TABLE 2) (EVIDENCE CATEGORY IA). This corresponds with intravenous antimicrobial administration within 60 minutes before incision (or within 120 minutes for vancomycin or fluoroquinolones). An additional dose of the antimicrobial agent is indicated if the procedure time exceeds 2 half-lives of the agent.

Institutional policies for antibiotic restriction aimed at curtailing resistant organisms do not appear to change the spectrum of causative microbes in SSI.²² Short-duration therapy preserves antimicrobial efficacy best, so avoid the routine use of agents such as vancomycin (EVIDENCE CATEGORY IB).

Short duration also applies when antimicrobial prophylaxis is indicated. The CDC recommends extending antimicrobial prophylaxis no more than a few hours after incision closure (EVIDENCE CATEGORY IA). Particular cases may require longer antimicrobial prophylaxis, but prophylaxis beyond 24 hours does not reduce SSI rates and increases the potential for microbial resistance.

While a single dose of broad-spectrum antibiotic may cause Clostridium difficile colitis, prolonged duration also raises risk through profound changes in gut flora that favor the emergence of this opportunistic pathogen.

TABLE 2

Principles of antimicrobial prophylaxis

Consider these factors:
Risk for developing surgical site infection.
Potential severity of consequences
Prosthetic implantation
Cardiothoracic or vascular surgery
Agents must be safe, inexpensive, and bactericidal
Appropriate spectrum based on anticipated flora of involved tissues and spaces
Administer so that maximal effect is at time of incision, and re-administer when appropriate
Alter dosage as appropriate for the patient (eg, obesity)

The authors report no financial relationships relevant to this article.

This article is adapted from DiRocco JD, Pavone LA, Weiss CA III. The evidence-based way to prevent SSI. Contemp Surg. 2005;61:120–127.

Of 72 different ways to prevent surgical site infections, 49 are backed by enough confirmatory science to merit the CDC’s strongest recommendation for use in all hospitals. (The 23 other measures in the CDC advisory have not been or cannot be as thoroughly studied.)

How can we apply all possible precautions to every patient wheeled into the OR? The CDC’s Guideline for Prevention of Surgical Site Infections (formerly termed wound infections) advocates “a systematic but realistic approach” based on the evidence, coupled with awareness that risk of surgical site infection is influenced by characteristics of the patient, operation, personnel, and hospital.

This article reviews key evidence behind a number of the most strongly recommended measures, such as optimal regimens for prophylactic antibiotics, and some of the recommendations for which equally rigorous evidence is lacking.

The CDC’s Guideline ranks its recommendations according to 4 levels of evidence. A total of 49 recommendations meet the most rigorous evidence standards, and therefore are “strongly recommended for all hospitals.” (See How strong is the evidence?.)

Many of our infection prevention routines, of course, have been standard ever since Joseph Lister introduced the principles of antisepsis in the late 1860s. Technically, however, some standard infection prevention routines are based on a strong theoretical rationale along with suggestive though not confirmatory science.

By necessity, narrowly defined patient populations and ethical and logistical issues will always limit our ability to obtain confirmatory scientific answers to some questions. For example, wearing gloves vs not wearing gloves fits into that category. Likewise, the evidence on preoperative nutritional support for the sole purpose of preventing SSI does not meet the criteria for the best evidence category, “1A.” Yet, nutrition therapy is among the CDC’s recommendations, albeit the evidence behind it falls into the “NR” category, “no recommendation; unresolved issue.”

The CDC’s exhaustive guideline identifies 21 characteristics of patients and operations that influence a patient’s risk of surgical site infection (TABLE 1), and recommends prevention tactics that are backed by evidence (See CDC Advisory).

The CDC’s recommendations are grouped into these sections:

1. Preoperative preparation of the patient, hand/forearm antisepsis for surgical team members, management of infected or colonized surgical personnel, and antimicrobial prophylaxis.

2. Intraoperative ventilation, cleaning and disinfection of environmental surfaces, microbiologic sampling, sterilization of surgical instruments, surgical attire and drapes, asepsis, and surgical technique.

3. Postoperative incision care.

4. Surveillance.

TABLE 1

21 factors that influence risk of surgical site infection

PATIENT
1 Age
2 Nutritional status
3 Diabetes
4 Smoking
5 Obesity
6 Coexistent infections at remote body site
7 Colonization with microorganisms
8 Altered immune response
9 Length of preoperative stay
OPERATION
10 Duration of surgical scrub
11 Skin antisepsis
12 Preoperative shaving
13 Duration of operation
14 Antimicrobial prophylaxis
15 Operating room ventilation
16 Inadequate sterilization of instruments
17 Foreign material in the surgical site
18 Surgical drains
19 Poor hemostasis
20 Failure to obliterate dead space
21 Tissue trauma
Source: Reference 1.

Preparing The Patient

Preoperative risk factors

Infection prevention begins with considering the preoperative risk factors of the patient’s condition.

Not all risk factors for surgical site infections can be modified (age, for example), but we should correct whatever we can before scheduling elective surgery.

Minimizing smoking improves postoperative SSI outcomes(EVIDENCE CATEGORY IB).

Weight loss before surgery has not been clearly correlated with improved SSI outcomes (EVIDENCE CATEGORY NR). However, body mass index may influence surgical complication rates, perhaps acting as a surrogate for technical difficulty or impaired wound-healing capacity.^2,3

Nutritionis being recognized as a key determinant in outcomes, but reports have not established how preoperative parenteral or enteral nutrition influences SSI outcome (NO RECOMMENDATION).^4,5

Antisepsis in the surgical field

The microbial source for most SSI is the patient’s endogenous flora, and the operative field determines the type of flora that will be encountered.

Normal skin flora consist mostly of gram-positive aerobes.

Antiseptic showering before surgery significantly reduces resident skin flora (EVIDENCE CATEGORY IB). Multiple showers with chlorhexidine have been shown to reduce resident bacteria up to 9-fold, but whether that reduces SSI rates is unclear.⁶

Prophylactic eradication of nasal Staph colonization (NO RECOMMENDATION). Recent attention has focused on microbial colonization with resistant organisms—and Staphylococcus aureus colonization of nares in cardiac surgery patients was found to be a major independent risk factor for surgical site infection.

 

Prophylactic intranasal mupirocin reduced infection risk in cardiothoracic patients,⁷ but preoperative use did not reduce gram-positive SSI rates in digestive tract surgery.⁸

Mupirocin also failed to reduce the wound rates in patients who had a variety of procedures, although the rate of nosocomial S aureus infections in the subset of patients with nasal colonization was reduced.⁹

Topical microbicides

Soap-and-water washing removes most debris from skin or other surgical surfaces, but antiseptic solutions reduce resident skin flora populations. The choice of appropriate topical microbicides during surgery can influence SSI rates (EVIDENCE CATEGORY IB).

When selecting an antiseptic, consider the anticipated duration of the case, the epithelial surface to be breeched (mucous membrane vs keratinized skin), and the anticipated flora.

Shaving and hair removal

Hair removal is often necessary, but shaving may cause skin trauma that exacerbates bacterial growth.¹⁰ SSI rates correlate with the time interval between shaving and incision (20% if shaved >24 hours before surgery, 7.1% the night before, and 3.1% in the OR).¹¹ Thus, the CDC guidelines discourage shaving prior to surgery (EVIDENCE CATEGORY IA).Patients have been known to shave the operative area themselves before surgery, so all patients must be told not to shave themselves before elective surgery.

When hair removal is necessary, preoperative clipping causes minimal skin trauma (EVIDENCE CATEGORY IA).

Preparing The Surgical Staff

The surgeon’s hands

Evidence has shown that 2 minutes of preoperative scrubbing reduces resident flora as effectively as scrubbing for 10 minutes.¹ The recommended scrub should include hands and forearms up to the elbows for 2 to 5 minutes (EVIDENCE CATEGORY IB).

Keep hands away from the body and dry hands with a sterile towel (EVIDENCE CATEGORY IB).

Keep fingernails short (EVIDENCE CATEGORY IB), and clean under each nail at the beginning of each day (EVIDENCE CATEGORY II).

An aqueous alcohol solution is a recent alternative to traditional hand antisepsis with chlorhexidine- or povoidoneiodine–based solutions. No difference in SSI rates has been documented between hand-rubbing with an aqueous alcohol solution and traditional scrubbing.¹² A traditional scrub before the first of consecutive cases and after contact with gross contamination is still in order.

Sterile barriers

Sterile barriers in the operating room, indispensable in protecting staff, are federally mandated. Their role in preventing SSI is not clear. Surprisingly, the use of face masks may not contribute to SSI reduction.¹³ Head covering, on the other hand, markedly reduces airborne and wound bacterial contamination.¹⁴

Optimize Wound Physiology

Maintaining normothermia

Hypothermia is common, particularly in patients who are immunocompromised, at age extremes, or have multiple trauma. Hypothermic vasoconstriction may reduce tissue perfusion and increase risk of infection.

A double-blind study showed that maintaining intraoperative normothermia decreased SSI in colorectal patients from 19% to 6%.¹⁵ Additionally, preoperative warming of the entire body or local site for 30 minutes reduced SSI rates in clean surgical cases.¹⁶

Wound space oxygenation

Supplemental oxygen in colorectal surgery may correlate with lower infection rates (80% without supplemental oxygen, 30% with).¹⁷ This may improve tissue oxygen tension, which enhances oxidative bactericidal capacity.

However, these findings were not duplicated in patients with higher SSI rates and on supplemental hyperoxia.¹⁸ There are no recommendations for enhancing wound space oxygenation.

Control of glycemia

Cardiothoracic surgery studies have stressed the importance of tight perioperative glycemic control. Coronary artery bypass patients with higher mean perioperative glucose showed a trend toward a higher risk of nosocomial infection, but not specifically SSI.¹⁹ Another study of cardiothoracic patients found an association between higher risk of SSI and both diabetes and postoperative hyperglycemia.²⁰ Continuous intravenous insulin to maintain a blood glucose 21

 

Remote infections

Remote infections at the time of surgery, such as urinary tract infection or pneumonia, significantly raise the risk of SSI (EVIDENCE CATEGORY IA).

Strongly consider canceling elective surgery if there is an untreated remote infection, especially if implanting bioprosthetic material.

Surgical technique

Careful technique reduces risk of infection.

Breaks in sterile technique and gross spillage of enteric contents raise the risk for SSI through increased bacterial load.

Poor hemostasis, excess tissue trauma, inadequate debridement or dead space obliteration, and inappropriate suture technique raise the volume of unperfused biological matter (EVIDENCE CATEGORY IB).

Timely completion of the operation also minimizes risk. Prolonged operative time can heighten the risk of breaches in sterile technique. Recommendations call for procedures to be completed within the 75th percentile of standardized operative times.

Antimicrobial prophylaxis

The principles for using preoperative antibiotics include maximal subcutaneous concentration when making the incision (TABLE 2) (EVIDENCE CATEGORY IA). This corresponds with intravenous antimicrobial administration within 60 minutes before incision (or within 120 minutes for vancomycin or fluoroquinolones). An additional dose of the antimicrobial agent is indicated if the procedure time exceeds 2 half-lives of the agent.

Institutional policies for antibiotic restriction aimed at curtailing resistant organisms do not appear to change the spectrum of causative microbes in SSI.²² Short-duration therapy preserves antimicrobial efficacy best, so avoid the routine use of agents such as vancomycin (EVIDENCE CATEGORY IB).

Short duration also applies when antimicrobial prophylaxis is indicated. The CDC recommends extending antimicrobial prophylaxis no more than a few hours after incision closure (EVIDENCE CATEGORY IA). Particular cases may require longer antimicrobial prophylaxis, but prophylaxis beyond 24 hours does not reduce SSI rates and increases the potential for microbial resistance.

While a single dose of broad-spectrum antibiotic may cause Clostridium difficile colitis, prolonged duration also raises risk through profound changes in gut flora that favor the emergence of this opportunistic pathogen.

TABLE 2

Principles of antimicrobial prophylaxis

Consider these factors:
Risk for developing surgical site infection.
Potential severity of consequences
Prosthetic implantation
Cardiothoracic or vascular surgery
Agents must be safe, inexpensive, and bactericidal
Appropriate spectrum based on anticipated flora of involved tissues and spaces
Administer so that maximal effect is at time of incision, and re-administer when appropriate
Alter dosage as appropriate for the patient (eg, obesity)

The authors report no financial relationships relevant to this article.

This article is adapted from DiRocco JD, Pavone LA, Weiss CA III. The evidence-based way to prevent SSI. Contemp Surg. 2005;61:120–127.

Of 72 different ways to prevent surgical site infections, 49 are backed by enough confirmatory science to merit the CDC’s strongest recommendation for use in all hospitals. (The 23 other measures in the CDC advisory have not been or cannot be as thoroughly studied.)

How can we apply all possible precautions to every patient wheeled into the OR? The CDC’s Guideline for Prevention of Surgical Site Infections (formerly termed wound infections) advocates “a systematic but realistic approach” based on the evidence, coupled with awareness that risk of surgical site infection is influenced by characteristics of the patient, operation, personnel, and hospital.

This article reviews key evidence behind a number of the most strongly recommended measures, such as optimal regimens for prophylactic antibiotics, and some of the recommendations for which equally rigorous evidence is lacking.

The CDC’s Guideline ranks its recommendations according to 4 levels of evidence. A total of 49 recommendations meet the most rigorous evidence standards, and therefore are “strongly recommended for all hospitals.” (See How strong is the evidence?.)

Many of our infection prevention routines, of course, have been standard ever since Joseph Lister introduced the principles of antisepsis in the late 1860s. Technically, however, some standard infection prevention routines are based on a strong theoretical rationale along with suggestive though not confirmatory science.

By necessity, narrowly defined patient populations and ethical and logistical issues will always limit our ability to obtain confirmatory scientific answers to some questions. For example, wearing gloves vs not wearing gloves fits into that category. Likewise, the evidence on preoperative nutritional support for the sole purpose of preventing SSI does not meet the criteria for the best evidence category, “1A.” Yet, nutrition therapy is among the CDC’s recommendations, albeit the evidence behind it falls into the “NR” category, “no recommendation; unresolved issue.”

The CDC’s exhaustive guideline identifies 21 characteristics of patients and operations that influence a patient’s risk of surgical site infection (TABLE 1), and recommends prevention tactics that are backed by evidence (See CDC Advisory).

The CDC’s recommendations are grouped into these sections:

1. Preoperative preparation of the patient, hand/forearm antisepsis for surgical team members, management of infected or colonized surgical personnel, and antimicrobial prophylaxis.

2. Intraoperative ventilation, cleaning and disinfection of environmental surfaces, microbiologic sampling, sterilization of surgical instruments, surgical attire and drapes, asepsis, and surgical technique.

3. Postoperative incision care.

4. Surveillance.

TABLE 1

21 factors that influence risk of surgical site infection

PATIENT
1 Age
2 Nutritional status
3 Diabetes
4 Smoking
5 Obesity
6 Coexistent infections at remote body site
7 Colonization with microorganisms
8 Altered immune response
9 Length of preoperative stay
OPERATION
10 Duration of surgical scrub
11 Skin antisepsis
12 Preoperative shaving
13 Duration of operation
14 Antimicrobial prophylaxis
15 Operating room ventilation
16 Inadequate sterilization of instruments
17 Foreign material in the surgical site
18 Surgical drains
19 Poor hemostasis
20 Failure to obliterate dead space
21 Tissue trauma
Source: Reference 1.

Preparing The Patient

Preoperative risk factors

Infection prevention begins with considering the preoperative risk factors of the patient’s condition.

Not all risk factors for surgical site infections can be modified (age, for example), but we should correct whatever we can before scheduling elective surgery.

Minimizing smoking improves postoperative SSI outcomes(EVIDENCE CATEGORY IB).

Weight loss before surgery has not been clearly correlated with improved SSI outcomes (EVIDENCE CATEGORY NR). However, body mass index may influence surgical complication rates, perhaps acting as a surrogate for technical difficulty or impaired wound-healing capacity.^2,3

Nutritionis being recognized as a key determinant in outcomes, but reports have not established how preoperative parenteral or enteral nutrition influences SSI outcome (NO RECOMMENDATION).^4,5

Antisepsis in the surgical field

The microbial source for most SSI is the patient’s endogenous flora, and the operative field determines the type of flora that will be encountered.

Normal skin flora consist mostly of gram-positive aerobes.

Antiseptic showering before surgery significantly reduces resident skin flora (EVIDENCE CATEGORY IB). Multiple showers with chlorhexidine have been shown to reduce resident bacteria up to 9-fold, but whether that reduces SSI rates is unclear.⁶

Prophylactic eradication of nasal Staph colonization (NO RECOMMENDATION). Recent attention has focused on microbial colonization with resistant organisms—and Staphylococcus aureus colonization of nares in cardiac surgery patients was found to be a major independent risk factor for surgical site infection.

 

Prophylactic intranasal mupirocin reduced infection risk in cardiothoracic patients,⁷ but preoperative use did not reduce gram-positive SSI rates in digestive tract surgery.⁸

Mupirocin also failed to reduce the wound rates in patients who had a variety of procedures, although the rate of nosocomial S aureus infections in the subset of patients with nasal colonization was reduced.⁹

Topical microbicides

Soap-and-water washing removes most debris from skin or other surgical surfaces, but antiseptic solutions reduce resident skin flora populations. The choice of appropriate topical microbicides during surgery can influence SSI rates (EVIDENCE CATEGORY IB).

When selecting an antiseptic, consider the anticipated duration of the case, the epithelial surface to be breeched (mucous membrane vs keratinized skin), and the anticipated flora.

Shaving and hair removal

Hair removal is often necessary, but shaving may cause skin trauma that exacerbates bacterial growth.¹⁰ SSI rates correlate with the time interval between shaving and incision (20% if shaved >24 hours before surgery, 7.1% the night before, and 3.1% in the OR).¹¹ Thus, the CDC guidelines discourage shaving prior to surgery (EVIDENCE CATEGORY IA).Patients have been known to shave the operative area themselves before surgery, so all patients must be told not to shave themselves before elective surgery.

When hair removal is necessary, preoperative clipping causes minimal skin trauma (EVIDENCE CATEGORY IA).

Preparing The Surgical Staff

The surgeon’s hands

Evidence has shown that 2 minutes of preoperative scrubbing reduces resident flora as effectively as scrubbing for 10 minutes.¹ The recommended scrub should include hands and forearms up to the elbows for 2 to 5 minutes (EVIDENCE CATEGORY IB).

Keep hands away from the body and dry hands with a sterile towel (EVIDENCE CATEGORY IB).

Keep fingernails short (EVIDENCE CATEGORY IB), and clean under each nail at the beginning of each day (EVIDENCE CATEGORY II).

An aqueous alcohol solution is a recent alternative to traditional hand antisepsis with chlorhexidine- or povoidoneiodine–based solutions. No difference in SSI rates has been documented between hand-rubbing with an aqueous alcohol solution and traditional scrubbing.¹² A traditional scrub before the first of consecutive cases and after contact with gross contamination is still in order.

Sterile barriers

Sterile barriers in the operating room, indispensable in protecting staff, are federally mandated. Their role in preventing SSI is not clear. Surprisingly, the use of face masks may not contribute to SSI reduction.¹³ Head covering, on the other hand, markedly reduces airborne and wound bacterial contamination.¹⁴

Optimize Wound Physiology

Maintaining normothermia

Hypothermia is common, particularly in patients who are immunocompromised, at age extremes, or have multiple trauma. Hypothermic vasoconstriction may reduce tissue perfusion and increase risk of infection.

A double-blind study showed that maintaining intraoperative normothermia decreased SSI in colorectal patients from 19% to 6%.¹⁵ Additionally, preoperative warming of the entire body or local site for 30 minutes reduced SSI rates in clean surgical cases.¹⁶

Wound space oxygenation

Supplemental oxygen in colorectal surgery may correlate with lower infection rates (80% without supplemental oxygen, 30% with).¹⁷ This may improve tissue oxygen tension, which enhances oxidative bactericidal capacity.

However, these findings were not duplicated in patients with higher SSI rates and on supplemental hyperoxia.¹⁸ There are no recommendations for enhancing wound space oxygenation.

Control of glycemia

Cardiothoracic surgery studies have stressed the importance of tight perioperative glycemic control. Coronary artery bypass patients with higher mean perioperative glucose showed a trend toward a higher risk of nosocomial infection, but not specifically SSI.¹⁹ Another study of cardiothoracic patients found an association between higher risk of SSI and both diabetes and postoperative hyperglycemia.²⁰ Continuous intravenous insulin to maintain a blood glucose 21

 

Remote infections

Remote infections at the time of surgery, such as urinary tract infection or pneumonia, significantly raise the risk of SSI (EVIDENCE CATEGORY IA).

Strongly consider canceling elective surgery if there is an untreated remote infection, especially if implanting bioprosthetic material.

Surgical technique

Careful technique reduces risk of infection.

Breaks in sterile technique and gross spillage of enteric contents raise the risk for SSI through increased bacterial load.

Poor hemostasis, excess tissue trauma, inadequate debridement or dead space obliteration, and inappropriate suture technique raise the volume of unperfused biological matter (EVIDENCE CATEGORY IB).

Timely completion of the operation also minimizes risk. Prolonged operative time can heighten the risk of breaches in sterile technique. Recommendations call for procedures to be completed within the 75th percentile of standardized operative times.

Antimicrobial prophylaxis

The principles for using preoperative antibiotics include maximal subcutaneous concentration when making the incision (TABLE 2) (EVIDENCE CATEGORY IA). This corresponds with intravenous antimicrobial administration within 60 minutes before incision (or within 120 minutes for vancomycin or fluoroquinolones). An additional dose of the antimicrobial agent is indicated if the procedure time exceeds 2 half-lives of the agent.

Institutional policies for antibiotic restriction aimed at curtailing resistant organisms do not appear to change the spectrum of causative microbes in SSI.²² Short-duration therapy preserves antimicrobial efficacy best, so avoid the routine use of agents such as vancomycin (EVIDENCE CATEGORY IB).

Short duration also applies when antimicrobial prophylaxis is indicated. The CDC recommends extending antimicrobial prophylaxis no more than a few hours after incision closure (EVIDENCE CATEGORY IA). Particular cases may require longer antimicrobial prophylaxis, but prophylaxis beyond 24 hours does not reduce SSI rates and increases the potential for microbial resistance.

While a single dose of broad-spectrum antibiotic may cause Clostridium difficile colitis, prolonged duration also raises risk through profound changes in gut flora that favor the emergence of this opportunistic pathogen.

TABLE 2

Principles of antimicrobial prophylaxis

Consider these factors:
Risk for developing surgical site infection.
Potential severity of consequences
Prosthetic implantation
Cardiothoracic or vascular surgery
Agents must be safe, inexpensive, and bactericidal
Appropriate spectrum based on anticipated flora of involved tissues and spaces
Administer so that maximal effect is at time of incision, and re-administer when appropriate
Alter dosage as appropriate for the patient (eg, obesity)

The authors report no financial relationships relevant to this article.

This article is adapted from DiRocco JD, Pavone LA, Weiss CA III. The evidence-based way to prevent SSI. Contemp Surg. 2005;61:120–127.

LISA’S CASE

Ablation fails to ease symptoms

Lisa is a 38-year-old mother of 2 who initially reported menometrorrhagia, dysmenorrhea, urinary frequency, pelvic pressure, and increasing abdominal girth. These symptoms worsened over 3 years before Lisa saw a physician and was diagnosed with uterine fibroids. When offered hysterectomy or endometrial ablation (cryomyolysis), she chose the latter. However, her fibroids failed to shrink, and her symptoms returned 5 months after the procedure.

Lisa heard about uterine artery embolization (UAE) through the media and now asks about it. Her uterus is 20-week size with an irregular contour. Magnetic resonance imaging (MRI) shows a single large fibroid filling the uterus. Her hematocrit is 22.

Is uterine UAE right for her?

ANGELINA’S CASE

Menorrhagia and a “boggy” uterus

Angelina, 35, has 2 children and a 10-year history of menorrhagia, dysmenorrhea, and anemia. Pelvic examination reveals a 10-week size, “boggy” uterus, and MRI shows global enlargement of the uterus with a thickened junctional zone, which is characteristic of adenomyosis.

Her previous physician recommended hysterectomy after medical therapy failed, but Angelina is reluctant to undergo surgery.

Is UAE an option?

Both women are very likely to benefit from UAE, since the ideal candidate is premenopausal with symptomatic fibroids and/or adenomyosis and has either failed medical or surgical therapy or wants or needs to avoid surgery.^1-11

This article describes the therapeutic role of UAE in women with abnormal uterine bleeding (AUB) due to uterine fibroids and/or adenomyosis—the most frequent myometrial causes of premenopausal AUB.

Other, less frequent myometrial disorders (eg, hypervascular pathologies such as intramyometrial and parametrial vascular malformations or neoplasms) can also be treated using embolization techniques. The main advantages of UAE in treating these diseases:^1-8,12,13

• Less invasive than surgery, with substantially less recovery time and lower morbidity
• Usually performed under local anesthesia and intravenous conscious sedation
• No worry about adhesions
• Virtually no blood loss or need for transfusion; UAE may be especially attractive for patients who refuse or cannot receive blood products for health or religious reasons.

Impressive success rates

UAE has demonstrated excellent technical (98% to 100%) and high clinical success rates (80% to 95%) in the treatment of fibroids.^1-8,13 The clinical success rate is lower for adenomyosis (56% to 92%), but UAE often provides sufficient clinical relief to obviate surgery.^9,10,13

Although UAE was not initially recommended for women desiring future fertility—because of the 4% risk of premature menopause—the pendulum is now swinging in the other direction. If the risks of myomectomy are great due to the anatomic size or position of fibroids or adenomyosis, the risk-benefit ratio may shift to UAE to allow preservation of reproductive capacity.^1-8,11

Though embolization has been performed since the early 1970s for acute and chronic bleeding associated with various medical conditions,¹⁴ the first report of UAE did not come until 1995.¹ Since then, the procedure has seen rapid growth worldwide, with approximately 50,000 cases performed. About 14,000 cases were performed in the US last year.²

Although our practice has no fixed size limitation, ideally a uterus less than 20 weeks’ gestational size is preferred.

Contraindications

• Viable pregnancy
• Active pelvic infection
• Presence of an intrauterine device (though the IUD may be removed before the rocedure)
• Undiagnosed pelvic or adnexal mass
• Pelvic malignancies such as ovarian or endometrial carcinoma
• History of pelvic radiation, since UAE may cause ischemic necrosis of the uterus and adjacent organs due to preexisting radiation-induced vasculitis with diffuse vascular narrowing.

Relative contraindications

• Renal insufficiency, though we have used gadolinium, a nonnephrotoxic MRI contrast medium, for women with high blood creatinine levels
• History of severe allergic reaction to iodinated contrast medium, though gadolinium can also be used in these patients
• Coagulopathy
• Desire to preserve fertility, since it cannot be assured based on current data. However, uncomplicated pregnancies and normal deliveries have been reported after UAE, so this procedure may still be preferred for women who refuse or cannot undergo myomectomy.¹¹

 

In some cases, extensive endometriosis is the cause of menorrhagia or dysmenorrhea, often coexisting with fibroids, and UAE may not be beneficial.¹¹

Finally, a subserosal leiomyoma that is sufficiently pedunculated (attachment point 50% of the diameter) can be at risk for detachment from the uterus, a situation that may necessitate surgical intervention.¹¹

Preop exam and imaging

At the physical examination, the fibroid uterus usually is enlarged with an irregular contour, and adenomyosis usually presents as a globally enlarged, “boggy” uterus (typically 6- to 10-weeks’ gestational size).

MRI is the preferred imaging

We prefer MRI since fibroids can be missed with ultrasound due to the limited field of view. MRI more accurately defines the size, location, and extent of disease. It also may better differentiate fibroids from adenomyosis.

MRI clearly depicts uterine zonal anatomy and enables accurate classification of individual masses by their locations: submucosal, intramural, or subserosal.

When adenomyosis is present, T2-weighted MRI demonstrates diffuse adenomyosis (about 66%) with global enlargement of the uterus and diffuse thickening of the junctional zone (at least 12 mm, highly predictive finding) with homogeneous low signal intensity. Focal adenomyosis (33%) can be seen as an illdefined, poorly marginated focal mass (adenomyoma) of low signal intensity within the myometrium.^15,16

Transvaginal ultrasound

In women with fibroids, ultrasound usually demonstrates an enlarged uterus with lobulations, contour abnormality, or mass effects.

In women with adenomyosis, it usually demonstrates ill-defined, heterogeneous echotexture and small anechoic areas within the myometrium of asymmetrically enlarged uteri, with indistinct endometrial-myometrial borders and subendometrial halo thickening.¹⁵

Include endometrial biopsy

The patient should have a normal Pap test during the 12 months leading up to UAE,¹¹ and should undergo endometrial biopsy to exclude carcinoma.

Laboratory tests should include a complete blood count, blood urea nitrogen/creatinine, follicle-stimulating hormone, human chorionic gonadotropin, and coagulation tests.

Technique

UAE begins with insertion of a small catheter (4-5 French) through a femoral artery in conjunction with percutaneous angiography. The catheter is guided into the uterine arteries—left first, then right— and contrast medium is injected into each artery to confirm the position of the catheter and the presence of fibroids or adenomyosis, which appear as hypervascular lesions in angiograms (see above, right).

UAE usually requires 1 to 2 hours.

Embolic agents

Polyvinyl alcohol (PVA) particles or trisacryl gelatin microspheres, usually 500 to 700 and/or 700 to 900 microns in size, are released through the catheter into the uterine arteries. These agents block the blood vessels that feed the fibroids and/or adenomyosis, causing them to shrink. The agents are biocompatible and have been approved by the US Food and Drug Administration.

Other, less frequently used embolic agents include gelatin sponge particles (which are temporary) and coils (which are permanent). Coils are generally used for conditions such as arteriovenous malformations or fistulae, which have large feeding vessels (iliac or enlarged uterine or ovarian vessels). This fluoroscopy-guided procedure usually is performed under local anesthesia and conscious sedation or, less often, epidural anesthesia.

Patient care

Conscious sedation, NSAIDs, and antibiotics

Intravenous conscious sedation in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) usually provides sufficient pain relief.

In addition, intravenous broad-spectrum antibiotics are used as prophylaxis for infection linked to the embolization itself and to subsequent ischemia of the fibroids and uterus.

Managing postop pain syndrome

More than 90% of women experience postembolization syndrome, which includes moderate to severe abdominal pain/cramping and nausea and vomiting in the first several hours following the procedure. As a result, they may require hospitalization (less than 24 hours) for pain management. In our experience, few women stay in the hospital more than 1 day.

A patient-controlled analgesia pump and NSAIDs are used in women with abdominal/pelvic cramping and pain (more than 90% of cases) if epidural anesthesia is not used for pain.

Low-grade fever and leukocytosis are not uncommon after embolization, and are usually treated with acetaminophen. Other symptoms are anorexia and fatigue, but they gradually subside within 3 to 4 days.

After discharge

Oral NSAIDs and narcotics are often needed for several days. Many women resume light activities in a few days, and most return to normal activities within 1 week.¹¹

Give her comprehensive discharge instructions on taking medications, what to expect, and when to contact a doctor. Follow-up visit in 1 to 4 weeks. We schedule an outpatient visit 1 to 4 weeks after the procedure. At this visit, we confirm healing of the puncture sites, screen for unusual symptoms or potential problems, and repeat follow-up instructions.¹¹

We then follow the patient periodically (3, 6, and 12 months) to monitor her for symptoms and complications such as late infections, expulsion of infarcted fibroids, chronic endometritis, chronic vaginal discharge, and cessation or irregularity of menses, all of which have been observed after UAE.¹¹

 

Transvaginal ultrasound is usually performed 3 to 6 months and 1 year after UAE to determine whether existing fibroids have been infarcted and begun to decrease in volume. It also reveals any uterine or adnexal complications.

In addition, this imaging provides a new baseline measurement of fibroid volume, against which any subsequent increase in size (which may indicate regrowth of fibroids or undiagnosed leiomyosarcoma) can be compared.¹¹

Key findings of outcome studies

Two large series reported significant improvement in AUB in 77% to 90% of fibroid cases, and bulk-related symptoms were controlled in 86% to 91%.^6-8 In these studies, average uterine volumes decreased by 35% and 58% at 3 and 12 months, respectively, with dominant fibroid shrinkage of 42%. Several large series also reported high patient satisfaction (91% to 93%) and significant improvement in quality-of-life measures.^4,6-8

Side effects and complications

Although UAE is considered very safe, it carries some risks. Spies et al¹⁷ reported on complications in 400 consecutive patients undergoing UAE for fibroids at their institution:

• 1.25% serious complication rate
• 5% overall periprocedural morbidity rate
• no deaths and no major permanent injuries

In addition, 1 patient required hysterectomy as a result of a complication, and 1 patient had an undiagnosed leiomyosarcoma, which was discovered during an elective myomectomy 31 months after UAE.

Goldberg et al ¹⁸ reported another case with delayed diagnosis of leiomyosarcoma following UAE. In our series of 705 patients, 1 had an undiagnosed leiomyosarcoma, which presented as a pelvic mass 15 months after UAE. She subsequently underwent hysterectomy.

When to suspect leiomyosarcoma

Unlike hysterectomy or myomectomy, no tissue is obtained in UAE for pathologic diagnosis to exclude leiomyosarcoma, which is found in approximately 0.1% to 0.4% of women with fibroids and is difficult to differentiate from a benign leiomyoma using clinical tests or imaging.^17-18

Suspect leiomyosarcoma if the fibroids continue to grow even after technically successful embolization.

Infection is rare, but can be lethal

A small number of patients have experienced infection, which usually is controlled with antibiotics. In a series of 414 UAE procedures in 410 fibroid patients, Rajan et al¹⁹ reported:

• 1.2% rate of intrauterine infection requiring intravenous antibiotic therapy and/or surgery
• no significant difference seen with various embolic agents, quantity of embolic particles, se of preprocedure antibiotics, or size or location of the dominant fibroid.

However, at least 2 deaths have been reported due to infection since UAE for fibroids was introduced in the mid-1990s: 1 fatal sepsis in a woman who underwent UAE for fibroids and 1 other sepsis fatality.^17,20 The first case was caused by necrosis of the vaginal wall and uterine cervix. At autopsy, microspheres were found not only in arteries in the leiomyomata and myometrium, but also in the parametria and vagina, causing ischemic necrosis.

Amenorrhea or worsened AUB

In some cases, amenorrhea can follow UAE for fibroids due to ovarian embolization and subsequent ovarian failure.^6-8,17

The literature indicates a rate of:

• 1% to 2% in patients less than 45 years of age
• 15% to 20% for perimenopausal women 45 and older

Worsening of uterine bleeding is rare after UAE, but can occur. Kerlan et al²¹ reported massive uterine bleeding 1 month after UAE in a woman who underwent the procedure for menorrhagia. When she was treated with emergent hysterectomy, a bleeding ulceration of the endometrium overlying the necrotic fibroid was found.

Other complications include spotting, hot flashes, fever, vaginal discharge, mood swings, pain at the puncture site, and dysuria.^6-8,17

Our UAE experience

The New England Fibroid Center began offering fibroid embolization in 1997. Since then, we have performed 705 procedures at 5 hospitals in the Greater Boston region, with a technical success rate of 99%. Technical failure occurred in 1% of patients; these women had very difficult vascular anatomy involving uterine arteries, or ovarian arteries formed the dominant blood supply to the fibroids.

Clinical success or improvement was seen in 80% of women with bulk-related symptoms and 94.3% with bleeding symptoms.

Clinical failure occurred in 5.7% of women (1.6% required repeat UAE and 1.4% hysterectomies due to persistent symptoms).

Complications occurred in 4% of cases (2% rate of premature ovarian failure, 1.5% rate of transvaginal passage of infarcted fibroids, and 0.5% rate of groin hematoma). There were no major complications requiring transfusion or emergent surgeries such as hysterectomy.

Fertility after UAE

LISA’S CASE

“Cure” and pregnancy

Lisa successfully underwent UAE, and had no symptoms after the procedure. The uterine fibroids resolved almost completely in 1 year.

Three years after the procedure, she became pregnant and delivered a healthy, full-term infant.

 

Although UAE is generally not performed in women who wish to preserve their fertility, it is sometimes used in fibroid patients when myomectomy is contraindicated because of the size and/or number of fibroids.^11,22,23 Only a few small series and case reports describe successful pregnancies following UAE.

For example, in a study involving 400 women, McLucas et al²² reported 17 pregnancies in 14 women among 149 patients who stated a desire for fertility after UAE. Of these, 5 spontaneous abortions were observed, and 10 women had normal term deliveries. No perfusion or other problems were reported during pregnancy or labor.

Goldberg and colleagues²³ analyzed 50 published cases of post-UAE pregnancies and found higher rates of cesarean delivery, preterm birth, malpresentation, small-for-gestational-age infants, spontaneous abortion, and postpartum hemorrhage than in the general population, though the reasons were unclear.

In our experience at the New England Fibroid Center, 5 of 12 patients below the age of 40 who wanted to preserve fertility became pregnant and successfully delivered full-term infants.

In general, the risks of infertility, premature ovarian failure/menopause, radiation exposure, and hysterectomy following UAE are small and compare favorably with those associated with myomectomy. Fertility rates are similar to those for women undergoing myomectomy.²⁴

Nevertheless, well-controlled studies and additional data are needed before UAE can be confidently recommended as a first-line approach for preserving fertility.¹¹

Treating adenomyosis

ANGELINA’S CASE

Adenomyosis resolves

During Angelina’s UAE procedure, angiographies showed enlarged right and left uterine arteries with numerous prominent intrauterine branches supplying the enlarged uterus. After UAE with PVA microspheres, post-embolization angiograms showed occlusion of the right and left uterine arteries and their branches.

Her symptoms resolved completely following the procedure. One year later, a follow-up MRI showed normal uterine size and shape, with complete resolution of adenomyosis.

Several small series have reported successful treatment of women with symptomatic adenomyosis. For example, of 23 women who underwent UAE for this indication, Chen and colleagues⁹ reported:

• Complete resolution of dysmenorrhea in 19 women and significant improvement in 2. Two other patients had recurrent symptoms.
• A substantial decrease in uterine volume in most of the women.
• An immediate decrease in intrauterine blood flow detected by color Doppler ultrasonography.

In a prospective study¹⁰ involving 18 women with symptomatic adenomyosis:

• 94% had diminished menorrhagia 6 months after UAE, and 94% had a slight decrease (mean: 15%) in uterine volume.
• After 1 year, 73% of women had diminished menorrhagia, and 53% had complete resolution.
• After 2 years, 56% of women had complete resolution of menorrhagia, 44% required additional treatment due to failure or recurrence, and 28% underwent hysterectomy.

In our limited experience with adenomyosis at the New England Fibroid Center, we saw no significant difference in technical success rates (100%) after UAE, compared with fibroid patients. However, there was a relatively high recurrence rate (2 of 6 patients) of presenting symptoms (menorrhagia or dysmenorrhea), and 2 patients later underwent hysterectomy.

Well-controlled studies are needed before UAE can confidently be recommended for symptomatic adenomyosis.

The authors report no financial relationships relevant to this article.

LISA’S CASE

Ablation fails to ease symptoms

Lisa is a 38-year-old mother of 2 who initially reported menometrorrhagia, dysmenorrhea, urinary frequency, pelvic pressure, and increasing abdominal girth. These symptoms worsened over 3 years before Lisa saw a physician and was diagnosed with uterine fibroids. When offered hysterectomy or endometrial ablation (cryomyolysis), she chose the latter. However, her fibroids failed to shrink, and her symptoms returned 5 months after the procedure.

Lisa heard about uterine artery embolization (UAE) through the media and now asks about it. Her uterus is 20-week size with an irregular contour. Magnetic resonance imaging (MRI) shows a single large fibroid filling the uterus. Her hematocrit is 22.

Is uterine UAE right for her?

ANGELINA’S CASE

Menorrhagia and a “boggy” uterus

Angelina, 35, has 2 children and a 10-year history of menorrhagia, dysmenorrhea, and anemia. Pelvic examination reveals a 10-week size, “boggy” uterus, and MRI shows global enlargement of the uterus with a thickened junctional zone, which is characteristic of adenomyosis.

Her previous physician recommended hysterectomy after medical therapy failed, but Angelina is reluctant to undergo surgery.

Is UAE an option?

Both women are very likely to benefit from UAE, since the ideal candidate is premenopausal with symptomatic fibroids and/or adenomyosis and has either failed medical or surgical therapy or wants or needs to avoid surgery.^1-11

This article describes the therapeutic role of UAE in women with abnormal uterine bleeding (AUB) due to uterine fibroids and/or adenomyosis—the most frequent myometrial causes of premenopausal AUB.

Other, less frequent myometrial disorders (eg, hypervascular pathologies such as intramyometrial and parametrial vascular malformations or neoplasms) can also be treated using embolization techniques. The main advantages of UAE in treating these diseases:^1-8,12,13

• Less invasive than surgery, with substantially less recovery time and lower morbidity
• Usually performed under local anesthesia and intravenous conscious sedation
• No worry about adhesions
• Virtually no blood loss or need for transfusion; UAE may be especially attractive for patients who refuse or cannot receive blood products for health or religious reasons.

Impressive success rates

UAE has demonstrated excellent technical (98% to 100%) and high clinical success rates (80% to 95%) in the treatment of fibroids.^1-8,13 The clinical success rate is lower for adenomyosis (56% to 92%), but UAE often provides sufficient clinical relief to obviate surgery.^9,10,13

Although UAE was not initially recommended for women desiring future fertility—because of the 4% risk of premature menopause—the pendulum is now swinging in the other direction. If the risks of myomectomy are great due to the anatomic size or position of fibroids or adenomyosis, the risk-benefit ratio may shift to UAE to allow preservation of reproductive capacity.^1-8,11

Though embolization has been performed since the early 1970s for acute and chronic bleeding associated with various medical conditions,¹⁴ the first report of UAE did not come until 1995.¹ Since then, the procedure has seen rapid growth worldwide, with approximately 50,000 cases performed. About 14,000 cases were performed in the US last year.²

Although our practice has no fixed size limitation, ideally a uterus less than 20 weeks’ gestational size is preferred.

Contraindications

• Viable pregnancy
• Active pelvic infection
• Presence of an intrauterine device (though the IUD may be removed before the rocedure)
• Undiagnosed pelvic or adnexal mass
• Pelvic malignancies such as ovarian or endometrial carcinoma
• History of pelvic radiation, since UAE may cause ischemic necrosis of the uterus and adjacent organs due to preexisting radiation-induced vasculitis with diffuse vascular narrowing.

Relative contraindications

• Renal insufficiency, though we have used gadolinium, a nonnephrotoxic MRI contrast medium, for women with high blood creatinine levels
• History of severe allergic reaction to iodinated contrast medium, though gadolinium can also be used in these patients
• Coagulopathy
• Desire to preserve fertility, since it cannot be assured based on current data. However, uncomplicated pregnancies and normal deliveries have been reported after UAE, so this procedure may still be preferred for women who refuse or cannot undergo myomectomy.¹¹

 

In some cases, extensive endometriosis is the cause of menorrhagia or dysmenorrhea, often coexisting with fibroids, and UAE may not be beneficial.¹¹

Finally, a subserosal leiomyoma that is sufficiently pedunculated (attachment point 50% of the diameter) can be at risk for detachment from the uterus, a situation that may necessitate surgical intervention.¹¹

Preop exam and imaging

At the physical examination, the fibroid uterus usually is enlarged with an irregular contour, and adenomyosis usually presents as a globally enlarged, “boggy” uterus (typically 6- to 10-weeks’ gestational size).

MRI is the preferred imaging

We prefer MRI since fibroids can be missed with ultrasound due to the limited field of view. MRI more accurately defines the size, location, and extent of disease. It also may better differentiate fibroids from adenomyosis.

MRI clearly depicts uterine zonal anatomy and enables accurate classification of individual masses by their locations: submucosal, intramural, or subserosal.

When adenomyosis is present, T2-weighted MRI demonstrates diffuse adenomyosis (about 66%) with global enlargement of the uterus and diffuse thickening of the junctional zone (at least 12 mm, highly predictive finding) with homogeneous low signal intensity. Focal adenomyosis (33%) can be seen as an illdefined, poorly marginated focal mass (adenomyoma) of low signal intensity within the myometrium.^15,16

Transvaginal ultrasound

In women with fibroids, ultrasound usually demonstrates an enlarged uterus with lobulations, contour abnormality, or mass effects.

In women with adenomyosis, it usually demonstrates ill-defined, heterogeneous echotexture and small anechoic areas within the myometrium of asymmetrically enlarged uteri, with indistinct endometrial-myometrial borders and subendometrial halo thickening.¹⁵

Include endometrial biopsy

The patient should have a normal Pap test during the 12 months leading up to UAE,¹¹ and should undergo endometrial biopsy to exclude carcinoma.

Laboratory tests should include a complete blood count, blood urea nitrogen/creatinine, follicle-stimulating hormone, human chorionic gonadotropin, and coagulation tests.

Technique

UAE begins with insertion of a small catheter (4-5 French) through a femoral artery in conjunction with percutaneous angiography. The catheter is guided into the uterine arteries—left first, then right— and contrast medium is injected into each artery to confirm the position of the catheter and the presence of fibroids or adenomyosis, which appear as hypervascular lesions in angiograms (see above, right).

UAE usually requires 1 to 2 hours.

Embolic agents

Polyvinyl alcohol (PVA) particles or trisacryl gelatin microspheres, usually 500 to 700 and/or 700 to 900 microns in size, are released through the catheter into the uterine arteries. These agents block the blood vessels that feed the fibroids and/or adenomyosis, causing them to shrink. The agents are biocompatible and have been approved by the US Food and Drug Administration.

Other, less frequently used embolic agents include gelatin sponge particles (which are temporary) and coils (which are permanent). Coils are generally used for conditions such as arteriovenous malformations or fistulae, which have large feeding vessels (iliac or enlarged uterine or ovarian vessels). This fluoroscopy-guided procedure usually is performed under local anesthesia and conscious sedation or, less often, epidural anesthesia.

Patient care

Conscious sedation, NSAIDs, and antibiotics

Intravenous conscious sedation in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) usually provides sufficient pain relief.

In addition, intravenous broad-spectrum antibiotics are used as prophylaxis for infection linked to the embolization itself and to subsequent ischemia of the fibroids and uterus.

Managing postop pain syndrome

More than 90% of women experience postembolization syndrome, which includes moderate to severe abdominal pain/cramping and nausea and vomiting in the first several hours following the procedure. As a result, they may require hospitalization (less than 24 hours) for pain management. In our experience, few women stay in the hospital more than 1 day.

A patient-controlled analgesia pump and NSAIDs are used in women with abdominal/pelvic cramping and pain (more than 90% of cases) if epidural anesthesia is not used for pain.

Low-grade fever and leukocytosis are not uncommon after embolization, and are usually treated with acetaminophen. Other symptoms are anorexia and fatigue, but they gradually subside within 3 to 4 days.

After discharge

Oral NSAIDs and narcotics are often needed for several days. Many women resume light activities in a few days, and most return to normal activities within 1 week.¹¹

Give her comprehensive discharge instructions on taking medications, what to expect, and when to contact a doctor. Follow-up visit in 1 to 4 weeks. We schedule an outpatient visit 1 to 4 weeks after the procedure. At this visit, we confirm healing of the puncture sites, screen for unusual symptoms or potential problems, and repeat follow-up instructions.¹¹

We then follow the patient periodically (3, 6, and 12 months) to monitor her for symptoms and complications such as late infections, expulsion of infarcted fibroids, chronic endometritis, chronic vaginal discharge, and cessation or irregularity of menses, all of which have been observed after UAE.¹¹

 

Transvaginal ultrasound is usually performed 3 to 6 months and 1 year after UAE to determine whether existing fibroids have been infarcted and begun to decrease in volume. It also reveals any uterine or adnexal complications.

In addition, this imaging provides a new baseline measurement of fibroid volume, against which any subsequent increase in size (which may indicate regrowth of fibroids or undiagnosed leiomyosarcoma) can be compared.¹¹

Key findings of outcome studies

Two large series reported significant improvement in AUB in 77% to 90% of fibroid cases, and bulk-related symptoms were controlled in 86% to 91%.^6-8 In these studies, average uterine volumes decreased by 35% and 58% at 3 and 12 months, respectively, with dominant fibroid shrinkage of 42%. Several large series also reported high patient satisfaction (91% to 93%) and significant improvement in quality-of-life measures.^4,6-8

Side effects and complications

Although UAE is considered very safe, it carries some risks. Spies et al¹⁷ reported on complications in 400 consecutive patients undergoing UAE for fibroids at their institution:

• 1.25% serious complication rate
• 5% overall periprocedural morbidity rate
• no deaths and no major permanent injuries

In addition, 1 patient required hysterectomy as a result of a complication, and 1 patient had an undiagnosed leiomyosarcoma, which was discovered during an elective myomectomy 31 months after UAE.

Goldberg et al ¹⁸ reported another case with delayed diagnosis of leiomyosarcoma following UAE. In our series of 705 patients, 1 had an undiagnosed leiomyosarcoma, which presented as a pelvic mass 15 months after UAE. She subsequently underwent hysterectomy.

When to suspect leiomyosarcoma

Unlike hysterectomy or myomectomy, no tissue is obtained in UAE for pathologic diagnosis to exclude leiomyosarcoma, which is found in approximately 0.1% to 0.4% of women with fibroids and is difficult to differentiate from a benign leiomyoma using clinical tests or imaging.^17-18

Suspect leiomyosarcoma if the fibroids continue to grow even after technically successful embolization.

Infection is rare, but can be lethal

A small number of patients have experienced infection, which usually is controlled with antibiotics. In a series of 414 UAE procedures in 410 fibroid patients, Rajan et al¹⁹ reported:

• 1.2% rate of intrauterine infection requiring intravenous antibiotic therapy and/or surgery
• no significant difference seen with various embolic agents, quantity of embolic particles, se of preprocedure antibiotics, or size or location of the dominant fibroid.

However, at least 2 deaths have been reported due to infection since UAE for fibroids was introduced in the mid-1990s: 1 fatal sepsis in a woman who underwent UAE for fibroids and 1 other sepsis fatality.^17,20 The first case was caused by necrosis of the vaginal wall and uterine cervix. At autopsy, microspheres were found not only in arteries in the leiomyomata and myometrium, but also in the parametria and vagina, causing ischemic necrosis.

Amenorrhea or worsened AUB

In some cases, amenorrhea can follow UAE for fibroids due to ovarian embolization and subsequent ovarian failure.^6-8,17

The literature indicates a rate of:

• 1% to 2% in patients less than 45 years of age
• 15% to 20% for perimenopausal women 45 and older

Worsening of uterine bleeding is rare after UAE, but can occur. Kerlan et al²¹ reported massive uterine bleeding 1 month after UAE in a woman who underwent the procedure for menorrhagia. When she was treated with emergent hysterectomy, a bleeding ulceration of the endometrium overlying the necrotic fibroid was found.

Other complications include spotting, hot flashes, fever, vaginal discharge, mood swings, pain at the puncture site, and dysuria.^6-8,17

Our UAE experience

The New England Fibroid Center began offering fibroid embolization in 1997. Since then, we have performed 705 procedures at 5 hospitals in the Greater Boston region, with a technical success rate of 99%. Technical failure occurred in 1% of patients; these women had very difficult vascular anatomy involving uterine arteries, or ovarian arteries formed the dominant blood supply to the fibroids.

Clinical success or improvement was seen in 80% of women with bulk-related symptoms and 94.3% with bleeding symptoms.

Clinical failure occurred in 5.7% of women (1.6% required repeat UAE and 1.4% hysterectomies due to persistent symptoms).

Complications occurred in 4% of cases (2% rate of premature ovarian failure, 1.5% rate of transvaginal passage of infarcted fibroids, and 0.5% rate of groin hematoma). There were no major complications requiring transfusion or emergent surgeries such as hysterectomy.

Fertility after UAE

LISA’S CASE

“Cure” and pregnancy

Lisa successfully underwent UAE, and had no symptoms after the procedure. The uterine fibroids resolved almost completely in 1 year.

Three years after the procedure, she became pregnant and delivered a healthy, full-term infant.

 

Although UAE is generally not performed in women who wish to preserve their fertility, it is sometimes used in fibroid patients when myomectomy is contraindicated because of the size and/or number of fibroids.^11,22,23 Only a few small series and case reports describe successful pregnancies following UAE.

For example, in a study involving 400 women, McLucas et al²² reported 17 pregnancies in 14 women among 149 patients who stated a desire for fertility after UAE. Of these, 5 spontaneous abortions were observed, and 10 women had normal term deliveries. No perfusion or other problems were reported during pregnancy or labor.

Goldberg and colleagues²³ analyzed 50 published cases of post-UAE pregnancies and found higher rates of cesarean delivery, preterm birth, malpresentation, small-for-gestational-age infants, spontaneous abortion, and postpartum hemorrhage than in the general population, though the reasons were unclear.

In our experience at the New England Fibroid Center, 5 of 12 patients below the age of 40 who wanted to preserve fertility became pregnant and successfully delivered full-term infants.

In general, the risks of infertility, premature ovarian failure/menopause, radiation exposure, and hysterectomy following UAE are small and compare favorably with those associated with myomectomy. Fertility rates are similar to those for women undergoing myomectomy.²⁴

Nevertheless, well-controlled studies and additional data are needed before UAE can be confidently recommended as a first-line approach for preserving fertility.¹¹

Treating adenomyosis

ANGELINA’S CASE

Adenomyosis resolves

During Angelina’s UAE procedure, angiographies showed enlarged right and left uterine arteries with numerous prominent intrauterine branches supplying the enlarged uterus. After UAE with PVA microspheres, post-embolization angiograms showed occlusion of the right and left uterine arteries and their branches.

Her symptoms resolved completely following the procedure. One year later, a follow-up MRI showed normal uterine size and shape, with complete resolution of adenomyosis.

Several small series have reported successful treatment of women with symptomatic adenomyosis. For example, of 23 women who underwent UAE for this indication, Chen and colleagues⁹ reported:

• Complete resolution of dysmenorrhea in 19 women and significant improvement in 2. Two other patients had recurrent symptoms.
• A substantial decrease in uterine volume in most of the women.
• An immediate decrease in intrauterine blood flow detected by color Doppler ultrasonography.

In a prospective study¹⁰ involving 18 women with symptomatic adenomyosis:

• 94% had diminished menorrhagia 6 months after UAE, and 94% had a slight decrease (mean: 15%) in uterine volume.
• After 1 year, 73% of women had diminished menorrhagia, and 53% had complete resolution.
• After 2 years, 56% of women had complete resolution of menorrhagia, 44% required additional treatment due to failure or recurrence, and 28% underwent hysterectomy.

In our limited experience with adenomyosis at the New England Fibroid Center, we saw no significant difference in technical success rates (100%) after UAE, compared with fibroid patients. However, there was a relatively high recurrence rate (2 of 6 patients) of presenting symptoms (menorrhagia or dysmenorrhea), and 2 patients later underwent hysterectomy.

Well-controlled studies are needed before UAE can confidently be recommended for symptomatic adenomyosis.

The authors report no financial relationships relevant to this article.

LISA’S CASE

Ablation fails to ease symptoms

Lisa is a 38-year-old mother of 2 who initially reported menometrorrhagia, dysmenorrhea, urinary frequency, pelvic pressure, and increasing abdominal girth. These symptoms worsened over 3 years before Lisa saw a physician and was diagnosed with uterine fibroids. When offered hysterectomy or endometrial ablation (cryomyolysis), she chose the latter. However, her fibroids failed to shrink, and her symptoms returned 5 months after the procedure.

Lisa heard about uterine artery embolization (UAE) through the media and now asks about it. Her uterus is 20-week size with an irregular contour. Magnetic resonance imaging (MRI) shows a single large fibroid filling the uterus. Her hematocrit is 22.

Is uterine UAE right for her?

ANGELINA’S CASE

Menorrhagia and a “boggy” uterus

Angelina, 35, has 2 children and a 10-year history of menorrhagia, dysmenorrhea, and anemia. Pelvic examination reveals a 10-week size, “boggy” uterus, and MRI shows global enlargement of the uterus with a thickened junctional zone, which is characteristic of adenomyosis.

Her previous physician recommended hysterectomy after medical therapy failed, but Angelina is reluctant to undergo surgery.

Is UAE an option?

Both women are very likely to benefit from UAE, since the ideal candidate is premenopausal with symptomatic fibroids and/or adenomyosis and has either failed medical or surgical therapy or wants or needs to avoid surgery.^1-11

This article describes the therapeutic role of UAE in women with abnormal uterine bleeding (AUB) due to uterine fibroids and/or adenomyosis—the most frequent myometrial causes of premenopausal AUB.

Other, less frequent myometrial disorders (eg, hypervascular pathologies such as intramyometrial and parametrial vascular malformations or neoplasms) can also be treated using embolization techniques. The main advantages of UAE in treating these diseases:^1-8,12,13

• Less invasive than surgery, with substantially less recovery time and lower morbidity
• Usually performed under local anesthesia and intravenous conscious sedation
• No worry about adhesions
• Virtually no blood loss or need for transfusion; UAE may be especially attractive for patients who refuse or cannot receive blood products for health or religious reasons.

Impressive success rates

UAE has demonstrated excellent technical (98% to 100%) and high clinical success rates (80% to 95%) in the treatment of fibroids.^1-8,13 The clinical success rate is lower for adenomyosis (56% to 92%), but UAE often provides sufficient clinical relief to obviate surgery.^9,10,13

Although UAE was not initially recommended for women desiring future fertility—because of the 4% risk of premature menopause—the pendulum is now swinging in the other direction. If the risks of myomectomy are great due to the anatomic size or position of fibroids or adenomyosis, the risk-benefit ratio may shift to UAE to allow preservation of reproductive capacity.^1-8,11

Though embolization has been performed since the early 1970s for acute and chronic bleeding associated with various medical conditions,¹⁴ the first report of UAE did not come until 1995.¹ Since then, the procedure has seen rapid growth worldwide, with approximately 50,000 cases performed. About 14,000 cases were performed in the US last year.²

Although our practice has no fixed size limitation, ideally a uterus less than 20 weeks’ gestational size is preferred.

Contraindications

• Viable pregnancy
• Active pelvic infection
• Presence of an intrauterine device (though the IUD may be removed before the rocedure)
• Undiagnosed pelvic or adnexal mass
• Pelvic malignancies such as ovarian or endometrial carcinoma
• History of pelvic radiation, since UAE may cause ischemic necrosis of the uterus and adjacent organs due to preexisting radiation-induced vasculitis with diffuse vascular narrowing.

Relative contraindications

• Renal insufficiency, though we have used gadolinium, a nonnephrotoxic MRI contrast medium, for women with high blood creatinine levels
• History of severe allergic reaction to iodinated contrast medium, though gadolinium can also be used in these patients
• Coagulopathy
• Desire to preserve fertility, since it cannot be assured based on current data. However, uncomplicated pregnancies and normal deliveries have been reported after UAE, so this procedure may still be preferred for women who refuse or cannot undergo myomectomy.¹¹

 

In some cases, extensive endometriosis is the cause of menorrhagia or dysmenorrhea, often coexisting with fibroids, and UAE may not be beneficial.¹¹

Finally, a subserosal leiomyoma that is sufficiently pedunculated (attachment point 50% of the diameter) can be at risk for detachment from the uterus, a situation that may necessitate surgical intervention.¹¹

Preop exam and imaging

At the physical examination, the fibroid uterus usually is enlarged with an irregular contour, and adenomyosis usually presents as a globally enlarged, “boggy” uterus (typically 6- to 10-weeks’ gestational size).

MRI is the preferred imaging

We prefer MRI since fibroids can be missed with ultrasound due to the limited field of view. MRI more accurately defines the size, location, and extent of disease. It also may better differentiate fibroids from adenomyosis.

MRI clearly depicts uterine zonal anatomy and enables accurate classification of individual masses by their locations: submucosal, intramural, or subserosal.

When adenomyosis is present, T2-weighted MRI demonstrates diffuse adenomyosis (about 66%) with global enlargement of the uterus and diffuse thickening of the junctional zone (at least 12 mm, highly predictive finding) with homogeneous low signal intensity. Focal adenomyosis (33%) can be seen as an illdefined, poorly marginated focal mass (adenomyoma) of low signal intensity within the myometrium.^15,16

Transvaginal ultrasound

In women with fibroids, ultrasound usually demonstrates an enlarged uterus with lobulations, contour abnormality, or mass effects.

In women with adenomyosis, it usually demonstrates ill-defined, heterogeneous echotexture and small anechoic areas within the myometrium of asymmetrically enlarged uteri, with indistinct endometrial-myometrial borders and subendometrial halo thickening.¹⁵

Include endometrial biopsy

The patient should have a normal Pap test during the 12 months leading up to UAE,¹¹ and should undergo endometrial biopsy to exclude carcinoma.

Laboratory tests should include a complete blood count, blood urea nitrogen/creatinine, follicle-stimulating hormone, human chorionic gonadotropin, and coagulation tests.

Technique

UAE begins with insertion of a small catheter (4-5 French) through a femoral artery in conjunction with percutaneous angiography. The catheter is guided into the uterine arteries—left first, then right— and contrast medium is injected into each artery to confirm the position of the catheter and the presence of fibroids or adenomyosis, which appear as hypervascular lesions in angiograms (see above, right).

UAE usually requires 1 to 2 hours.

Embolic agents

Polyvinyl alcohol (PVA) particles or trisacryl gelatin microspheres, usually 500 to 700 and/or 700 to 900 microns in size, are released through the catheter into the uterine arteries. These agents block the blood vessels that feed the fibroids and/or adenomyosis, causing them to shrink. The agents are biocompatible and have been approved by the US Food and Drug Administration.

Other, less frequently used embolic agents include gelatin sponge particles (which are temporary) and coils (which are permanent). Coils are generally used for conditions such as arteriovenous malformations or fistulae, which have large feeding vessels (iliac or enlarged uterine or ovarian vessels). This fluoroscopy-guided procedure usually is performed under local anesthesia and conscious sedation or, less often, epidural anesthesia.

Patient care

Conscious sedation, NSAIDs, and antibiotics

Intravenous conscious sedation in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) usually provides sufficient pain relief.

In addition, intravenous broad-spectrum antibiotics are used as prophylaxis for infection linked to the embolization itself and to subsequent ischemia of the fibroids and uterus.

Managing postop pain syndrome

More than 90% of women experience postembolization syndrome, which includes moderate to severe abdominal pain/cramping and nausea and vomiting in the first several hours following the procedure. As a result, they may require hospitalization (less than 24 hours) for pain management. In our experience, few women stay in the hospital more than 1 day.

A patient-controlled analgesia pump and NSAIDs are used in women with abdominal/pelvic cramping and pain (more than 90% of cases) if epidural anesthesia is not used for pain.

Low-grade fever and leukocytosis are not uncommon after embolization, and are usually treated with acetaminophen. Other symptoms are anorexia and fatigue, but they gradually subside within 3 to 4 days.

After discharge

Oral NSAIDs and narcotics are often needed for several days. Many women resume light activities in a few days, and most return to normal activities within 1 week.¹¹

Give her comprehensive discharge instructions on taking medications, what to expect, and when to contact a doctor. Follow-up visit in 1 to 4 weeks. We schedule an outpatient visit 1 to 4 weeks after the procedure. At this visit, we confirm healing of the puncture sites, screen for unusual symptoms or potential problems, and repeat follow-up instructions.¹¹

We then follow the patient periodically (3, 6, and 12 months) to monitor her for symptoms and complications such as late infections, expulsion of infarcted fibroids, chronic endometritis, chronic vaginal discharge, and cessation or irregularity of menses, all of which have been observed after UAE.¹¹

 

Transvaginal ultrasound is usually performed 3 to 6 months and 1 year after UAE to determine whether existing fibroids have been infarcted and begun to decrease in volume. It also reveals any uterine or adnexal complications.

In addition, this imaging provides a new baseline measurement of fibroid volume, against which any subsequent increase in size (which may indicate regrowth of fibroids or undiagnosed leiomyosarcoma) can be compared.¹¹

Key findings of outcome studies

Two large series reported significant improvement in AUB in 77% to 90% of fibroid cases, and bulk-related symptoms were controlled in 86% to 91%.^6-8 In these studies, average uterine volumes decreased by 35% and 58% at 3 and 12 months, respectively, with dominant fibroid shrinkage of 42%. Several large series also reported high patient satisfaction (91% to 93%) and significant improvement in quality-of-life measures.^4,6-8

Side effects and complications

Although UAE is considered very safe, it carries some risks. Spies et al¹⁷ reported on complications in 400 consecutive patients undergoing UAE for fibroids at their institution:

• 1.25% serious complication rate
• 5% overall periprocedural morbidity rate
• no deaths and no major permanent injuries

In addition, 1 patient required hysterectomy as a result of a complication, and 1 patient had an undiagnosed leiomyosarcoma, which was discovered during an elective myomectomy 31 months after UAE.

Goldberg et al ¹⁸ reported another case with delayed diagnosis of leiomyosarcoma following UAE. In our series of 705 patients, 1 had an undiagnosed leiomyosarcoma, which presented as a pelvic mass 15 months after UAE. She subsequently underwent hysterectomy.

When to suspect leiomyosarcoma

Unlike hysterectomy or myomectomy, no tissue is obtained in UAE for pathologic diagnosis to exclude leiomyosarcoma, which is found in approximately 0.1% to 0.4% of women with fibroids and is difficult to differentiate from a benign leiomyoma using clinical tests or imaging.^17-18

Suspect leiomyosarcoma if the fibroids continue to grow even after technically successful embolization.

Infection is rare, but can be lethal

A small number of patients have experienced infection, which usually is controlled with antibiotics. In a series of 414 UAE procedures in 410 fibroid patients, Rajan et al¹⁹ reported:

• 1.2% rate of intrauterine infection requiring intravenous antibiotic therapy and/or surgery
• no significant difference seen with various embolic agents, quantity of embolic particles, se of preprocedure antibiotics, or size or location of the dominant fibroid.

However, at least 2 deaths have been reported due to infection since UAE for fibroids was introduced in the mid-1990s: 1 fatal sepsis in a woman who underwent UAE for fibroids and 1 other sepsis fatality.^17,20 The first case was caused by necrosis of the vaginal wall and uterine cervix. At autopsy, microspheres were found not only in arteries in the leiomyomata and myometrium, but also in the parametria and vagina, causing ischemic necrosis.

Amenorrhea or worsened AUB

In some cases, amenorrhea can follow UAE for fibroids due to ovarian embolization and subsequent ovarian failure.^6-8,17

The literature indicates a rate of:

• 1% to 2% in patients less than 45 years of age
• 15% to 20% for perimenopausal women 45 and older

Worsening of uterine bleeding is rare after UAE, but can occur. Kerlan et al²¹ reported massive uterine bleeding 1 month after UAE in a woman who underwent the procedure for menorrhagia. When she was treated with emergent hysterectomy, a bleeding ulceration of the endometrium overlying the necrotic fibroid was found.

Other complications include spotting, hot flashes, fever, vaginal discharge, mood swings, pain at the puncture site, and dysuria.^6-8,17

Our UAE experience

The New England Fibroid Center began offering fibroid embolization in 1997. Since then, we have performed 705 procedures at 5 hospitals in the Greater Boston region, with a technical success rate of 99%. Technical failure occurred in 1% of patients; these women had very difficult vascular anatomy involving uterine arteries, or ovarian arteries formed the dominant blood supply to the fibroids.

Clinical success or improvement was seen in 80% of women with bulk-related symptoms and 94.3% with bleeding symptoms.

Clinical failure occurred in 5.7% of women (1.6% required repeat UAE and 1.4% hysterectomies due to persistent symptoms).

Complications occurred in 4% of cases (2% rate of premature ovarian failure, 1.5% rate of transvaginal passage of infarcted fibroids, and 0.5% rate of groin hematoma). There were no major complications requiring transfusion or emergent surgeries such as hysterectomy.

Fertility after UAE

LISA’S CASE

“Cure” and pregnancy

Lisa successfully underwent UAE, and had no symptoms after the procedure. The uterine fibroids resolved almost completely in 1 year.

Three years after the procedure, she became pregnant and delivered a healthy, full-term infant.

 

Although UAE is generally not performed in women who wish to preserve their fertility, it is sometimes used in fibroid patients when myomectomy is contraindicated because of the size and/or number of fibroids.^11,22,23 Only a few small series and case reports describe successful pregnancies following UAE.

For example, in a study involving 400 women, McLucas et al²² reported 17 pregnancies in 14 women among 149 patients who stated a desire for fertility after UAE. Of these, 5 spontaneous abortions were observed, and 10 women had normal term deliveries. No perfusion or other problems were reported during pregnancy or labor.

Goldberg and colleagues²³ analyzed 50 published cases of post-UAE pregnancies and found higher rates of cesarean delivery, preterm birth, malpresentation, small-for-gestational-age infants, spontaneous abortion, and postpartum hemorrhage than in the general population, though the reasons were unclear.

In our experience at the New England Fibroid Center, 5 of 12 patients below the age of 40 who wanted to preserve fertility became pregnant and successfully delivered full-term infants.

In general, the risks of infertility, premature ovarian failure/menopause, radiation exposure, and hysterectomy following UAE are small and compare favorably with those associated with myomectomy. Fertility rates are similar to those for women undergoing myomectomy.²⁴

Nevertheless, well-controlled studies and additional data are needed before UAE can be confidently recommended as a first-line approach for preserving fertility.¹¹

Treating adenomyosis

ANGELINA’S CASE

Adenomyosis resolves

During Angelina’s UAE procedure, angiographies showed enlarged right and left uterine arteries with numerous prominent intrauterine branches supplying the enlarged uterus. After UAE with PVA microspheres, post-embolization angiograms showed occlusion of the right and left uterine arteries and their branches.

Her symptoms resolved completely following the procedure. One year later, a follow-up MRI showed normal uterine size and shape, with complete resolution of adenomyosis.

Several small series have reported successful treatment of women with symptomatic adenomyosis. For example, of 23 women who underwent UAE for this indication, Chen and colleagues⁹ reported:

• Complete resolution of dysmenorrhea in 19 women and significant improvement in 2. Two other patients had recurrent symptoms.
• A substantial decrease in uterine volume in most of the women.
• An immediate decrease in intrauterine blood flow detected by color Doppler ultrasonography.

In a prospective study¹⁰ involving 18 women with symptomatic adenomyosis:

• 94% had diminished menorrhagia 6 months after UAE, and 94% had a slight decrease (mean: 15%) in uterine volume.
• After 1 year, 73% of women had diminished menorrhagia, and 53% had complete resolution.
• After 2 years, 56% of women had complete resolution of menorrhagia, 44% required additional treatment due to failure or recurrence, and 28% underwent hysterectomy.

In our limited experience with adenomyosis at the New England Fibroid Center, we saw no significant difference in technical success rates (100%) after UAE, compared with fibroid patients. However, there was a relatively high recurrence rate (2 of 6 patients) of presenting symptoms (menorrhagia or dysmenorrhea), and 2 patients later underwent hysterectomy.

Well-controlled studies are needed before UAE can confidently be recommended for symptomatic adenomyosis.

The authors report no financial relationships relevant to this article.

SALLY’S CASE

Placenta accreta leads to hemorrhage

Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.

The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.

Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.

What is the best way to manage the hemorrhage?

After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.

If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.

STEP 1Like the Boy Scouts, Be Prepared

Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.

Besides asking about the patient’s medications, assess the following:

• Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.¹ I recommend platelet evaluation for patients scheduled for major abdominal surgery.
  
• History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
  
• High alcohol intake warrants preoperative liver function and coagulation studies.
  
• Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.²
  
• Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
  
• Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
  
• Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
  

For patients predisposed to bleeding, obtaining exposure is mandatory. Blood components and a cell-saving device also should be available, as described below.

TABLE 1

Alternative remedies that may exacerbate bleeding

• 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
  
• Stop all alternative remedies 2 to 7 days before surgery
  

REMEDY	USED FOR	PERIOPERATIVE RISKS
Beta-carotene	Vitamin A precursor; often taken as a nutritional supplement	May cause coagulopathy
Feverfew	Used to prevent or treat migraine and ease menstrual cramps	May inhibit coagulation
Fish oil	Rich in omega-3 fatty acids, recommended for cardiovascular health	Omega-3s inhibit coagulation
Garlic	Used to reduce hypertension and high cholesterol	Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation
Ginkgo	Treatment of dementia, impaired cognition, and memory	Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding
Ginseng	Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster	May cause hypertension, cardiovascular instability, coagulopathy, and sedation
St. John’s wort	Antidepressant	May cause cardiovascular instability, coagulopathy, and sedation
Vitamin E	Antioxidant	May interfere with coagulation

STEP 2Follow These Basic Principles

Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.

 

If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).

Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.

If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.

Great vessel injuries

The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.³

Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.

In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.

Replacing blood and its components

Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:

• For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
  
• If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
  
• With prolonged PTT, give fresh frozen plasma.
  
• If fibrinogen is low, give 2 U of cryoprecipitate.¹
  

Primary volume expansion should be performed before replacing blood or blood components. One option when facing massive hemorrhage is to give cryoprecipitate initially.

When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,⁴ and has been used safely in women with cesarean-associated bleeding.⁵ Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.⁶ The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.

STEP 3Try A Topical Hemostatic Agent

If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.

My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.

Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.

To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.

The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.

TABLE 2

Topical intraperitoneal hemostatic agents

AGENT	WHAT IT IS	HOW IT IS APPLIED
Avitene Ultrafoam	Absorbable collagen hemostat	Comes in powder; sprinkle on area
Fibrin glue Coseal Floseal Tisseal	Equal amounts of cryoprecipitate and thrombin	Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare
Gelfoam	Absorbable gelatin sponge	Cut in strips of appropriate size and apply to area
Surgicel	Oxidized regenerated cellulose	Cut in strips of appropriate size and apply to area

STEP 4Hypogastric Artery Ligation

SALLY’S CASE

Bleeding persists

Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.

If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.^7,8

 

STEP 5When All Else Fails: “Pack And Go”

If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.^10-12

A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.

For the Logothetopolous or “parachute” pack,^13,14 about 6 yards of 4-inch gauze is packed in the center of a 24-inch square laparotomy tape or a sterile bowel isolation bag, tied, and pulled through the vagina. Pressure is maintained with a weight tied to the end that is brought out through the vagina. One problem with the parachute pack is that further bleeding or injury to the bowel upon removal may not be recognized early.

SALLY’S CASE

Hemorrhage abates

A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.

She undergoes reoperation 36 hours later, at which time no bleeding is encountered.

The left ureter is reimplanted into the bladder, and she makes a full recovery.

The author has served on the speakers bureau for Wyeth.

SALLY’S CASE

Placenta accreta leads to hemorrhage

Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.

The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.

Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.

What is the best way to manage the hemorrhage?

After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.

If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.

STEP 1Like the Boy Scouts, Be Prepared

Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.

Besides asking about the patient’s medications, assess the following:

• Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.¹ I recommend platelet evaluation for patients scheduled for major abdominal surgery.
  
• History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
  
• High alcohol intake warrants preoperative liver function and coagulation studies.
  
• Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.²
  
• Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
  
• Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
  
• Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
  

For patients predisposed to bleeding, obtaining exposure is mandatory. Blood components and a cell-saving device also should be available, as described below.

TABLE 1

Alternative remedies that may exacerbate bleeding

• 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
  
• Stop all alternative remedies 2 to 7 days before surgery
  

REMEDY	USED FOR	PERIOPERATIVE RISKS
Beta-carotene	Vitamin A precursor; often taken as a nutritional supplement	May cause coagulopathy
Feverfew	Used to prevent or treat migraine and ease menstrual cramps	May inhibit coagulation
Fish oil	Rich in omega-3 fatty acids, recommended for cardiovascular health	Omega-3s inhibit coagulation
Garlic	Used to reduce hypertension and high cholesterol	Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation
Ginkgo	Treatment of dementia, impaired cognition, and memory	Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding
Ginseng	Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster	May cause hypertension, cardiovascular instability, coagulopathy, and sedation
St. John’s wort	Antidepressant	May cause cardiovascular instability, coagulopathy, and sedation
Vitamin E	Antioxidant	May interfere with coagulation

STEP 2Follow These Basic Principles

Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.

 

If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).

Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.

If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.

Great vessel injuries

The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.³

Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.

In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.

Replacing blood and its components

Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:

• For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
  
• If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
  
• With prolonged PTT, give fresh frozen plasma.
  
• If fibrinogen is low, give 2 U of cryoprecipitate.¹
  

Primary volume expansion should be performed before replacing blood or blood components. One option when facing massive hemorrhage is to give cryoprecipitate initially.

When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,⁴ and has been used safely in women with cesarean-associated bleeding.⁵ Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.⁶ The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.

STEP 3Try A Topical Hemostatic Agent

If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.

My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.

Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.

To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.

The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.

TABLE 2

Topical intraperitoneal hemostatic agents

AGENT	WHAT IT IS	HOW IT IS APPLIED
Avitene Ultrafoam	Absorbable collagen hemostat	Comes in powder; sprinkle on area
Fibrin glue Coseal Floseal Tisseal	Equal amounts of cryoprecipitate and thrombin	Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare
Gelfoam	Absorbable gelatin sponge	Cut in strips of appropriate size and apply to area
Surgicel	Oxidized regenerated cellulose	Cut in strips of appropriate size and apply to area

STEP 4Hypogastric Artery Ligation

SALLY’S CASE

Bleeding persists

Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.

If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.^7,8

 

STEP 5When All Else Fails: “Pack And Go”

If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.^10-12

A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.

For the Logothetopolous or “parachute” pack,^13,14 about 6 yards of 4-inch gauze is packed in the center of a 24-inch square laparotomy tape or a sterile bowel isolation bag, tied, and pulled through the vagina. Pressure is maintained with a weight tied to the end that is brought out through the vagina. One problem with the parachute pack is that further bleeding or injury to the bowel upon removal may not be recognized early.

SALLY’S CASE

Hemorrhage abates

A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.

She undergoes reoperation 36 hours later, at which time no bleeding is encountered.

The left ureter is reimplanted into the bladder, and she makes a full recovery.

The author has served on the speakers bureau for Wyeth.

SALLY’S CASE

Placenta accreta leads to hemorrhage

Sally is a 27-year-old gravida with 1 prior cesarean whose ultrasound imaging is suspicious for “placenta adherent to the bladder.” At 38 weeks, she delivers a viable infant by classical cesarean, at which time the ultrasound finding is confirmed: the placenta is densely adherent.

The placenta is left in situ, no methotrexate is given, and Sally is followed with clotting studies and exams.

Eight weeks later, when her fibrinogen level falls and the prothrombin time and partial thromboplastin time become abnormal, the obstetrician attempts to perform dilatation and evacuation, but massive bleeding ensues. The physician then performs a total abdominal hysterectomy, but bleeding continues from the cuff.

What is the best way to manage the hemorrhage?

After identifying its source, the surgeon should apply pressure to abate the bleeding, using packing if necessary, and repair the affected artery or vein. Fortunately, we have many tools at our disposal, from preventive steps like careful preoperative assessment to the use of hemostatic agents, fibrin glues, hypogastric artery ligation, and specialized pelvic packing techniques. With prompt action and a stepwise approach, this bona fide catastrophe can usually be successfully managed. This article details a 5-step action plan.

If massive bleeding occurs during laparoscopic or vaginal surgery, a laparotomy may be indicated, and intraoperative management would follow the same 5 steps.

STEP 1Like the Boy Scouts, Be Prepared

Although surgeons are acutely aware that drugs such as warfarin and heparin can cause intraoperative bleeding, the patient history and predisposing factors sometimes get short shrift.

Besides asking about the patient’s medications, assess the following:

• Platelets. The primary laboratory test to evaluate potential bleeding is the platelet count. In general, 10,000 to 20,000 platelets are needed for hemostasis. However, 50,000 are needed for any surgery or invasive procedure, such as insertion of a central line.¹ I recommend platelet evaluation for patients scheduled for major abdominal surgery.
  
• History of bleeding. If the patient or her family has a history of bleeding with any surgery, evaluate her for von Willebrand’s disease.
  
• High alcohol intake warrants preoperative liver function and coagulation studies.
  
• Some herbal or natural remedies can exacerbate intraoperative hemorrhage through their inhibition of coagulation, especially the agents listed in TABLE 1. They should generally be discontinued 2 to 7 days before surgery.²
  
• Aspirin and nonsteroidal anti-inflammatory drugs should be discontinued 7 days before anticipated surgery. However, patients may continue aspirin at a daily dose of 81 mg.
  
• Poor nutrition and obesity predispose the patient to wound complications and intraoperative bleeding. Patients who are severely malnourished can take dietary supplements or receive total parenteral nutrition prior to surgery.
  
• Intraoperative factors such as the 3 “inadequacies” (inadequate incision, retraction, and anesthesia), low core body temperature, severe adhesions (ie, endometriosis), and large vascular tumors also are sometimes associated with bleeding.
  

For patients predisposed to bleeding, obtaining exposure is mandatory. Blood components and a cell-saving device also should be available, as described below.

TABLE 1

Alternative remedies that may exacerbate bleeding

• 32% to 37% of Americans use these remedies, but only 38% of them tell their doctor
  
• Stop all alternative remedies 2 to 7 days before surgery
  

REMEDY	USED FOR	PERIOPERATIVE RISKS
Beta-carotene	Vitamin A precursor; often taken as a nutritional supplement	May cause coagulopathy
Feverfew	Used to prevent or treat migraine and ease menstrual cramps	May inhibit coagulation
Fish oil	Rich in omega-3 fatty acids, recommended for cardiovascular health	Omega-3s inhibit coagulation
Garlic	Used to reduce hypertension and high cholesterol	Case reports of unexpected or increased surgical bleeding, prolonged bleeding time, and impaired platelet aggregation
Ginkgo	Treatment of dementia, impaired cognition, and memory	Various ginkgolides have platelet-activating-factor antagonist properties; case reports of spontaneous bleeding
Ginseng	Widely used as a stimulant, tonic, diuretic, mood elevator, and energy booster	May cause hypertension, cardiovascular instability, coagulopathy, and sedation
St. John’s wort	Antidepressant	May cause cardiovascular instability, coagulopathy, and sedation
Vitamin E	Antioxidant	May interfere with coagulation

STEP 2Follow These Basic Principles

Whenever bleeding is encountered in any area of the abdominal cavity, the first step is simple: Apply immediate pressure with a finger or sponge stick. Then obtain exposure and assistance. Exposure usually means extending the incision and using a fixed table retractor.

 

If the source of bleeding is unknown, apply pressure on the aorta using a hand, weighted speculum, or Conn aortic compressor (Pilling-branded, Teleflex Medical, Limerick, Pa).

Secure individual vessels with finetipped clamps and small-caliber sutures or clips, and minimize the use of clamps. Never place clamps or sutures blindly, and never use electrocautery for large lacerations.

If you choose to use packs to temporarily control bleeding, insert them carefully to avoid tearing veins, and place pelvic packs (hot or cold) in a stepwise fashion, from sidewall to sidewall. Leave packs in place for at least 15 minutes and remove them sequentially.

Great vessel injuries

The aorta, vena cava, and common iliac vessels are sometimes injured during removal of paraaortic nodes or when the inferior mesenteric vessels are avulsed during retraction of the sigmoid colon. In addition, needle or trocar injuries during operative laparoscopy occur in as many as 4 of every 10,000 procedures.³

Again, the first step in managing great vessel injuries is applying pressure. Then obtain blood components, and, if necessary, consult with a vascular surgeon or gynecologic oncologist.

In general, once the patient is hemodynamically stable, the affected vessel should be compressed proximally and distally. Use Allis or vascular clamps on the torn edges to elevate the lacerated area. My preference is to close these injuries with a running 5-0 or 6-0 nylon or monofilament polypropylene (MFPP) suture on a cardiovascular needle.

Replacing blood and its components

Be aware of the following replacement guidelines for catastrophic intraoperative hemorrhage:

• For every 8 U of red blood cells replaced, give 2 U of fresh frozen plasma.
  
• If more than 10 U of red blood cells are replaced, give 10 U of platelets, preferably at the end of the procedure.
  
• With prolonged PTT, give fresh frozen plasma.
  
• If fibrinogen is low, give 2 U of cryoprecipitate.¹
  

Primary volume expansion should be performed before replacing blood or blood components. One option when facing massive hemorrhage is to give cryoprecipitate initially.

When massive bleeding is anticipated or encountered, the Haemonetics Cell Saver (Haemonetics Corp, Braintree, Mass) is invaluable. This device, which requires a trained technician, removes blood from the operative field, anticoagulates it, and washes red blood cells, which are infused. It is accepted by many Jehovah’s Witnesses,⁴ and has been used safely in women with cesarean-associated bleeding.⁵ Relative contraindications include malignancy and bacterial contamination from a ruptured abscess or inadvertent injury to unprepared bowel.⁶ The Cell Saver may be used after heavy bleeding from hysterectomy or in patients with ruptured membranes.

STEP 3Try A Topical Hemostatic Agent

If hemorrhage contiues after arterial bleeders are secured, consider a topical hemostatic agent (TABLE 2). All such agents require pressure to be applied for 3 to 5 minutes.

My preferences are Surgicel (Johnson & Johnson, New Brunswick, NJ) and Gelfoam (Pharmacia, Kalamazoo, Mich). In general, Avitene Ultrafoam collagen hemostat (Davol, subsidiary of C.R. Bard, Murray Hill, NJ) works poorly in the presence of thrombocytopenia and should be used with caution near the ureter.

Fibrin glue has been widely used as a hemostatic agent in microvascular, cardiovascular, and thoracic surgery.

To prepare fibrin glue at my institution, we use a double-barrel syringe to apply equal amounts of cryoprecipitate and thrombin at the same time. One fibrin sealant, Tisseal VH (Baxter Healthcare, Deerfield, Ill), comes with a Duploject applicator. After the agent is thoroughly applied (it is sprayed), pressure is applied for 3 to 5 minutes.

The same manufacturer also produces Coseal, which is used in vascular reconstruction to achieve additional hemostasis by mechanically sealing off areas of leakage, and Floseal, to help achieve hemostasis when ligatures or clips are impractical.

TABLE 2

Topical intraperitoneal hemostatic agents

AGENT	WHAT IT IS	HOW IT IS APPLIED
Avitene Ultrafoam	Absorbable collagen hemostat	Comes in powder; sprinkle on area
Fibrin glue Coseal Floseal Tisseal	Equal amounts of cryoprecipitate and thrombin	Spray on affected area with double-barrel syringe or device supplied by Baxter Healthcare
Gelfoam	Absorbable gelatin sponge	Cut in strips of appropriate size and apply to area
Surgicel	Oxidized regenerated cellulose	Cut in strips of appropriate size and apply to area

STEP 4Hypogastric Artery Ligation

SALLY’S CASE

Bleeding persists

Because of the hemorrhage, a gynecologic oncology consult is obtained and the hypogastric artery is ligated bilaterally, but bleeding continues. During further exploration, the left ureter is found to be ligated. Sally receives 65 U of packed red blood cells, platelets, and fresh frozen plasma. The Cell Saver also is used.

If pelvic oozing persists after application of a topical hemostatic agent, consider hypogastric artery ligation, which controls pelvic hemorrhage in as many as 50% of patients.^7,8

 

STEP 5When All Else Fails: “Pack And Go”

If intraoperative bleeding persists despite hypogastric artery ligation and the other measures, the life-saving modality of choice is a pelvic pack left in place 2 to 3 days. I prefer a fast, simple method: “pack and go” or damage-control technique.^10-12

A 2- to 4-inch Kerlix gauze (Kendall Health Care Products, Mansfield, Mass) is tightly packed over a fibrin glue bed from side to side in the pelvis. Only the skin is closed using towel clips or a running suture. The patient is immediately transferred to intensive care, where acidosis, coagulopathy, and hypothermia are corrected. In 48 to 72 hours, the packs are gently removed with saline drip assistance. If hemostasis still has not been achieved, repacking is an option.

For the Logothetopolous or “parachute” pack,^13,14 about 6 yards of 4-inch gauze is packed in the center of a 24-inch square laparotomy tape or a sterile bowel isolation bag, tied, and pulled through the vagina. Pressure is maintained with a weight tied to the end that is brought out through the vagina. One problem with the parachute pack is that further bleeding or injury to the bowel upon removal may not be recognized early.

SALLY’S CASE

Hemorrhage abates

A “pack and go” technique is used to control bleeding. The fascia is left open, and the skin is closed with towel clips over the tight pelvic pack. Sally is sent to the ICU, where clotting parameters are corrected.

She undergoes reoperation 36 hours later, at which time no bleeding is encountered.

The left ureter is reimplanted into the bladder, and she makes a full recovery.

The author has served on the speakers bureau for Wyeth.

Maria’ case

she wants laparoscopy. yes or no?

Maria is a 57-year-old mother of 4 who presents to a gynecologic oncologist with pelvic pain and ultrasonographic evidence of a 7-cm complex mass at the right adnexa. She has an enlarged fibroid uterus (12-week size), a preoperative CA125 level of 21 U/mL, and she says she wants laparoscopic management.

Is minimally invasive surgery an acceptable choice?

This large, complex mass is possibly malignant. Until now, laparoscopy has played only a small role in the management of ovarian cancer, although it has greatly changed treatment of other gynecologic malignancies. Since women with ovarian cancer tend to be older and have coexisting diseases, laparoscopy could confer many benefits, provided surgical staging is comprehensive, and timely diagnosis and patient outcomes are not compromised.¹

The utility of laparoscopy in ovarian borderline tumors and cancer is increasing. This article surveys current applications and concerns, including

• when to refer,
• predicting malignancy,
• effects of carbon dioxide (CO₂) peritoneum,
• risk of port-site recurrences,
• hand-assisted laparoscopy,
• comprehensive staging, and
• assessing resectability.

4 applications

Conventional staging by laparotomy with a vertical incision from above the umbilicus to the symphysis pubis is still the gold standard; however, laparoscopy can be used in the management of selected cases of ovarian cancer:

• to manage and stage apparent early-stage ovarian cancer,
• to determine the extent of advanced disease and potential resectability,
• to resect disease via hand-assisted laparoscopy in selected women with advanced disease, and
• to obtain a “second look,” or reassess the patient for disease recurrence and placement of intraperitoneal catheters.

Benefits of laparoscopy for benign masses

The benefits of laparoscopy over laparotomy in the management of benign adnexal masses are well defined:²

• less postoperative morbidity,
• less postoperative pain,
• less analgesia required,
• shorter hospitalizations, and
• shorter recovery time.

When to refer. Referral of at-risk patients to a gynecologic oncologist should be based on personal and family history, physical, imaging, and tumor markers.

When to get a consult: ASAP. General gynecologists may encounter malignancy unexpectedly. When they do, it is of paramount importance to obtain gynecologic oncology consultation intraoperatively, if possible, or as soon as possible postoperatively.

Predicting Malignancy

How common is cancer in laparoscopically managed masses?

Consider a complex ovarian mass potentially malignant until proven otherwise. Why? Because it remains difficult to rule out malignancy preoperatively, even with strict patient selection.

For example, a study involving 292 laparoscopically managed women found a 3.8% malignancy rate.³ These women had undergone preoperative vaginal ultrasound, CA125 measurement, and pelvic examination, but malignancy was not detected until surgery.

The incidence of malignancy at laparoscopy for a pelvic mass varies widely due to different guidelines for patient selection. In 1 series of 757 patients,⁴ the rate of unanticipated malignancy was 2.5%. This included 7 invasive cancers and 12 borderline tumors. Preoperative evaluation entailed routine clinical and ultrasound examinations. At laparoscopy, peritoneal cytology was obtained, the ovaries and peritoneum were inspected, and any cysts were punctured so their contents could be examined. If a malignant mass was encountered or suspected, the woman in question was treated by immediate laparotomy using a vertical midline incision.⁴

History of nongynecologic cancer heightens risk of malignancy

For example, of 31 women with stage IV breast cancer and a new adnexal mass, 3 (10%) were found to have primary ovarian cancer, and 21 (68%) had metastatic breast cancer.⁵

In a study at our institution,⁶ 51 of 264 patients (19%) with a history of nongynecologic cancer and a new adnexal mass were found to have a malignancy. Of these women, 22 (43%) had primary ovarian cancer; the rest had metastatic disease. Most patients had laparoscopy even when malignancy was encountered.

Utility of frozen section

Frozen-section analysis speeds diagnosis of the adnexal mass, allowing the necessary surgery to be performed immediately.The overall accuracy of frozen-section analysis is high, reported at 92.7% in 1 study.⁷ It is less accurate in borderline tumors because of the extensive sampling required.

 

Intraoperative frozen section has high accuracy in women with metastases to the adnexae. In 36 patients with a history of breast or colorectal carcinoma who developed adnexal metastases, intraoperative frozen section correctly diagnosed carcinoma in 35 patients (97%). In more than 80% of these women, the carcinoma was accurately diagnosed as metastatic.⁸

Laparoscopy for Suspicious Masses?

Is laparoscopy appropriate for pelvic masses that appear suspicious for cancer at the time of preoperative evaluation? And if malignancy is confirmed, is conversion to laparotomy warranted?

Advocates of laparoscopy as the initial diagnostic tool say yes to the first question, pointing to the fact that most suspicious masses are later found to be benign.^9,10

For example, Dottino et al¹⁰ managed all pelvic masses referred to their oncology unit laparoscopically unless there was evidence of gross metastatic disease (ie, omental cake) or the mass extended above the umbilicus. Immediate frozen-section analysis was performed in all cases. Although most of the masses were suspicious for malignancy preoperatively, 87% were in fact benign, and 88% were successfully managed by laparoscopy. If conversion to laparotomy was necessary for successful debulking, it was performed. However, laparoscopic surgery often was adequate.

Canis and colleagues⁹ support diagnostic laparoscopy regardless of the ultrasonographic appearance of the pelvic mass, although they recommend immediate conversion to laparotomy for staging if malignancy is found.

Does CO₂ Sspread Cancer?

Whether CO₂ contributes to cancer spread and growth is of particular concern in ovarian cancer, since it is predominantly a peritoneal disease. In a rat ovarian cancer model, tumor dissemination increased throughout the peritoneal cavity with laparoscopy, compared with laparotomy, without increased tumor growth.¹¹

However, a separate study¹² in women with persistent metastatic intraabdominal peritoneal or ovarian cancer at the time of second-look surgery found no difference in overall survival between patients who had undergone laparoscopy versus laparotomy

Fear of Port-Site Recurrence

Fear of tumor implantation at the trocar site is commonly cited as a reason to avoid laparoscopy in ovarian cancer. One metaanalysis found a port-site recurrence rate of 1.1% to 13.5%, but many of the studies included were small series or case reports.¹³ In ovarian cancer, most reports of port-site recurrences have been associated with advanced-stage disease with peritoneal seeding and the presence of ascites.^13,14

The term “port-site recurrence” (previously it was thought to be a metastasis) describes cancer occurring in the subcutis in the absence of carcinomatosis.¹⁵ Now that the definition has been refined, the rate of port-site recurrences may be substantially lower.

A large retrospective study at our institution found 4 (0.64%) subcutaneous tumor implantations at or near a trocar site after 625 laparoscopic procedures in 584 women with ovarian/tubal cancer. Most of these implantations were discovered after positive second-look operations, and all were associated with synchronous carcinomatosis or other sites of metastatic disease.¹⁶

In a separate study¹⁴ involving 102 women with primary or recurrent advanced-stage ovarian cancer, large-volume ascites and a longer interval between chemotherapy and cytoreductive surgery were associated with more port-site recurrences. In addition, full-layer closure of the abdominal wall reduced port-site recurrences from 58% to 2%, emphasizing the importance of trocar-site closure in cases of malignancy. There was no survival disadvantage in women with portsite recurrences.

What causes port-site recurrences?

Possible factors include:

• trauma to the site,
• frequent removal of instruments through the port,
• removing the specimen through the port, and
• continued leakage of ascites.¹³

Avoiding cyst spillage and routinely using laparoscopic bags for cyst removal may decrease the incidence of these recurrences (FIGURE 1). Partial cyst excision and morcellation of a solid mass are always contraindicated.

Irrigation of port sites may decrease tumor cell implantation and should be considered at the end of the procedure.¹³ To further reduce risk, experts recommend closing all layers at the time of laparoscopy and resecting laparoscopic ports in their full thickness at the time of the staging laparotomy.¹⁴

FIGURE 1 Cyst removal using an endoscopic bag

Avoid spillage and routinely use laparoscopic bags for cyst removal to decrease the incidence of port-site recurrences.

Hand-Assisted Laparoscopy

This hybrid procedure combines the advantages of minimally invasive surgery with the tactile sensation of laparotomy. It has gained favor among urologists and general surgeons. (The first nephrectomy using this method was performed in 1996.¹⁷)

Technological advances now enable the surgeon to insert and remove the nondominant hand into the peritoneal cavity without losing pneumoperitoneum and to insert instruments through the same port if needed (FIGURE 2).

Advantages over traditional laparoscopy include the ability to palpate tissue, assist with tissue retraction, perform blunt dissection, and rapidly control hemostasis. This approach has been described in management and staging of early-stage ovarian cancer and in debulking advanced disease.¹⁸

 

FIGURE 2 Hand-assisted laparoscopy

The nondominant hand and surgical instruments can be inserted and removed through the special port without affecting pneumoperitoneum.

Surgical Staging

Maria’ case

resection and analysis of ovary

Maria underwent laparoscopy via the open technique. The surgeon found a cystic right ovarian mass, a fibroid uterus, and small diaphragmatic nodules, which were biopsied and found to be benign.

Pelvic washings were obtained, and after the right infundibular pelvic ligament and right utero-ovarian ligament were clamped and cut, the intact ovary was placed in a laparoscopic bag. The bag was pulled through the 12-mm suprapubic trocar, the cyst wall was perforated, and the cyst was drained within the laparoscopic bag, producing brown fluid. The bag was removed from the peritoneal cavity through this port, and the cyst was sent to pathology.

There was no contamination to the peritoneal cavity or abdominal wall, and the bag remained intact. Surgical gloves were then changed, and instruments used to drain the cyst were removed from the operating field.

When frozen-section analysis revealed a borderline serous ovarian tumor, Maria underwent BSO, infracolic omentectomy, laparoscopic pelvic and paraaortic lymphadenectomy, and laparoscopically assisted vaginal hysterectomy. There were no intraoperative complications, the total time in the operating room was 330 minutes, and there was blood loss of approximately 150 mL.

When an ovarian malignancy is discovered, immediate staging is indicated, and should include:

• peritoneal biopsies,
• pelvic and para-aortic lymph node sampling,
• infracolic omentectomy, and
• bilateral salpingo-oophorectomy (BSO) and hysterectomy.¹

With presumed stage I disease, there is a 20% to 30% likelihood of upstaging after comprehensive surgical staging, with disease often discovered in the lymph nodes.^19,20

Since changes in staging affect prognosis and treatment, complete staging should include the retroperitoneal nodes.

When the patient wants to preserve fertility

In selected younger women who have not yet completed childbearing, conservative treatment with retention of the uterus and contralateral ovary is an option—though we lack outcomes data on patients treated this way.

This option should be restricted to women with proven stage I disease after comprehensive staging.¹

Can staging be done laparoscopically?

Complete staging—consisting of a detailed peritoneal assessment (with BSO and vaginal hysterectomy), omentectomy, and pelvic and para-aortic node dissection—can safely be done laparoscopically.^19-21 Studies show low morbidity, with accurate findings and adequate node counts.^21,22

A comparison of laparoscopic and conventional (laparotomy) staging in women with apparent stage I adnexal cancers found no differences in omental specimen size or the number of lymph nodes removed, and none of the patients required conversion to laparotomy.²²

When definitive staging is delayed

Several studies have found poorer outcomes with delayed staging. However, the tumor ruptured in some of these studies, with considerable delay from the initial laparoscopy until definitive staging and treatment.

To increase the likelihood of an accurate stage, gather as much information as possible on the extent of disease: Describe the intraoperative findings and inspect the abdomen and pelvis thoroughly at initial surgery if a skilled oncologic surgeon is not immediately available. Then make every effort to schedule a complete staging procedure as soon as possible, as some consider this an “oncologic emergency.”⁹

Whether and when to stage LMP tumors

Preoperative prediction and intraoperative diagnosis of low malignant potential (LMP) tumors is challenging. If such a tumor is confirmed by frozen section, the usual treatment is unilateral salpingo-oophorectomy. When the patient is postmenopausal or has completed childbearing, BSO, hysterectomy, and staging should be considered.¹

Surgical staging should be performed at the initial surgery, if at all possible. However, if final pathology confirms an LMP tumor and disease appears to be confined to the adnexa, repeat surgery for staging is controversial because of the limited data on its benefit, particularly in regard to mucinous borderline tumors.

Restaging may be more useful in selected cases of serous LMP tumors with histologic micropapillary features, since these tumors may be associated with a higher incidence of invasive implants (eg, in the omentum or peritoneum) that may require chemotherapy.

If a malignant cyst ruptures, does it affect staging?

The effect of intraoperative tumor spillage in stage I disease is debatable, although ascites and preoperative rupture are associated with a poorer prognosis.²³

Even though a number of investigators (TABLE) have found intraoperative spillage to have no adverse impact on survival, make every effort to maintain capsular integrity to minimize any possibility of peritoneal tumor dissemination.

In some cases, intraoperative cyst rupture warrants upstaging from International Federation of Gynecology and Obstetrics (FIGO) stage IA to 1C, necessitating adjuvant chemotherapy when it otherwise would not have been required.¹

 

Cyst rupture is no more likely with laparoscopy than with laparotomy,² and is unrelated to the surgical route. It is more closely associated with the frequency of cystectomy.²⁴

If rupture does occur, thoroughly irrigate the peritoneal cavity.

TABLE

When a cyst ruptures during surgery, what is the prognosis? The data are mixed on the significance of this event in stage I ovarian cancer

AUTHOR	NUMBER OF CASES	IMPACT
Sevelda 1990 (Austria)	204	No prognostic importance
Sainz 1994 (US)	79	May worsen prognosis
Sjovall 1994 (Sweden)	394	No negative influence
Ahmed 1996 (UK)	194	Not prognostically significant
Vergote 2001 (Belgium)	1,545	Rupture should be avoided (hazard ratio = 1.64)

How chemotherapy comes into play

If final pathology shows stage IC or high-grade histology, chemotherapy generally is offered to women managed in the United States. In selected cases, chemotherapy is given immediately after the initial surgery if completing a full staging procedure would considerably delay chemotherapy.

Leblanc et al²¹ found that, when staging was performed after completion of chemotherapy in women with stage IC or high-grade histology, 3 of 11 patients (27%) had positive nodes. Because positive nodes can be less chemosensitive, Leblanc and colleagues advocate either of 2 options: immediate restaging, including retroperitoneal nodes, or staging after chemotherapy, including retroperitoneal nodes.

Advanced Ovarian Cancer

Optimal surgical cytoreduction by laparotomy, followed by platinum-based chemotherapy, maximizes survival in women with advanced ovarian cancer. Unfortunately, in many patients, optimal debulking is not feasible, and laparotomy without optimal cytoreduction offers no survival advantage.²⁵ At the same time, preoperative imaging has limited ability to determine the feasibility of cytoreduction. For example, computed tomography is highly sensitive when it comes to detecting ascites and mesenteric and omental disease (FIGURE 3), but is not as successful in detecting gallbladder fossa disease and diffuse peritoneal nodules smaller than 2 cm.

As a result, laparoscopy is increasingly used to determine whether optimal resection is feasible. If it is, immediate laparotomy is appropriate. Otherwise, a tissue specimen is obtained for histological confirmation, allowing accurate diagnosis prior to chemotherapy.

FIGURE 3 Omental cake signifies metastasis

Omental cake in a stage IIIC ovarian cancer patient. Disease appears to be resectable.

Potential drawbacks of laparoscopy

In selected women with advanced cancer, laparoscopy may be a good way to determine which patients would not benefit from laparotomy, thus sparing them the morbidity of an additional operation. But laparoscopy can have limitations:

• Ascites can reduce visibility.
• Omental and bowel adhesion to the anterior abdominal wall may increase the likelihood of bowel injury.
• Trocar site implantation may increase in the presence of adenocarcinoma, ascites, and carcinomatosis.¹³

If trocar sites are carefully closed and chemotherapy is initiated promptly, these risks can be substantially reduced.¹⁴

 

Second-Look Laparoscopy

Second-look surgery in women with a complete clinical response (normal exam, imaging, and CA125) after primary chemotherapy is controversial. This surgery aims to identify women with pathologically negative or microscopic disease who may benefit from consolidation therapy, or with larger-volume disease who can undergo secondary cytoreduction.²⁷ Laparoscopy meets these goals safely with comparable accuracy and less morbidity than laparotomy.^12,27

Maria’ case

lmp tumor and negative nodes

Maria did well postoperatively and went home on day 4. Her final pathology report: a right papillary serous adenocarcinoma of LMP (borderline) with small (<1 mm) foci of microinvasion. She had 6 negative paraaortic nodes, 19 negative pelvic nodes, negative pelvic washings and omentum, a normal left ovary, and a 6-cm cellular leiomyoma in an otherwise normal uterus.

She required no adjuvant treatment and is now 22 months postoperative without evidence of disease.

The authors report no financial relationships relevant to this article.

Maria’ case

she wants laparoscopy. yes or no?

Maria is a 57-year-old mother of 4 who presents to a gynecologic oncologist with pelvic pain and ultrasonographic evidence of a 7-cm complex mass at the right adnexa. She has an enlarged fibroid uterus (12-week size), a preoperative CA125 level of 21 U/mL, and she says she wants laparoscopic management.

Is minimally invasive surgery an acceptable choice?

This large, complex mass is possibly malignant. Until now, laparoscopy has played only a small role in the management of ovarian cancer, although it has greatly changed treatment of other gynecologic malignancies. Since women with ovarian cancer tend to be older and have coexisting diseases, laparoscopy could confer many benefits, provided surgical staging is comprehensive, and timely diagnosis and patient outcomes are not compromised.¹

The utility of laparoscopy in ovarian borderline tumors and cancer is increasing. This article surveys current applications and concerns, including

• when to refer,
• predicting malignancy,
• effects of carbon dioxide (CO₂) peritoneum,
• risk of port-site recurrences,
• hand-assisted laparoscopy,
• comprehensive staging, and
• assessing resectability.

4 applications

Conventional staging by laparotomy with a vertical incision from above the umbilicus to the symphysis pubis is still the gold standard; however, laparoscopy can be used in the management of selected cases of ovarian cancer:

• to manage and stage apparent early-stage ovarian cancer,
• to determine the extent of advanced disease and potential resectability,
• to resect disease via hand-assisted laparoscopy in selected women with advanced disease, and
• to obtain a “second look,” or reassess the patient for disease recurrence and placement of intraperitoneal catheters.

Benefits of laparoscopy for benign masses

The benefits of laparoscopy over laparotomy in the management of benign adnexal masses are well defined:²

• less postoperative morbidity,
• less postoperative pain,
• less analgesia required,
• shorter hospitalizations, and
• shorter recovery time.

When to refer. Referral of at-risk patients to a gynecologic oncologist should be based on personal and family history, physical, imaging, and tumor markers.

When to get a consult: ASAP. General gynecologists may encounter malignancy unexpectedly. When they do, it is of paramount importance to obtain gynecologic oncology consultation intraoperatively, if possible, or as soon as possible postoperatively.

Predicting Malignancy

How common is cancer in laparoscopically managed masses?

Consider a complex ovarian mass potentially malignant until proven otherwise. Why? Because it remains difficult to rule out malignancy preoperatively, even with strict patient selection.

For example, a study involving 292 laparoscopically managed women found a 3.8% malignancy rate.³ These women had undergone preoperative vaginal ultrasound, CA125 measurement, and pelvic examination, but malignancy was not detected until surgery.

The incidence of malignancy at laparoscopy for a pelvic mass varies widely due to different guidelines for patient selection. In 1 series of 757 patients,⁴ the rate of unanticipated malignancy was 2.5%. This included 7 invasive cancers and 12 borderline tumors. Preoperative evaluation entailed routine clinical and ultrasound examinations. At laparoscopy, peritoneal cytology was obtained, the ovaries and peritoneum were inspected, and any cysts were punctured so their contents could be examined. If a malignant mass was encountered or suspected, the woman in question was treated by immediate laparotomy using a vertical midline incision.⁴

History of nongynecologic cancer heightens risk of malignancy

For example, of 31 women with stage IV breast cancer and a new adnexal mass, 3 (10%) were found to have primary ovarian cancer, and 21 (68%) had metastatic breast cancer.⁵

In a study at our institution,⁶ 51 of 264 patients (19%) with a history of nongynecologic cancer and a new adnexal mass were found to have a malignancy. Of these women, 22 (43%) had primary ovarian cancer; the rest had metastatic disease. Most patients had laparoscopy even when malignancy was encountered.

Utility of frozen section

Frozen-section analysis speeds diagnosis of the adnexal mass, allowing the necessary surgery to be performed immediately.The overall accuracy of frozen-section analysis is high, reported at 92.7% in 1 study.⁷ It is less accurate in borderline tumors because of the extensive sampling required.

 

Intraoperative frozen section has high accuracy in women with metastases to the adnexae. In 36 patients with a history of breast or colorectal carcinoma who developed adnexal metastases, intraoperative frozen section correctly diagnosed carcinoma in 35 patients (97%). In more than 80% of these women, the carcinoma was accurately diagnosed as metastatic.⁸

Laparoscopy for Suspicious Masses?

Is laparoscopy appropriate for pelvic masses that appear suspicious for cancer at the time of preoperative evaluation? And if malignancy is confirmed, is conversion to laparotomy warranted?

Advocates of laparoscopy as the initial diagnostic tool say yes to the first question, pointing to the fact that most suspicious masses are later found to be benign.^9,10

For example, Dottino et al¹⁰ managed all pelvic masses referred to their oncology unit laparoscopically unless there was evidence of gross metastatic disease (ie, omental cake) or the mass extended above the umbilicus. Immediate frozen-section analysis was performed in all cases. Although most of the masses were suspicious for malignancy preoperatively, 87% were in fact benign, and 88% were successfully managed by laparoscopy. If conversion to laparotomy was necessary for successful debulking, it was performed. However, laparoscopic surgery often was adequate.

Canis and colleagues⁹ support diagnostic laparoscopy regardless of the ultrasonographic appearance of the pelvic mass, although they recommend immediate conversion to laparotomy for staging if malignancy is found.

Does CO₂ Sspread Cancer?

Whether CO₂ contributes to cancer spread and growth is of particular concern in ovarian cancer, since it is predominantly a peritoneal disease. In a rat ovarian cancer model, tumor dissemination increased throughout the peritoneal cavity with laparoscopy, compared with laparotomy, without increased tumor growth.¹¹

However, a separate study¹² in women with persistent metastatic intraabdominal peritoneal or ovarian cancer at the time of second-look surgery found no difference in overall survival between patients who had undergone laparoscopy versus laparotomy

Fear of Port-Site Recurrence

Fear of tumor implantation at the trocar site is commonly cited as a reason to avoid laparoscopy in ovarian cancer. One metaanalysis found a port-site recurrence rate of 1.1% to 13.5%, but many of the studies included were small series or case reports.¹³ In ovarian cancer, most reports of port-site recurrences have been associated with advanced-stage disease with peritoneal seeding and the presence of ascites.^13,14

The term “port-site recurrence” (previously it was thought to be a metastasis) describes cancer occurring in the subcutis in the absence of carcinomatosis.¹⁵ Now that the definition has been refined, the rate of port-site recurrences may be substantially lower.

A large retrospective study at our institution found 4 (0.64%) subcutaneous tumor implantations at or near a trocar site after 625 laparoscopic procedures in 584 women with ovarian/tubal cancer. Most of these implantations were discovered after positive second-look operations, and all were associated with synchronous carcinomatosis or other sites of metastatic disease.¹⁶

In a separate study¹⁴ involving 102 women with primary or recurrent advanced-stage ovarian cancer, large-volume ascites and a longer interval between chemotherapy and cytoreductive surgery were associated with more port-site recurrences. In addition, full-layer closure of the abdominal wall reduced port-site recurrences from 58% to 2%, emphasizing the importance of trocar-site closure in cases of malignancy. There was no survival disadvantage in women with portsite recurrences.

What causes port-site recurrences?

Possible factors include:

• trauma to the site,
• frequent removal of instruments through the port,
• removing the specimen through the port, and
• continued leakage of ascites.¹³

Avoiding cyst spillage and routinely using laparoscopic bags for cyst removal may decrease the incidence of these recurrences (FIGURE 1). Partial cyst excision and morcellation of a solid mass are always contraindicated.

Irrigation of port sites may decrease tumor cell implantation and should be considered at the end of the procedure.¹³ To further reduce risk, experts recommend closing all layers at the time of laparoscopy and resecting laparoscopic ports in their full thickness at the time of the staging laparotomy.¹⁴

FIGURE 1 Cyst removal using an endoscopic bag

Avoid spillage and routinely use laparoscopic bags for cyst removal to decrease the incidence of port-site recurrences.

Hand-Assisted Laparoscopy

This hybrid procedure combines the advantages of minimally invasive surgery with the tactile sensation of laparotomy. It has gained favor among urologists and general surgeons. (The first nephrectomy using this method was performed in 1996.¹⁷)

Technological advances now enable the surgeon to insert and remove the nondominant hand into the peritoneal cavity without losing pneumoperitoneum and to insert instruments through the same port if needed (FIGURE 2).

Advantages over traditional laparoscopy include the ability to palpate tissue, assist with tissue retraction, perform blunt dissection, and rapidly control hemostasis. This approach has been described in management and staging of early-stage ovarian cancer and in debulking advanced disease.¹⁸

 

FIGURE 2 Hand-assisted laparoscopy

The nondominant hand and surgical instruments can be inserted and removed through the special port without affecting pneumoperitoneum.

Surgical Staging

Maria’ case

resection and analysis of ovary

Maria underwent laparoscopy via the open technique. The surgeon found a cystic right ovarian mass, a fibroid uterus, and small diaphragmatic nodules, which were biopsied and found to be benign.

Pelvic washings were obtained, and after the right infundibular pelvic ligament and right utero-ovarian ligament were clamped and cut, the intact ovary was placed in a laparoscopic bag. The bag was pulled through the 12-mm suprapubic trocar, the cyst wall was perforated, and the cyst was drained within the laparoscopic bag, producing brown fluid. The bag was removed from the peritoneal cavity through this port, and the cyst was sent to pathology.

There was no contamination to the peritoneal cavity or abdominal wall, and the bag remained intact. Surgical gloves were then changed, and instruments used to drain the cyst were removed from the operating field.

When frozen-section analysis revealed a borderline serous ovarian tumor, Maria underwent BSO, infracolic omentectomy, laparoscopic pelvic and paraaortic lymphadenectomy, and laparoscopically assisted vaginal hysterectomy. There were no intraoperative complications, the total time in the operating room was 330 minutes, and there was blood loss of approximately 150 mL.

When an ovarian malignancy is discovered, immediate staging is indicated, and should include:

• peritoneal biopsies,
• pelvic and para-aortic lymph node sampling,
• infracolic omentectomy, and
• bilateral salpingo-oophorectomy (BSO) and hysterectomy.¹

With presumed stage I disease, there is a 20% to 30% likelihood of upstaging after comprehensive surgical staging, with disease often discovered in the lymph nodes.^19,20

Since changes in staging affect prognosis and treatment, complete staging should include the retroperitoneal nodes.

When the patient wants to preserve fertility

In selected younger women who have not yet completed childbearing, conservative treatment with retention of the uterus and contralateral ovary is an option—though we lack outcomes data on patients treated this way.

This option should be restricted to women with proven stage I disease after comprehensive staging.¹

Can staging be done laparoscopically?

Complete staging—consisting of a detailed peritoneal assessment (with BSO and vaginal hysterectomy), omentectomy, and pelvic and para-aortic node dissection—can safely be done laparoscopically.^19-21 Studies show low morbidity, with accurate findings and adequate node counts.^21,22

A comparison of laparoscopic and conventional (laparotomy) staging in women with apparent stage I adnexal cancers found no differences in omental specimen size or the number of lymph nodes removed, and none of the patients required conversion to laparotomy.²²

When definitive staging is delayed

Several studies have found poorer outcomes with delayed staging. However, the tumor ruptured in some of these studies, with considerable delay from the initial laparoscopy until definitive staging and treatment.

To increase the likelihood of an accurate stage, gather as much information as possible on the extent of disease: Describe the intraoperative findings and inspect the abdomen and pelvis thoroughly at initial surgery if a skilled oncologic surgeon is not immediately available. Then make every effort to schedule a complete staging procedure as soon as possible, as some consider this an “oncologic emergency.”⁹

Whether and when to stage LMP tumors

Preoperative prediction and intraoperative diagnosis of low malignant potential (LMP) tumors is challenging. If such a tumor is confirmed by frozen section, the usual treatment is unilateral salpingo-oophorectomy. When the patient is postmenopausal or has completed childbearing, BSO, hysterectomy, and staging should be considered.¹

Surgical staging should be performed at the initial surgery, if at all possible. However, if final pathology confirms an LMP tumor and disease appears to be confined to the adnexa, repeat surgery for staging is controversial because of the limited data on its benefit, particularly in regard to mucinous borderline tumors.

Restaging may be more useful in selected cases of serous LMP tumors with histologic micropapillary features, since these tumors may be associated with a higher incidence of invasive implants (eg, in the omentum or peritoneum) that may require chemotherapy.

If a malignant cyst ruptures, does it affect staging?

The effect of intraoperative tumor spillage in stage I disease is debatable, although ascites and preoperative rupture are associated with a poorer prognosis.²³

Even though a number of investigators (TABLE) have found intraoperative spillage to have no adverse impact on survival, make every effort to maintain capsular integrity to minimize any possibility of peritoneal tumor dissemination.

In some cases, intraoperative cyst rupture warrants upstaging from International Federation of Gynecology and Obstetrics (FIGO) stage IA to 1C, necessitating adjuvant chemotherapy when it otherwise would not have been required.¹

 

Cyst rupture is no more likely with laparoscopy than with laparotomy,² and is unrelated to the surgical route. It is more closely associated with the frequency of cystectomy.²⁴

If rupture does occur, thoroughly irrigate the peritoneal cavity.

TABLE

When a cyst ruptures during surgery, what is the prognosis? The data are mixed on the significance of this event in stage I ovarian cancer

AUTHOR	NUMBER OF CASES	IMPACT
Sevelda 1990 (Austria)	204	No prognostic importance
Sainz 1994 (US)	79	May worsen prognosis
Sjovall 1994 (Sweden)	394	No negative influence
Ahmed 1996 (UK)	194	Not prognostically significant
Vergote 2001 (Belgium)	1,545	Rupture should be avoided (hazard ratio = 1.64)

How chemotherapy comes into play

If final pathology shows stage IC or high-grade histology, chemotherapy generally is offered to women managed in the United States. In selected cases, chemotherapy is given immediately after the initial surgery if completing a full staging procedure would considerably delay chemotherapy.

Leblanc et al²¹ found that, when staging was performed after completion of chemotherapy in women with stage IC or high-grade histology, 3 of 11 patients (27%) had positive nodes. Because positive nodes can be less chemosensitive, Leblanc and colleagues advocate either of 2 options: immediate restaging, including retroperitoneal nodes, or staging after chemotherapy, including retroperitoneal nodes.

Advanced Ovarian Cancer

Optimal surgical cytoreduction by laparotomy, followed by platinum-based chemotherapy, maximizes survival in women with advanced ovarian cancer. Unfortunately, in many patients, optimal debulking is not feasible, and laparotomy without optimal cytoreduction offers no survival advantage.²⁵ At the same time, preoperative imaging has limited ability to determine the feasibility of cytoreduction. For example, computed tomography is highly sensitive when it comes to detecting ascites and mesenteric and omental disease (FIGURE 3), but is not as successful in detecting gallbladder fossa disease and diffuse peritoneal nodules smaller than 2 cm.

As a result, laparoscopy is increasingly used to determine whether optimal resection is feasible. If it is, immediate laparotomy is appropriate. Otherwise, a tissue specimen is obtained for histological confirmation, allowing accurate diagnosis prior to chemotherapy.

FIGURE 3 Omental cake signifies metastasis

Omental cake in a stage IIIC ovarian cancer patient. Disease appears to be resectable.

Potential drawbacks of laparoscopy

In selected women with advanced cancer, laparoscopy may be a good way to determine which patients would not benefit from laparotomy, thus sparing them the morbidity of an additional operation. But laparoscopy can have limitations:

• Ascites can reduce visibility.
• Omental and bowel adhesion to the anterior abdominal wall may increase the likelihood of bowel injury.
• Trocar site implantation may increase in the presence of adenocarcinoma, ascites, and carcinomatosis.¹³

If trocar sites are carefully closed and chemotherapy is initiated promptly, these risks can be substantially reduced.¹⁴

 

Second-Look Laparoscopy

Second-look surgery in women with a complete clinical response (normal exam, imaging, and CA125) after primary chemotherapy is controversial. This surgery aims to identify women with pathologically negative or microscopic disease who may benefit from consolidation therapy, or with larger-volume disease who can undergo secondary cytoreduction.²⁷ Laparoscopy meets these goals safely with comparable accuracy and less morbidity than laparotomy.^12,27

Maria’ case

lmp tumor and negative nodes

Maria did well postoperatively and went home on day 4. Her final pathology report: a right papillary serous adenocarcinoma of LMP (borderline) with small (<1 mm) foci of microinvasion. She had 6 negative paraaortic nodes, 19 negative pelvic nodes, negative pelvic washings and omentum, a normal left ovary, and a 6-cm cellular leiomyoma in an otherwise normal uterus.

She required no adjuvant treatment and is now 22 months postoperative without evidence of disease.

The authors report no financial relationships relevant to this article.

Maria’ case

she wants laparoscopy. yes or no?

Maria is a 57-year-old mother of 4 who presents to a gynecologic oncologist with pelvic pain and ultrasonographic evidence of a 7-cm complex mass at the right adnexa. She has an enlarged fibroid uterus (12-week size), a preoperative CA125 level of 21 U/mL, and she says she wants laparoscopic management.

Is minimally invasive surgery an acceptable choice?

This large, complex mass is possibly malignant. Until now, laparoscopy has played only a small role in the management of ovarian cancer, although it has greatly changed treatment of other gynecologic malignancies. Since women with ovarian cancer tend to be older and have coexisting diseases, laparoscopy could confer many benefits, provided surgical staging is comprehensive, and timely diagnosis and patient outcomes are not compromised.¹

The utility of laparoscopy in ovarian borderline tumors and cancer is increasing. This article surveys current applications and concerns, including

• when to refer,
• predicting malignancy,
• effects of carbon dioxide (CO₂) peritoneum,
• risk of port-site recurrences,
• hand-assisted laparoscopy,
• comprehensive staging, and
• assessing resectability.

4 applications

Conventional staging by laparotomy with a vertical incision from above the umbilicus to the symphysis pubis is still the gold standard; however, laparoscopy can be used in the management of selected cases of ovarian cancer:

• to manage and stage apparent early-stage ovarian cancer,
• to determine the extent of advanced disease and potential resectability,
• to resect disease via hand-assisted laparoscopy in selected women with advanced disease, and
• to obtain a “second look,” or reassess the patient for disease recurrence and placement of intraperitoneal catheters.

Benefits of laparoscopy for benign masses

The benefits of laparoscopy over laparotomy in the management of benign adnexal masses are well defined:²

• less postoperative morbidity,
• less postoperative pain,
• less analgesia required,
• shorter hospitalizations, and
• shorter recovery time.

When to refer. Referral of at-risk patients to a gynecologic oncologist should be based on personal and family history, physical, imaging, and tumor markers.

When to get a consult: ASAP. General gynecologists may encounter malignancy unexpectedly. When they do, it is of paramount importance to obtain gynecologic oncology consultation intraoperatively, if possible, or as soon as possible postoperatively.

Predicting Malignancy

How common is cancer in laparoscopically managed masses?

Consider a complex ovarian mass potentially malignant until proven otherwise. Why? Because it remains difficult to rule out malignancy preoperatively, even with strict patient selection.

For example, a study involving 292 laparoscopically managed women found a 3.8% malignancy rate.³ These women had undergone preoperative vaginal ultrasound, CA125 measurement, and pelvic examination, but malignancy was not detected until surgery.

The incidence of malignancy at laparoscopy for a pelvic mass varies widely due to different guidelines for patient selection. In 1 series of 757 patients,⁴ the rate of unanticipated malignancy was 2.5%. This included 7 invasive cancers and 12 borderline tumors. Preoperative evaluation entailed routine clinical and ultrasound examinations. At laparoscopy, peritoneal cytology was obtained, the ovaries and peritoneum were inspected, and any cysts were punctured so their contents could be examined. If a malignant mass was encountered or suspected, the woman in question was treated by immediate laparotomy using a vertical midline incision.⁴

History of nongynecologic cancer heightens risk of malignancy

For example, of 31 women with stage IV breast cancer and a new adnexal mass, 3 (10%) were found to have primary ovarian cancer, and 21 (68%) had metastatic breast cancer.⁵

In a study at our institution,⁶ 51 of 264 patients (19%) with a history of nongynecologic cancer and a new adnexal mass were found to have a malignancy. Of these women, 22 (43%) had primary ovarian cancer; the rest had metastatic disease. Most patients had laparoscopy even when malignancy was encountered.

Utility of frozen section

Frozen-section analysis speeds diagnosis of the adnexal mass, allowing the necessary surgery to be performed immediately.The overall accuracy of frozen-section analysis is high, reported at 92.7% in 1 study.⁷ It is less accurate in borderline tumors because of the extensive sampling required.

 

Intraoperative frozen section has high accuracy in women with metastases to the adnexae. In 36 patients with a history of breast or colorectal carcinoma who developed adnexal metastases, intraoperative frozen section correctly diagnosed carcinoma in 35 patients (97%). In more than 80% of these women, the carcinoma was accurately diagnosed as metastatic.⁸

Laparoscopy for Suspicious Masses?

Is laparoscopy appropriate for pelvic masses that appear suspicious for cancer at the time of preoperative evaluation? And if malignancy is confirmed, is conversion to laparotomy warranted?

Advocates of laparoscopy as the initial diagnostic tool say yes to the first question, pointing to the fact that most suspicious masses are later found to be benign.^9,10

For example, Dottino et al¹⁰ managed all pelvic masses referred to their oncology unit laparoscopically unless there was evidence of gross metastatic disease (ie, omental cake) or the mass extended above the umbilicus. Immediate frozen-section analysis was performed in all cases. Although most of the masses were suspicious for malignancy preoperatively, 87% were in fact benign, and 88% were successfully managed by laparoscopy. If conversion to laparotomy was necessary for successful debulking, it was performed. However, laparoscopic surgery often was adequate.

Canis and colleagues⁹ support diagnostic laparoscopy regardless of the ultrasonographic appearance of the pelvic mass, although they recommend immediate conversion to laparotomy for staging if malignancy is found.

Does CO₂ Sspread Cancer?

Whether CO₂ contributes to cancer spread and growth is of particular concern in ovarian cancer, since it is predominantly a peritoneal disease. In a rat ovarian cancer model, tumor dissemination increased throughout the peritoneal cavity with laparoscopy, compared with laparotomy, without increased tumor growth.¹¹

However, a separate study¹² in women with persistent metastatic intraabdominal peritoneal or ovarian cancer at the time of second-look surgery found no difference in overall survival between patients who had undergone laparoscopy versus laparotomy

Fear of Port-Site Recurrence

Fear of tumor implantation at the trocar site is commonly cited as a reason to avoid laparoscopy in ovarian cancer. One metaanalysis found a port-site recurrence rate of 1.1% to 13.5%, but many of the studies included were small series or case reports.¹³ In ovarian cancer, most reports of port-site recurrences have been associated with advanced-stage disease with peritoneal seeding and the presence of ascites.^13,14

The term “port-site recurrence” (previously it was thought to be a metastasis) describes cancer occurring in the subcutis in the absence of carcinomatosis.¹⁵ Now that the definition has been refined, the rate of port-site recurrences may be substantially lower.

A large retrospective study at our institution found 4 (0.64%) subcutaneous tumor implantations at or near a trocar site after 625 laparoscopic procedures in 584 women with ovarian/tubal cancer. Most of these implantations were discovered after positive second-look operations, and all were associated with synchronous carcinomatosis or other sites of metastatic disease.¹⁶

In a separate study¹⁴ involving 102 women with primary or recurrent advanced-stage ovarian cancer, large-volume ascites and a longer interval between chemotherapy and cytoreductive surgery were associated with more port-site recurrences. In addition, full-layer closure of the abdominal wall reduced port-site recurrences from 58% to 2%, emphasizing the importance of trocar-site closure in cases of malignancy. There was no survival disadvantage in women with portsite recurrences.

What causes port-site recurrences?

Possible factors include:

• trauma to the site,
• frequent removal of instruments through the port,
• removing the specimen through the port, and
• continued leakage of ascites.¹³

Avoiding cyst spillage and routinely using laparoscopic bags for cyst removal may decrease the incidence of these recurrences (FIGURE 1). Partial cyst excision and morcellation of a solid mass are always contraindicated.

Irrigation of port sites may decrease tumor cell implantation and should be considered at the end of the procedure.¹³ To further reduce risk, experts recommend closing all layers at the time of laparoscopy and resecting laparoscopic ports in their full thickness at the time of the staging laparotomy.¹⁴

FIGURE 1 Cyst removal using an endoscopic bag

Avoid spillage and routinely use laparoscopic bags for cyst removal to decrease the incidence of port-site recurrences.

Hand-Assisted Laparoscopy

This hybrid procedure combines the advantages of minimally invasive surgery with the tactile sensation of laparotomy. It has gained favor among urologists and general surgeons. (The first nephrectomy using this method was performed in 1996.¹⁷)

Technological advances now enable the surgeon to insert and remove the nondominant hand into the peritoneal cavity without losing pneumoperitoneum and to insert instruments through the same port if needed (FIGURE 2).

Advantages over traditional laparoscopy include the ability to palpate tissue, assist with tissue retraction, perform blunt dissection, and rapidly control hemostasis. This approach has been described in management and staging of early-stage ovarian cancer and in debulking advanced disease.¹⁸

 

FIGURE 2 Hand-assisted laparoscopy

The nondominant hand and surgical instruments can be inserted and removed through the special port without affecting pneumoperitoneum.

Surgical Staging

Maria’ case

resection and analysis of ovary

Maria underwent laparoscopy via the open technique. The surgeon found a cystic right ovarian mass, a fibroid uterus, and small diaphragmatic nodules, which were biopsied and found to be benign.

Pelvic washings were obtained, and after the right infundibular pelvic ligament and right utero-ovarian ligament were clamped and cut, the intact ovary was placed in a laparoscopic bag. The bag was pulled through the 12-mm suprapubic trocar, the cyst wall was perforated, and the cyst was drained within the laparoscopic bag, producing brown fluid. The bag was removed from the peritoneal cavity through this port, and the cyst was sent to pathology.

There was no contamination to the peritoneal cavity or abdominal wall, and the bag remained intact. Surgical gloves were then changed, and instruments used to drain the cyst were removed from the operating field.

When frozen-section analysis revealed a borderline serous ovarian tumor, Maria underwent BSO, infracolic omentectomy, laparoscopic pelvic and paraaortic lymphadenectomy, and laparoscopically assisted vaginal hysterectomy. There were no intraoperative complications, the total time in the operating room was 330 minutes, and there was blood loss of approximately 150 mL.

When an ovarian malignancy is discovered, immediate staging is indicated, and should include:

• peritoneal biopsies,
• pelvic and para-aortic lymph node sampling,
• infracolic omentectomy, and
• bilateral salpingo-oophorectomy (BSO) and hysterectomy.¹

With presumed stage I disease, there is a 20% to 30% likelihood of upstaging after comprehensive surgical staging, with disease often discovered in the lymph nodes.^19,20

Since changes in staging affect prognosis and treatment, complete staging should include the retroperitoneal nodes.

When the patient wants to preserve fertility

In selected younger women who have not yet completed childbearing, conservative treatment with retention of the uterus and contralateral ovary is an option—though we lack outcomes data on patients treated this way.

This option should be restricted to women with proven stage I disease after comprehensive staging.¹

Can staging be done laparoscopically?

Complete staging—consisting of a detailed peritoneal assessment (with BSO and vaginal hysterectomy), omentectomy, and pelvic and para-aortic node dissection—can safely be done laparoscopically.^19-21 Studies show low morbidity, with accurate findings and adequate node counts.^21,22

A comparison of laparoscopic and conventional (laparotomy) staging in women with apparent stage I adnexal cancers found no differences in omental specimen size or the number of lymph nodes removed, and none of the patients required conversion to laparotomy.²²

When definitive staging is delayed

Several studies have found poorer outcomes with delayed staging. However, the tumor ruptured in some of these studies, with considerable delay from the initial laparoscopy until definitive staging and treatment.

To increase the likelihood of an accurate stage, gather as much information as possible on the extent of disease: Describe the intraoperative findings and inspect the abdomen and pelvis thoroughly at initial surgery if a skilled oncologic surgeon is not immediately available. Then make every effort to schedule a complete staging procedure as soon as possible, as some consider this an “oncologic emergency.”⁹

Whether and when to stage LMP tumors

Preoperative prediction and intraoperative diagnosis of low malignant potential (LMP) tumors is challenging. If such a tumor is confirmed by frozen section, the usual treatment is unilateral salpingo-oophorectomy. When the patient is postmenopausal or has completed childbearing, BSO, hysterectomy, and staging should be considered.¹

Surgical staging should be performed at the initial surgery, if at all possible. However, if final pathology confirms an LMP tumor and disease appears to be confined to the adnexa, repeat surgery for staging is controversial because of the limited data on its benefit, particularly in regard to mucinous borderline tumors.

Restaging may be more useful in selected cases of serous LMP tumors with histologic micropapillary features, since these tumors may be associated with a higher incidence of invasive implants (eg, in the omentum or peritoneum) that may require chemotherapy.

If a malignant cyst ruptures, does it affect staging?

The effect of intraoperative tumor spillage in stage I disease is debatable, although ascites and preoperative rupture are associated with a poorer prognosis.²³

Even though a number of investigators (TABLE) have found intraoperative spillage to have no adverse impact on survival, make every effort to maintain capsular integrity to minimize any possibility of peritoneal tumor dissemination.

In some cases, intraoperative cyst rupture warrants upstaging from International Federation of Gynecology and Obstetrics (FIGO) stage IA to 1C, necessitating adjuvant chemotherapy when it otherwise would not have been required.¹

 

Cyst rupture is no more likely with laparoscopy than with laparotomy,² and is unrelated to the surgical route. It is more closely associated with the frequency of cystectomy.²⁴

If rupture does occur, thoroughly irrigate the peritoneal cavity.

TABLE

When a cyst ruptures during surgery, what is the prognosis? The data are mixed on the significance of this event in stage I ovarian cancer

AUTHOR	NUMBER OF CASES	IMPACT
Sevelda 1990 (Austria)	204	No prognostic importance
Sainz 1994 (US)	79	May worsen prognosis
Sjovall 1994 (Sweden)	394	No negative influence
Ahmed 1996 (UK)	194	Not prognostically significant
Vergote 2001 (Belgium)	1,545	Rupture should be avoided (hazard ratio = 1.64)

How chemotherapy comes into play

If final pathology shows stage IC or high-grade histology, chemotherapy generally is offered to women managed in the United States. In selected cases, chemotherapy is given immediately after the initial surgery if completing a full staging procedure would considerably delay chemotherapy.

Leblanc et al²¹ found that, when staging was performed after completion of chemotherapy in women with stage IC or high-grade histology, 3 of 11 patients (27%) had positive nodes. Because positive nodes can be less chemosensitive, Leblanc and colleagues advocate either of 2 options: immediate restaging, including retroperitoneal nodes, or staging after chemotherapy, including retroperitoneal nodes.

Advanced Ovarian Cancer

Optimal surgical cytoreduction by laparotomy, followed by platinum-based chemotherapy, maximizes survival in women with advanced ovarian cancer. Unfortunately, in many patients, optimal debulking is not feasible, and laparotomy without optimal cytoreduction offers no survival advantage.²⁵ At the same time, preoperative imaging has limited ability to determine the feasibility of cytoreduction. For example, computed tomography is highly sensitive when it comes to detecting ascites and mesenteric and omental disease (FIGURE 3), but is not as successful in detecting gallbladder fossa disease and diffuse peritoneal nodules smaller than 2 cm.

As a result, laparoscopy is increasingly used to determine whether optimal resection is feasible. If it is, immediate laparotomy is appropriate. Otherwise, a tissue specimen is obtained for histological confirmation, allowing accurate diagnosis prior to chemotherapy.

FIGURE 3 Omental cake signifies metastasis

Omental cake in a stage IIIC ovarian cancer patient. Disease appears to be resectable.

Potential drawbacks of laparoscopy

In selected women with advanced cancer, laparoscopy may be a good way to determine which patients would not benefit from laparotomy, thus sparing them the morbidity of an additional operation. But laparoscopy can have limitations:

• Ascites can reduce visibility.
• Omental and bowel adhesion to the anterior abdominal wall may increase the likelihood of bowel injury.
• Trocar site implantation may increase in the presence of adenocarcinoma, ascites, and carcinomatosis.¹³

If trocar sites are carefully closed and chemotherapy is initiated promptly, these risks can be substantially reduced.¹⁴

 

Second-Look Laparoscopy

Second-look surgery in women with a complete clinical response (normal exam, imaging, and CA125) after primary chemotherapy is controversial. This surgery aims to identify women with pathologically negative or microscopic disease who may benefit from consolidation therapy, or with larger-volume disease who can undergo secondary cytoreduction.²⁷ Laparoscopy meets these goals safely with comparable accuracy and less morbidity than laparotomy.^12,27

Maria’ case

lmp tumor and negative nodes

Maria did well postoperatively and went home on day 4. Her final pathology report: a right papillary serous adenocarcinoma of LMP (borderline) with small (<1 mm) foci of microinvasion. She had 6 negative paraaortic nodes, 19 negative pelvic nodes, negative pelvic washings and omentum, a normal left ovary, and a 6-cm cellular leiomyoma in an otherwise normal uterus.

She required no adjuvant treatment and is now 22 months postoperative without evidence of disease.

The authors report no financial relationships relevant to this article.