Gynecology

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.

Pain is the most debilitating symptom of endometriosis.^1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.^3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.⁵ The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.^6-8

Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.^5,9,10 These discoveries have important treatment implications.

In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.

Q What mechanisms underlie the chronic pain that many women with endometriosis feel?

Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.^11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”

Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”

“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”

Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...

Q What other chronic pain conditions might women with endometriosis experience?

Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”

“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”

“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”

Continue to: Q How have new understandings about the pain mechanisms...

According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.

“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).¹⁴ This also has been shown by Dr. Berkley in rodents given endometriosis.

“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”

Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.¹⁶ “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”

Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?

Q What are some newer treatment approaches to chronic pain with endometriosis?

“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”

Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”

A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”

“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”

Q What key pearls would you like to share with readers?

“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”

“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.

Pain is the most debilitating symptom of endometriosis.^1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.^3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.⁵ The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.^6-8

Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.^5,9,10 These discoveries have important treatment implications.

In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.

Q What mechanisms underlie the chronic pain that many women with endometriosis feel?

Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.^11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”

Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”

“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”

Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...

Q What other chronic pain conditions might women with endometriosis experience?

Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”

“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”

“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”

Continue to: Q How have new understandings about the pain mechanisms...

According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.

“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).¹⁴ This also has been shown by Dr. Berkley in rodents given endometriosis.

“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”

Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.¹⁶ “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”

Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?

Q What are some newer treatment approaches to chronic pain with endometriosis?

“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”

Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”

A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”

“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”

Q What key pearls would you like to share with readers?

“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”

“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Although it has been more than 100 years since endometriosis was first described in the literature, deciphering the mechanisms that cause pain in women with this enigmatic disease is an ongoing pursuit.

Pain is the most debilitating symptom of endometriosis.^1,2 In many cases, it has a profoundly negative impact on a patient’s quality of life, and contributes significantly to disease burden, as well as to personal and societal costs from lost productivity.^3,4 Women with endometriosis often experience chronic pelvic pain, deep dyspareunia, dysmenorrhea, and subfertility.⁵ The majority of women with the disease also have one or more comorbidities, including adenomyosis, adhesive disease, and other pelvic pain conditions such as interstitial cystitis, irritable bowel disease, inflammatory bowel disease, and pelvic floor myalgia.^6-8

Recent studies have yielded new insights into the development of endometriosis-associated pelvic pain. The role of peritoneal inflammation, de novo innervation of endometriosis implants, and changes in the central nervous system are becoming increasingly clear.^5,9,10 These discoveries have important treatment implications.

In this article, Andrea J. Rapkin, MD, Professor of Obstetrics and Gynecology at the University of California, Los Angeles, and Founder and Director of the UCLA Pelvic Pain Center, offers her expert opinion on the findings of key studies and their clinical implications, including the importance of a multidisciplinary treatment approach that focuses on the whole patient.

Q What mechanisms underlie the chronic pain that many women with endometriosis feel?

Although pain is the primary symptom experienced by women with endometriosis, the disease burden and symptom severity do not often correlate.^11,12 “This was the first conundrum presented to clinicians,” noted Dr. Rapkin. “In fact, we do not know the true prevalence of endometriosis because women with endometriosis only come to diagnosis either based on pain or infertility. When infertility is the problem, very often we are surprised by how much disease is present in an individual with either no pain or minimal pain. Conversely, in other individuals with very severe pain, upon laparoscopic surgery, have minimal or mild endometriosis.”

Efforts to solve this clinical puzzle began decades ago. “Dr. Michael Vernon discovered that the small, red, endometriosis implants that looked like petechial hemorrhages produced more prostaglandin E2 (PGE2) in vitro than the older black-brown lesions. PGE2 is a pain-producing (algesic) chemical produced after cytokines stimulation,” said Dr. Rapkin. “This was the first evidence that, yes, there is a reason for pain in many individuals with lower-stage disease.”

“Prostaglandins are known to be a major cause of dysmenorrhea. Prostaglandins induce uterine cramping, sensitize nerve endings, and promote other inflammatory factors responsible for attracting monocytes that become macrophages, further contributing to inflammation,” Dr. Rapkin continued. “PGE2 also stimulates the enzyme aromatase, which allows androgens to be converted to estrogen, which promotes growth of endometriotic lesions. This is a self-feeding aspect of endometriosis.”

Continue to: These discoveries were followed by the realization that deeply infiltrating endometriosis...

Q What other chronic pain conditions might women with endometriosis experience?

Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”

“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”

“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”

Continue to: Q How have new understandings about the pain mechanisms...

According to Dr. Rapkin, the increased understanding of the mechanisms involved in endometriosis-associated pain gained from these key studies led to a paradigm shift, with endometriosis being viewed not just as a condition with mechanical hypersensitivity due to altered anatomy and inflammation but also as a neurologic condition, or a nerve pain condition with peripheral and central sensitization. “This means there is upregulation or hyperactivity both in the periphery (in the pelvis) and centrally (in the spinal cord and brain),” said Dr. Rapkin.

“In the periphery, the endometriotic lesions develop an afferent sensory innervation and communicate with the brain. Stimulation of these nerves by the inflammatory milieu contributes to pain.” Dr. Rapkin noted research by Maria Adele Giamberardino, which demonstrated that women with endometriosis and pain have a lower threshold for feeling pain in the tissues overlying the pelvis (the abdominal wall and back).¹⁴ This also has been shown by Dr. Berkley in rodents given endometriosis.

“The muscles develop trigger points and tender hyperalgesic points as part of the sensitization process. In addition, distant sensitization develops—women with pelvic pain and endometriosis have a lower threshold for sensing experimental pain in areas outside the pelvis, for example the back, leg, or shoulder. These discoveries clearly reflect up regulation for pain processing in the central nervous system.”

Dr. Rapkin also pointed to research published in 2016 by Sawson As-Sanie, MD, MPH, that showed an association between endometriosis-associated pelvic pain and altered brain chemistry and function.¹⁶ “Dr. As-Sanie demonstrated a decrease in gray matter volume in key neural pain processing areas in the brain in women with pain with endometriosis. This was not found in women with endometriosis who did not have pain,” she said. “Altered connectivity in brain areas related to perception and inhibition of pain is important in maintaining pain. Dr. As-Sanie’s studies also found that these changes are correlated with anxiety, depression, and pain intensity in patients with endometriosis and chronic pain.”

Continue to: Q What are some newer treatment approaches to chronic pain with endometriosis?

Q What are some newer treatment approaches to chronic pain with endometriosis?

“Multidisciplinary approaches to endometriosis-related pain are important,” said Dr. Rapkin. “Although it is important to excise or cauterize endometriosis lesions, or debulk as much as can safely be removed during laparoscopic surgery, it is now standard of care that medical therapy, not surgery, is the first approach to treatment. Endometriosis is a chronic condition. Inflammatory factors will continue to proliferate in patients who menstruate and produce high levels of estrogen with ovulation. The goal of medical therapy is to decrease the levels of estrogen that contribute to maintenance and proliferation of the implants. We want to suppress estrogen in a way that is compatible with long-term quality of life for our patients. Wiping out estrogen and placing patients into a chemical or surgical menopause for most of their reproductive years is not desirable.”

Approaches to hormonally modulate endometriosis include combined hormonal contraceptives and progestin-only medications, such as the levonogestrol-containing IUD, progestin-containing contraceptive implants, injections, or tablets. Second-line medical therapy consists of gonadotropin-releasing hormone agonists and antagonists that can be used for 6 months to 2 years and allows for further lowering of estrogen levels. These may not provide sufficient pain relief for some patients. “There is some evidence from Dr. Giamberadino’s studies that after women with dysmenorrhea were treated with oral contraceptives, the abdominal wall hyperalgesia decreased,” said Dr. Rapkin. “The question is, why don’t we see this in all patients? We come to the realization that endometriosis has to be treated as a neurologically mediated disorder. We have to treat the peripheral and central sensitization in a multidisciplinary way.”

A holistic approach to endometriosis is a new and exciting area for the field, said Dr. Rapkin. “We have to treat ‘bottom-up’, and ‘top-down.’ Bottom-up means we are addressing the peripheral factors that contribute to pain: endometriotic lesions, other pelvic organ pain, myofascial pain, trigger points, the tender points, and the muscle dysfunction in the abdominal wall, the back, and the pelvic floor. Pelvic floor physical therapists help women with pain and endometriosis. Often, women with endometriosis have myofascial pain and pain related to the other comorbid pain conditions they may have developed. Peripheral nerve blocks and medications used for neuropathic pain that alter nerve firing can be helpful in many situations. Pain can be augmented by cognitions and beliefs about pain, and by anxiety and depression. So the top-down approach addresses the cognitions, depression, and anxiety. We do not consider endometriosis a psychosomatic condition, but we know that if you do not address the central upregulation, including anxiety and depression, we may not get anywhere.”

“Interestingly, neurotransmitters and brain regions governing mood contribute to nerve pain. Medications such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, anticonvulsants, and calcium channel blocking agents may prove fruitful. Cognitive behavioral therapy is another approach—to stimulate the prefrontal cortex, the area that is involved in pain inhibition, and other areas of the brain that may produce endogenous opioids to help with inhibiting pain. Bringing in complementary approaches is very important—for example, mindfulness-based meditation or yoga. There is growing evidence for acupuncture as well. Physical therapists, pain psychologists, anesthesiologists, or gynecologists who are facile with nerve blocks, to help tone down hyperalgesic tissues, in addition to medical and surgical therapy, have the possibility of really improving the lives of women with endometriosis.”

Q What key pearls would you like to share with readers?

“It is important to evaluate the entire individual,” she said. “Do not just viscerally focus on the uterus, the ovaries, fallopian tubes, and the peritoneum; investigate the adjacent organs and somatic tissues. Think about the abdominal wall, think about the pelvic floor. Learn how to evaluate these structures. There are simple evaluation techniques that gynecologists can learn and should include with every patient with pelvic pain, whether or not they are suspected of having endometriosis. You also want to get a complete history to determine if there are other co-occurring pain conditions. If there are, it is already a sign that there may be central sensitization.”

“Very often, it is necessary to bring in a pain psychologist—not because the disease is psychosomatic but because therapy can help the patient to learn how to use their brain to erase pain memory, and of course to address the concomitant anxiety, depression, and social isolation that happens with pain.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

LAS VEGAS – Patients like cold packs for pain control after laparoscopic hysterectomy, according to a small trial from Cleveland Clinic Florida (Weston).

M. Alexander Otto/MDedge News

Cold packs have been shown to reduce pain in other types of surgery, so investigators at the clinic wanted to try them out for the procedure, said study lead Pamela Frazzini Padilla, MD, an ob.gyn. at the clinic.

Twenty-eight women were randomized to get packs right after surgery, and told to use them – before turning to oxycodone tabs – every 6 hours for 72 hours – and then as needed. Twenty-eight other women were randomized to the control group. Surgery was for benign indications, most often uterine bleeding secondary to fibroids. Besides the cold packs, there were no differences between the groups in analgesia protocols.

The differences in pain control, assessed on a 10-point scale over the phone, weren’t statistically significant, but they di move in the right direction. At 24 hours, women who were cold pack users reported a median pain score of 4, versus 4.5 among controls. At 72 hours, they reported a median score of 2, versus 2.5 in the control group.

At 2 weeks postoperatively, women who were cold pack users had used a mean of 4 oxycodone pills, versus 7 among the controls, which translated into a mean of 13 IV morphine equivalents versus 24 in favor of cold packs (P = .143).

While not significantly different, overall numbers of opioid tabs consumed and morphine equivalents “demonstrated lower use in the study group,” Dr. Frazzini Padilla noted at the meeting sponsored by AAGL.

Also, 89% of women said that cold packs helped reduce their pain, and 92% said they’d use them again after an operation. “In a day when everything is driven by patient satisfaction, patients’ perception of their recovery” is important. Because cold packs are cheap, harmless, and seemed to help with patient perceptions, “we do recommend that people use” them. “It’s just another added measure that we give” at Cleveland Clinic Florida, she said.

The study team also found that 86% of the women in the trial used 10 or fewer oxycodone tabs after surgery. Across the country, women are prescribed about 25 tabs after a laparoscopic hysterectomy; the study suggests it’s overkill, as an audience member noted, especially given the current climate.

The two arms of the study were well balanced. The mean age was 46 years, and mean body mass index 30.4 kg/m².

There was no outside funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Frazzini Padilla P et al. 2018 AAGL Global Congress, Abstract 21.

LAS VEGAS – Patients like cold packs for pain control after laparoscopic hysterectomy, according to a small trial from Cleveland Clinic Florida (Weston).

M. Alexander Otto/MDedge News

Cold packs have been shown to reduce pain in other types of surgery, so investigators at the clinic wanted to try them out for the procedure, said study lead Pamela Frazzini Padilla, MD, an ob.gyn. at the clinic.

Twenty-eight women were randomized to get packs right after surgery, and told to use them – before turning to oxycodone tabs – every 6 hours for 72 hours – and then as needed. Twenty-eight other women were randomized to the control group. Surgery was for benign indications, most often uterine bleeding secondary to fibroids. Besides the cold packs, there were no differences between the groups in analgesia protocols.

The differences in pain control, assessed on a 10-point scale over the phone, weren’t statistically significant, but they di move in the right direction. At 24 hours, women who were cold pack users reported a median pain score of 4, versus 4.5 among controls. At 72 hours, they reported a median score of 2, versus 2.5 in the control group.

At 2 weeks postoperatively, women who were cold pack users had used a mean of 4 oxycodone pills, versus 7 among the controls, which translated into a mean of 13 IV morphine equivalents versus 24 in favor of cold packs (P = .143).

While not significantly different, overall numbers of opioid tabs consumed and morphine equivalents “demonstrated lower use in the study group,” Dr. Frazzini Padilla noted at the meeting sponsored by AAGL.

Also, 89% of women said that cold packs helped reduce their pain, and 92% said they’d use them again after an operation. “In a day when everything is driven by patient satisfaction, patients’ perception of their recovery” is important. Because cold packs are cheap, harmless, and seemed to help with patient perceptions, “we do recommend that people use” them. “It’s just another added measure that we give” at Cleveland Clinic Florida, she said.

The study team also found that 86% of the women in the trial used 10 or fewer oxycodone tabs after surgery. Across the country, women are prescribed about 25 tabs after a laparoscopic hysterectomy; the study suggests it’s overkill, as an audience member noted, especially given the current climate.

The two arms of the study were well balanced. The mean age was 46 years, and mean body mass index 30.4 kg/m².

There was no outside funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Frazzini Padilla P et al. 2018 AAGL Global Congress, Abstract 21.

LAS VEGAS – Patients like cold packs for pain control after laparoscopic hysterectomy, according to a small trial from Cleveland Clinic Florida (Weston).

M. Alexander Otto/MDedge News

Cold packs have been shown to reduce pain in other types of surgery, so investigators at the clinic wanted to try them out for the procedure, said study lead Pamela Frazzini Padilla, MD, an ob.gyn. at the clinic.

Twenty-eight women were randomized to get packs right after surgery, and told to use them – before turning to oxycodone tabs – every 6 hours for 72 hours – and then as needed. Twenty-eight other women were randomized to the control group. Surgery was for benign indications, most often uterine bleeding secondary to fibroids. Besides the cold packs, there were no differences between the groups in analgesia protocols.

The differences in pain control, assessed on a 10-point scale over the phone, weren’t statistically significant, but they di move in the right direction. At 24 hours, women who were cold pack users reported a median pain score of 4, versus 4.5 among controls. At 72 hours, they reported a median score of 2, versus 2.5 in the control group.

At 2 weeks postoperatively, women who were cold pack users had used a mean of 4 oxycodone pills, versus 7 among the controls, which translated into a mean of 13 IV morphine equivalents versus 24 in favor of cold packs (P = .143).

While not significantly different, overall numbers of opioid tabs consumed and morphine equivalents “demonstrated lower use in the study group,” Dr. Frazzini Padilla noted at the meeting sponsored by AAGL.

Also, 89% of women said that cold packs helped reduce their pain, and 92% said they’d use them again after an operation. “In a day when everything is driven by patient satisfaction, patients’ perception of their recovery” is important. Because cold packs are cheap, harmless, and seemed to help with patient perceptions, “we do recommend that people use” them. “It’s just another added measure that we give” at Cleveland Clinic Florida, she said.

The study team also found that 86% of the women in the trial used 10 or fewer oxycodone tabs after surgery. Across the country, women are prescribed about 25 tabs after a laparoscopic hysterectomy; the study suggests it’s overkill, as an audience member noted, especially given the current climate.

The two arms of the study were well balanced. The mean age was 46 years, and mean body mass index 30.4 kg/m².

There was no outside funding, and the investigators didn’t have any disclosures.

aotto@mdedge.com

SOURCE: Frazzini Padilla P et al. 2018 AAGL Global Congress, Abstract 21.

LAS VEGAS – It’s fine to take a peek inside the bladder with the laparoscope after robotic hysterectomy; there’s no need for a separate cystoscopy setup to check for injuries, according to a review from St. Joseph’s University Medical Center, in Paterson, N.J.

Master Video/Shutterstock

Postoperative urinary tract infections (UTIs) are the big worry with using the same scope, but they really weren’t a problem at St. Joe’s; in a study of 45 women, there was just one UTI, confirmed by culture, at the 2-week postoperative visit, yielding a rate (2.2%) that is actually better the 5%-10% reported for stand-alone cystoscopy, said lead investigator and ob.gyn. resident Nikki Amirlatifi, MD.

“This is a safe alternative to traditional cystoscopy. We had no problems with visualization, and it doesn’t increase the rate of UTIs. Of course, it’s not only cost saving but time saving, as well,” she said.

The cases all were routine, however. For tougher ones, “where we need a more in-depth look at the bladder, we would [still] do cystoscopy,” she said at the meeting sponsored by AAGL.

There’s some debate about routine cystoscopy during laparoscopic hysterectomy, but Dr. Amirlatifi noted that it’s been reported to detect up to 89% of ureter injuries and up to 95% of bladder injuries. Using the same scope for both procedures makes it easier.

After the uterus was taken out, the bladder was backfilled with 180 mL of sterile water, then the Foley catheter was pulled. The previously used 5 mm laparoscope, which had been used for abdominal entry at 0 degrees, was introduced into the bladder. Efflux from both ureteral orifices was visualized, then the catheter reinserted until the end of surgery.

The women were an average of 44 years old, with an average body mass index of 32 kg/m². Abnormal uterine bleeding, pelvic pain, and fibroids were the main indications for surgery. No ureteral or bladder injuries were detected.

Everyone was questioned about UTI symptoms and gave a clean-catch urine sample at the first postoperative visit. Cultures were performed on the seven women who reported symptoms or had white cells in their sample, and they were treated empirically with antibiotics. Only one culture grew out despite a high prevalence of UTI risk factors, including diabetes (13%), obesity (42%), and smoking (11%).

All the women had preoperative antibiotics and phenazopyridine. Most went home on the day of surgery.

There was no outside funding for the work, and the investigators didn’t have any relevant financial disclosures.

aotto@mdedge.com

SOURCE: J Minim. Invasive Gynecol. 2018 Nov-Dec;25[7]:S46-47.

LAS VEGAS – It’s fine to take a peek inside the bladder with the laparoscope after robotic hysterectomy; there’s no need for a separate cystoscopy setup to check for injuries, according to a review from St. Joseph’s University Medical Center, in Paterson, N.J.

Master Video/Shutterstock

Postoperative urinary tract infections (UTIs) are the big worry with using the same scope, but they really weren’t a problem at St. Joe’s; in a study of 45 women, there was just one UTI, confirmed by culture, at the 2-week postoperative visit, yielding a rate (2.2%) that is actually better the 5%-10% reported for stand-alone cystoscopy, said lead investigator and ob.gyn. resident Nikki Amirlatifi, MD.

“This is a safe alternative to traditional cystoscopy. We had no problems with visualization, and it doesn’t increase the rate of UTIs. Of course, it’s not only cost saving but time saving, as well,” she said.

The cases all were routine, however. For tougher ones, “where we need a more in-depth look at the bladder, we would [still] do cystoscopy,” she said at the meeting sponsored by AAGL.

There’s some debate about routine cystoscopy during laparoscopic hysterectomy, but Dr. Amirlatifi noted that it’s been reported to detect up to 89% of ureter injuries and up to 95% of bladder injuries. Using the same scope for both procedures makes it easier.

After the uterus was taken out, the bladder was backfilled with 180 mL of sterile water, then the Foley catheter was pulled. The previously used 5 mm laparoscope, which had been used for abdominal entry at 0 degrees, was introduced into the bladder. Efflux from both ureteral orifices was visualized, then the catheter reinserted until the end of surgery.

The women were an average of 44 years old, with an average body mass index of 32 kg/m². Abnormal uterine bleeding, pelvic pain, and fibroids were the main indications for surgery. No ureteral or bladder injuries were detected.

Everyone was questioned about UTI symptoms and gave a clean-catch urine sample at the first postoperative visit. Cultures were performed on the seven women who reported symptoms or had white cells in their sample, and they were treated empirically with antibiotics. Only one culture grew out despite a high prevalence of UTI risk factors, including diabetes (13%), obesity (42%), and smoking (11%).

All the women had preoperative antibiotics and phenazopyridine. Most went home on the day of surgery.

There was no outside funding for the work, and the investigators didn’t have any relevant financial disclosures.

aotto@mdedge.com

SOURCE: J Minim. Invasive Gynecol. 2018 Nov-Dec;25[7]:S46-47.

LAS VEGAS – It’s fine to take a peek inside the bladder with the laparoscope after robotic hysterectomy; there’s no need for a separate cystoscopy setup to check for injuries, according to a review from St. Joseph’s University Medical Center, in Paterson, N.J.

Master Video/Shutterstock

Postoperative urinary tract infections (UTIs) are the big worry with using the same scope, but they really weren’t a problem at St. Joe’s; in a study of 45 women, there was just one UTI, confirmed by culture, at the 2-week postoperative visit, yielding a rate (2.2%) that is actually better the 5%-10% reported for stand-alone cystoscopy, said lead investigator and ob.gyn. resident Nikki Amirlatifi, MD.

“This is a safe alternative to traditional cystoscopy. We had no problems with visualization, and it doesn’t increase the rate of UTIs. Of course, it’s not only cost saving but time saving, as well,” she said.

The cases all were routine, however. For tougher ones, “where we need a more in-depth look at the bladder, we would [still] do cystoscopy,” she said at the meeting sponsored by AAGL.

There’s some debate about routine cystoscopy during laparoscopic hysterectomy, but Dr. Amirlatifi noted that it’s been reported to detect up to 89% of ureter injuries and up to 95% of bladder injuries. Using the same scope for both procedures makes it easier.

After the uterus was taken out, the bladder was backfilled with 180 mL of sterile water, then the Foley catheter was pulled. The previously used 5 mm laparoscope, which had been used for abdominal entry at 0 degrees, was introduced into the bladder. Efflux from both ureteral orifices was visualized, then the catheter reinserted until the end of surgery.

The women were an average of 44 years old, with an average body mass index of 32 kg/m². Abnormal uterine bleeding, pelvic pain, and fibroids were the main indications for surgery. No ureteral or bladder injuries were detected.

Everyone was questioned about UTI symptoms and gave a clean-catch urine sample at the first postoperative visit. Cultures were performed on the seven women who reported symptoms or had white cells in their sample, and they were treated empirically with antibiotics. Only one culture grew out despite a high prevalence of UTI risk factors, including diabetes (13%), obesity (42%), and smoking (11%).

All the women had preoperative antibiotics and phenazopyridine. Most went home on the day of surgery.

There was no outside funding for the work, and the investigators didn’t have any relevant financial disclosures.

aotto@mdedge.com

SOURCE: J Minim. Invasive Gynecol. 2018 Nov-Dec;25[7]:S46-47.

Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.

©Catherine Yeulet/thinkstockphotos.com

The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.

“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”

In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.

The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.

“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.

Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.

The authors reported no relevant conflicts of interest.

SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.

Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.

©Catherine Yeulet/thinkstockphotos.com

The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.

“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”

In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.

The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.

“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.

Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.

The authors reported no relevant conflicts of interest.

SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.

Over one-third of adolescents presenting with heavy menstrual bleeding were diagnosed with a bleeding disorder after screening, according to results of a retrospective study.

©Catherine Yeulet/thinkstockphotos.com

The high incidence of bleeding disorders detected argues for routine screening of adolescents with heavy menstrual bleeding (HMB), Brooke O’Brien, MD, of the University of Queensland, Brisbane, Australia, and her colleagues wrote in the Journal of Pediatric & Adolescent Gynecology.

“These findings support comprehensive and systematic hemostatic evaluation in adolescents with HMB,” Dr. O’Brien and her colleagues wrote. “A higher level of awareness of bleeding disorders as a cause for HMB in adolescence, especially [von Willebrand disease] and platelet function disorders, is needed and close multidisciplinary collaboration between the pediatric and adolescent gynecologist and hematologist in a specialized tertiary center should be established in the management of these patients.”

In their study, Dr. O’Brien and her colleagues retrospectively evaluated 124 adolescents with HMB at a pediatric and adolescent gynecology tertiary care center between July 2007 and July 2017. Of these, 77 patients (62.1%) underwent screening for blood disorders.

The researchers found 27 adolescents overall were diagnosed with a blood disorder, which consisted of 35.0% of patients screened and 21.7% of all patients studied. Specifically, 14 of 27 patients (51.6%) screened were diagnosed with von Willebrand disease, 9 of 27 patients (33.3%) screened were found to have inherited platelet function disorders, 3 of 27 patients (11.1%) had inherited or acquired thrombocytopenia, and 1 of 27 patients (3.7%) had factor IX deficiency. The researchers also screened for iron deficiency and/or anemia and found 53 of 107 patients (49.5%) who were screened received a diagnosis, and 19 of 27 patients (70.3%) who were diagnosed with a bleeding disorder also had iron deficiency and/or anemia.

“In adolescents who are already known to have a bleeding disorder, consultation with a pediatric gynecologist and/or hematologist prior to menarche may be helpful to outline abnormal patterns of menstrual bleeding and to discuss options of treatment in the event of heavy menstrual bleeding,” Dr. O’Brien and her colleagues wrote.

Potential limitations in the study include the refractory nature of referrals at a tertiary care center potentially overestimating the prevalence of HMB in this population as well as the study’s retrospective design when investigating and measuring heavy menstrual bleeding, but researchers noted patients were reviewed and classified by a specialist pediatric hematologist.

The authors reported no relevant conflicts of interest.

SOURCE: O’Brien B et al. J Pediatr Adolesc Gynecol. 2018 Nov 22. doi: 10.1016/j.jpag.2018.11.005.

LAS VEGAS – When stage IV endometriosis with obliterated posterior cul-de-sac is discovered during laparoscopic hysterectomy, or suspected beforehand, women should be referred to a minimally invasive gynecologic surgery specialist because the procedure will be much more difficult, investigators said at the meeting sponsored by AAGL.

M. Alexander Otto/MDedge News

They reviewed 333 laparoscopic hysterectomies where endometriosis was discovered in the operating room. The disease is known to increase the complexity of hysterectomy; the investigators wanted to quantify the risk by endometriosis severity. Among their subjects, 237 women (71%) had stage I, II, or III endometriosis; 96 (29%) had stage IV disease, including 55 women (57%) with obliterated posterior cul-de-sacs.

Surgery was longer among stage IV cases (137 vs. 116 minutes), and there was greater blood loss; 66% of stage IV women required laparoscopic-modified radical hysterectomy versus about a quarter of women with stage I-III endometriosis.

Laparoscopic hysterectomy was even more complex when women with stage IV endometriosis had obliterated cul-de-sacs. A total of 93% required modified radical hysterectomies versus 29% of stage IV women with intact cul-de-sacs. Additional procedures were far more likely in this population, including salpingectomy, ureterolysis, enterolysis, cystoscopy, ureteral stenting, proctoscopy, bowel oversew, and anterior resection anastomosis. The differences all were statistically significant.

Among stage IV cases, mean operating time was longer in obliterated cul-de-sac cases (159 vs. 108 minutes), with higher blood loss, 100 mL versus 50 mL.

“Patients with obliterated cul-de-sacs identified intraoperatively should be referred to minimally invasive gynecologic surgeons because of the ... extra training required to safely perform [laparoscopic hysterectomy] with limited morbidity,” said lead investigator Alexandra Melnyk, MD, a University of Pittsburgh ob.gyn resident.

There was no industry funding and the investigators reported no disclosures.

aotto@mdedge.com

SOURCE: Melnyk A et al. 2018 AAGL Global Congress, Abstract 81.

LAS VEGAS – When stage IV endometriosis with obliterated posterior cul-de-sac is discovered during laparoscopic hysterectomy, or suspected beforehand, women should be referred to a minimally invasive gynecologic surgery specialist because the procedure will be much more difficult, investigators said at the meeting sponsored by AAGL.

M. Alexander Otto/MDedge News

They reviewed 333 laparoscopic hysterectomies where endometriosis was discovered in the operating room. The disease is known to increase the complexity of hysterectomy; the investigators wanted to quantify the risk by endometriosis severity. Among their subjects, 237 women (71%) had stage I, II, or III endometriosis; 96 (29%) had stage IV disease, including 55 women (57%) with obliterated posterior cul-de-sacs.

Surgery was longer among stage IV cases (137 vs. 116 minutes), and there was greater blood loss; 66% of stage IV women required laparoscopic-modified radical hysterectomy versus about a quarter of women with stage I-III endometriosis.

Laparoscopic hysterectomy was even more complex when women with stage IV endometriosis had obliterated cul-de-sacs. A total of 93% required modified radical hysterectomies versus 29% of stage IV women with intact cul-de-sacs. Additional procedures were far more likely in this population, including salpingectomy, ureterolysis, enterolysis, cystoscopy, ureteral stenting, proctoscopy, bowel oversew, and anterior resection anastomosis. The differences all were statistically significant.

Among stage IV cases, mean operating time was longer in obliterated cul-de-sac cases (159 vs. 108 minutes), with higher blood loss, 100 mL versus 50 mL.

“Patients with obliterated cul-de-sacs identified intraoperatively should be referred to minimally invasive gynecologic surgeons because of the ... extra training required to safely perform [laparoscopic hysterectomy] with limited morbidity,” said lead investigator Alexandra Melnyk, MD, a University of Pittsburgh ob.gyn resident.

There was no industry funding and the investigators reported no disclosures.

aotto@mdedge.com

SOURCE: Melnyk A et al. 2018 AAGL Global Congress, Abstract 81.

LAS VEGAS – When stage IV endometriosis with obliterated posterior cul-de-sac is discovered during laparoscopic hysterectomy, or suspected beforehand, women should be referred to a minimally invasive gynecologic surgery specialist because the procedure will be much more difficult, investigators said at the meeting sponsored by AAGL.

M. Alexander Otto/MDedge News

They reviewed 333 laparoscopic hysterectomies where endometriosis was discovered in the operating room. The disease is known to increase the complexity of hysterectomy; the investigators wanted to quantify the risk by endometriosis severity. Among their subjects, 237 women (71%) had stage I, II, or III endometriosis; 96 (29%) had stage IV disease, including 55 women (57%) with obliterated posterior cul-de-sacs.

Surgery was longer among stage IV cases (137 vs. 116 minutes), and there was greater blood loss; 66% of stage IV women required laparoscopic-modified radical hysterectomy versus about a quarter of women with stage I-III endometriosis.

Laparoscopic hysterectomy was even more complex when women with stage IV endometriosis had obliterated cul-de-sacs. A total of 93% required modified radical hysterectomies versus 29% of stage IV women with intact cul-de-sacs. Additional procedures were far more likely in this population, including salpingectomy, ureterolysis, enterolysis, cystoscopy, ureteral stenting, proctoscopy, bowel oversew, and anterior resection anastomosis. The differences all were statistically significant.

Among stage IV cases, mean operating time was longer in obliterated cul-de-sac cases (159 vs. 108 minutes), with higher blood loss, 100 mL versus 50 mL.

“Patients with obliterated cul-de-sacs identified intraoperatively should be referred to minimally invasive gynecologic surgeons because of the ... extra training required to safely perform [laparoscopic hysterectomy] with limited morbidity,” said lead investigator Alexandra Melnyk, MD, a University of Pittsburgh ob.gyn resident.

There was no industry funding and the investigators reported no disclosures.

aotto@mdedge.com

SOURCE: Melnyk A et al. 2018 AAGL Global Congress, Abstract 81.

LAS VEGAS – There hasn’t been a single corneal abrasion in 860 cases of gynecologic robotic surgery at the University of Texas, Austin, since surgeons and anesthesiologists there started sealing women’s eyes shut with a thick layer of ointment and Tegaderm, instead of the usual small squeeze of ointment and tape, according to Michael T. Breen, MD, a gynecologic surgeon at the university.

M. Alexander Otto/MDedge News

Slathered eyes and Tegaderm are now standard practice at the university. Before the switch was made, there were six corneal abrasions in 231 cases over 6 months. Two of those patients stayed longer in the hospital than they would have otherwise. The changes have eliminated the problem.

The impetus for the switch was a 42-year-old woman who had a robotic hysterectomy. The surgery went fine, but then Dr. Breen had to rush back to the recovery room. The woman was screaming in pain, not from her surgery, but from her left eye.

Corneal abrasions are a well-known risk of surgery because anesthesia decreases tear production and dries the eyes. Robotic gynecologic surgery increases the risk even more, because patients are under longer than with other approaches, and the steep Trendelenburg increases intraocular pressure and eye edema, especially with excess IV fluid.

And “believe it or not, having a pulse oximeter on the dominant hand [also] increases your risk of ocular injury,” Dr. Breen said. Sometimes, patients wake up, go to rub their eyes, and drag the device across their cornea, he said.

The screaming patient – who recovered without permanent damage – prompted Dr. Breen and his colleagues to turn to the literature for solutions. “One was a fully occlusive eye dressing, more than the tape we’ve all been accustomed to, with thick eye ointment application and Tegaderm applying positive pressure to the eye,” he said.

Dr. Michael Breen/University of Texas, Austin

Dr. Breen showed his audience a slide of the setup. “It looks a little unorthodox, but this is how every one of our robotic patients now have their eyes protected. Thick gel which is then covered with a positive pressure Tegaderm,” he said.

Another change was telling patients to keep their hands off their eyes for the first few postop hours, and placing the pulse ox on the nondominant hand. The team already had been decreasing IV fluids as part of their enhanced recovery after surgery protocol, and bringing patients out of steep Trendelenburg as soon as possible.

With the changes, “the rate of corneal abrasions decreased from 2.6% to 0% – and has stayed there,” Dr. Breen said.

There’ve been no allergic reactions to Tegaderm and no eyelid problems. “What we have seen with the simple taping is that, when it comes off, so does some of the eyelid, particularly with geriatric patients. We have not seen that with Tegaderm,” he said.

“Some people use goggles to protect the eyes, and we thought initially that the camera was hitting the face, so we used the Mayo stand to protect it from the camera,” but that didn’t turn out to be the problem, he said. “Goggles actually may make things worse.”

The project had no industry funding, and Dr. Breen had no relevant disclosures.

aotto@mdedge.com
 

SOURCE: Breen MT et al. 2018 AAGL Global Congress, Abstract 16.

LAS VEGAS – There hasn’t been a single corneal abrasion in 860 cases of gynecologic robotic surgery at the University of Texas, Austin, since surgeons and anesthesiologists there started sealing women’s eyes shut with a thick layer of ointment and Tegaderm, instead of the usual small squeeze of ointment and tape, according to Michael T. Breen, MD, a gynecologic surgeon at the university.

M. Alexander Otto/MDedge News

Slathered eyes and Tegaderm are now standard practice at the university. Before the switch was made, there were six corneal abrasions in 231 cases over 6 months. Two of those patients stayed longer in the hospital than they would have otherwise. The changes have eliminated the problem.

The impetus for the switch was a 42-year-old woman who had a robotic hysterectomy. The surgery went fine, but then Dr. Breen had to rush back to the recovery room. The woman was screaming in pain, not from her surgery, but from her left eye.

Corneal abrasions are a well-known risk of surgery because anesthesia decreases tear production and dries the eyes. Robotic gynecologic surgery increases the risk even more, because patients are under longer than with other approaches, and the steep Trendelenburg increases intraocular pressure and eye edema, especially with excess IV fluid.

And “believe it or not, having a pulse oximeter on the dominant hand [also] increases your risk of ocular injury,” Dr. Breen said. Sometimes, patients wake up, go to rub their eyes, and drag the device across their cornea, he said.

The screaming patient – who recovered without permanent damage – prompted Dr. Breen and his colleagues to turn to the literature for solutions. “One was a fully occlusive eye dressing, more than the tape we’ve all been accustomed to, with thick eye ointment application and Tegaderm applying positive pressure to the eye,” he said.

Dr. Michael Breen/University of Texas, Austin

Dr. Breen showed his audience a slide of the setup. “It looks a little unorthodox, but this is how every one of our robotic patients now have their eyes protected. Thick gel which is then covered with a positive pressure Tegaderm,” he said.

Another change was telling patients to keep their hands off their eyes for the first few postop hours, and placing the pulse ox on the nondominant hand. The team already had been decreasing IV fluids as part of their enhanced recovery after surgery protocol, and bringing patients out of steep Trendelenburg as soon as possible.

With the changes, “the rate of corneal abrasions decreased from 2.6% to 0% – and has stayed there,” Dr. Breen said.

There’ve been no allergic reactions to Tegaderm and no eyelid problems. “What we have seen with the simple taping is that, when it comes off, so does some of the eyelid, particularly with geriatric patients. We have not seen that with Tegaderm,” he said.

“Some people use goggles to protect the eyes, and we thought initially that the camera was hitting the face, so we used the Mayo stand to protect it from the camera,” but that didn’t turn out to be the problem, he said. “Goggles actually may make things worse.”

The project had no industry funding, and Dr. Breen had no relevant disclosures.

aotto@mdedge.com
 

SOURCE: Breen MT et al. 2018 AAGL Global Congress, Abstract 16.

LAS VEGAS – There hasn’t been a single corneal abrasion in 860 cases of gynecologic robotic surgery at the University of Texas, Austin, since surgeons and anesthesiologists there started sealing women’s eyes shut with a thick layer of ointment and Tegaderm, instead of the usual small squeeze of ointment and tape, according to Michael T. Breen, MD, a gynecologic surgeon at the university.

M. Alexander Otto/MDedge News

Slathered eyes and Tegaderm are now standard practice at the university. Before the switch was made, there were six corneal abrasions in 231 cases over 6 months. Two of those patients stayed longer in the hospital than they would have otherwise. The changes have eliminated the problem.

The impetus for the switch was a 42-year-old woman who had a robotic hysterectomy. The surgery went fine, but then Dr. Breen had to rush back to the recovery room. The woman was screaming in pain, not from her surgery, but from her left eye.

Corneal abrasions are a well-known risk of surgery because anesthesia decreases tear production and dries the eyes. Robotic gynecologic surgery increases the risk even more, because patients are under longer than with other approaches, and the steep Trendelenburg increases intraocular pressure and eye edema, especially with excess IV fluid.

And “believe it or not, having a pulse oximeter on the dominant hand [also] increases your risk of ocular injury,” Dr. Breen said. Sometimes, patients wake up, go to rub their eyes, and drag the device across their cornea, he said.

The screaming patient – who recovered without permanent damage – prompted Dr. Breen and his colleagues to turn to the literature for solutions. “One was a fully occlusive eye dressing, more than the tape we’ve all been accustomed to, with thick eye ointment application and Tegaderm applying positive pressure to the eye,” he said.

Dr. Michael Breen/University of Texas, Austin

Dr. Breen showed his audience a slide of the setup. “It looks a little unorthodox, but this is how every one of our robotic patients now have their eyes protected. Thick gel which is then covered with a positive pressure Tegaderm,” he said.

Another change was telling patients to keep their hands off their eyes for the first few postop hours, and placing the pulse ox on the nondominant hand. The team already had been decreasing IV fluids as part of their enhanced recovery after surgery protocol, and bringing patients out of steep Trendelenburg as soon as possible.

With the changes, “the rate of corneal abrasions decreased from 2.6% to 0% – and has stayed there,” Dr. Breen said.

There’ve been no allergic reactions to Tegaderm and no eyelid problems. “What we have seen with the simple taping is that, when it comes off, so does some of the eyelid, particularly with geriatric patients. We have not seen that with Tegaderm,” he said.

“Some people use goggles to protect the eyes, and we thought initially that the camera was hitting the face, so we used the Mayo stand to protect it from the camera,” but that didn’t turn out to be the problem, he said. “Goggles actually may make things worse.”

The project had no industry funding, and Dr. Breen had no relevant disclosures.

aotto@mdedge.com
 

SOURCE: Breen MT et al. 2018 AAGL Global Congress, Abstract 16.

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

aotto@mdedge.com

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

aotto@mdedge.com

LAS VEGAS – Single-port robotic sacrocolpopexy has the same learning curve as the multiport procedure – 15 cases, according to Israeli investigators.

M. Alexander Otto/MDedge News

Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.

The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.

They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.

It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).

With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.

Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.

There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.

There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m², and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.

There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.

aotto@mdedge.com

Shock waves moved through the gynecologic oncology world on Oct. 31, 2018, when the New England Journal of Medicine published two papers on survival outcomes for women undergoing surgery for early stage cervical cancer.

The first was a randomized controlled trial of laparotomy and minimally invasive surgery (MIS) for radical hysterectomy called the LACC trial.¹ In the multicenter, international trial of 631 women, the primary objective was disease-specific survival (cervical cancer–related deaths) and was powered to detect noninferiority of the MIS approach when compared with laparotomy. The trial was closed early when investigators noted a lower than expected rate of 3-year, disease-free survival (91% vs. 97%) from cervical cancer in the MIS group, which was made up of 84% laparoscopic and 16% robotic approaches, versus laparotomy. There were 19 deaths in the MIS group observed versus three in the laparotomy group. The conclusions of the trial were that MIS surgery is associated with inferior cervical cancer survival.

In the second study, authors analyzed data from large U.S. databases – the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program – to collect all-cause mortality for patients with early-stage cervical cancer who had undergone radical hysterectomy during 2010-2013.² Among 2,461 observed results, 1,225 had undergone MIS surgery with the majority (79.8%) via robotic-assistance. Women undergoing MIS approaches had smaller, lower grade tumors; were more likely to be white, privately insured, and of a higher income; and had surgery later in the cohort and by nonacademic centers. The researchers adjusted for risk factors with an analytic process called propensity-score weighting, which matched the groups more closely in an attempt to minimize confounders. They identified higher all-cause mortality among women who were treated with an MIS approach, compared with those treated with laparotomy (hazard ratio, 1.65). They also observed a significant decline in the survival from cervical cancer annually that corresponded to the uptake of MIS radical hysterectomies.

In the wake of these publications, many concluded that gynecologic oncologists should no longer offer a minimally invasive approach for radical hysterectomy. Certainly level I evidence published in a highly influential journal is compelling, and the consistency in findings over two studies adds further weight to the results. However, was this the correct conclusion to draw from these results? Surgeons who had been performing MIS radical hysterectomies for many years with favorable outcomes are challenging this and are raising questions about external generalizability and whether these findings were driven by the surgery itself or by the surgeon.

The studies’ authors proposed hypotheses for their results that implicate the surgical route rather than the surgeon; however, these seem ad hoc and not well supported by data, including the authors’ own data. The first was the hypothesis that cervical tumors were being disrupted and disseminated through the use of uterine manipulators in MIS approaches. However, cervical cancers are fairly routinely “disrupted” by preoperative cone biopsies, loop electrosurgical excision procedures (LEEP), and sharp biopsies, which are arguably more invasive than placement of a manipulator. Uterine manipulators routinely are used in endometrial cancer surgeries, in which the manipulator is embedded within the tumor, without an associated negative survival effect in randomized trials.³ Additionally, not all surgeons utilize manipulators for radical hysterectomies, and these studies did not measure or report on their use; therefore, it is impossible to know whether, and by what magnitude, manipulators played a role. Finally, if uterine manipulators are the explanation for inferior survival, surely the recommendation should be to discourage their use, rather than abandon the MIS approach all together.

The other explanation offered was exposure of the tumor to CO₂ gas. This seems an even less plausible explanation because CO₂ gas is routinely used in MIS cancer surgeries for endometrial, prostate, gastric, and colorectal surgeries and is used as insufflation for malignant interventional endoscopies without a significant deleterious effect. Additionally, the cervix is not exposed to CO₂ until colpotomy at the procedure’s end – and only briefly. The in vitro studies implicating a negative effect of simulated CO₂ pneumoperitoneum are neither compelling nor consistent.^4,5

I would like to propose another hypothesis for the results: surgical proficiency. Surgery, unlike medical interventions, is not a simple variable that is dichotomous – performed or not. Surgeons do not randomly select operative approaches for patients. We select surgical approaches based on patients’ circumstances and surgeon factors, including our own mastery of the various techniques. Randomized surgical trials rely on the notion that a surgeon is equally skilled in both or all approaches offered, but this is clearly not the case, and any surgeon recognizes this if he or she has observed more than one surgeon or has attempted a procedure via different routes. While some procedures, such as extrafascial hysterectomy for endometrial cancer, are relatively straightforward and surgeon capabilities are more equitable across different approaches, cervical cancer surgery is quite different.

Early-stage cervical cancer primarily exerts radial growth into the cervical stroma and parametria. Curative surgical excision requires broadly negative margins through this tissue, a so called “radical hysterectomy.” The radicality of hysterectomy has been categorized in stages, acknowledging that different sized lesions require different volumes of parametrial resection to achieve adequate clearance from the tumor.⁶ In doing so, the surgeon must skeletonize and mobilize the distal ureters, cardinal ligament webs, and uterosacral ligaments. These structures are in close proximity to major vascular and neural structures. Hence, the radical hysterectomy is, without dispute, a technically challenging procedure.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at obnews@mdedge.com.
 

References

1. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395.

2. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1804923.

3. J Clin Oncol. 2012 Mar 1;30(7):695-700.

4. Med Sci Monit. 2014 Dec 1;20:2497-503.

5. Surg Endosc. 2006 Oct;20(10):1556-9.

6. Gynecol Oncol. 2011 Aug;122(2):264-8.

7. Surgery. 2016 Mar;159(3):736-48.

Shock waves moved through the gynecologic oncology world on Oct. 31, 2018, when the New England Journal of Medicine published two papers on survival outcomes for women undergoing surgery for early stage cervical cancer.

The first was a randomized controlled trial of laparotomy and minimally invasive surgery (MIS) for radical hysterectomy called the LACC trial.¹ In the multicenter, international trial of 631 women, the primary objective was disease-specific survival (cervical cancer–related deaths) and was powered to detect noninferiority of the MIS approach when compared with laparotomy. The trial was closed early when investigators noted a lower than expected rate of 3-year, disease-free survival (91% vs. 97%) from cervical cancer in the MIS group, which was made up of 84% laparoscopic and 16% robotic approaches, versus laparotomy. There were 19 deaths in the MIS group observed versus three in the laparotomy group. The conclusions of the trial were that MIS surgery is associated with inferior cervical cancer survival.

In the second study, authors analyzed data from large U.S. databases – the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program – to collect all-cause mortality for patients with early-stage cervical cancer who had undergone radical hysterectomy during 2010-2013.² Among 2,461 observed results, 1,225 had undergone MIS surgery with the majority (79.8%) via robotic-assistance. Women undergoing MIS approaches had smaller, lower grade tumors; were more likely to be white, privately insured, and of a higher income; and had surgery later in the cohort and by nonacademic centers. The researchers adjusted for risk factors with an analytic process called propensity-score weighting, which matched the groups more closely in an attempt to minimize confounders. They identified higher all-cause mortality among women who were treated with an MIS approach, compared with those treated with laparotomy (hazard ratio, 1.65). They also observed a significant decline in the survival from cervical cancer annually that corresponded to the uptake of MIS radical hysterectomies.

In the wake of these publications, many concluded that gynecologic oncologists should no longer offer a minimally invasive approach for radical hysterectomy. Certainly level I evidence published in a highly influential journal is compelling, and the consistency in findings over two studies adds further weight to the results. However, was this the correct conclusion to draw from these results? Surgeons who had been performing MIS radical hysterectomies for many years with favorable outcomes are challenging this and are raising questions about external generalizability and whether these findings were driven by the surgery itself or by the surgeon.

The studies’ authors proposed hypotheses for their results that implicate the surgical route rather than the surgeon; however, these seem ad hoc and not well supported by data, including the authors’ own data. The first was the hypothesis that cervical tumors were being disrupted and disseminated through the use of uterine manipulators in MIS approaches. However, cervical cancers are fairly routinely “disrupted” by preoperative cone biopsies, loop electrosurgical excision procedures (LEEP), and sharp biopsies, which are arguably more invasive than placement of a manipulator. Uterine manipulators routinely are used in endometrial cancer surgeries, in which the manipulator is embedded within the tumor, without an associated negative survival effect in randomized trials.³ Additionally, not all surgeons utilize manipulators for radical hysterectomies, and these studies did not measure or report on their use; therefore, it is impossible to know whether, and by what magnitude, manipulators played a role. Finally, if uterine manipulators are the explanation for inferior survival, surely the recommendation should be to discourage their use, rather than abandon the MIS approach all together.

The other explanation offered was exposure of the tumor to CO₂ gas. This seems an even less plausible explanation because CO₂ gas is routinely used in MIS cancer surgeries for endometrial, prostate, gastric, and colorectal surgeries and is used as insufflation for malignant interventional endoscopies without a significant deleterious effect. Additionally, the cervix is not exposed to CO₂ until colpotomy at the procedure’s end – and only briefly. The in vitro studies implicating a negative effect of simulated CO₂ pneumoperitoneum are neither compelling nor consistent.^4,5

I would like to propose another hypothesis for the results: surgical proficiency. Surgery, unlike medical interventions, is not a simple variable that is dichotomous – performed or not. Surgeons do not randomly select operative approaches for patients. We select surgical approaches based on patients’ circumstances and surgeon factors, including our own mastery of the various techniques. Randomized surgical trials rely on the notion that a surgeon is equally skilled in both or all approaches offered, but this is clearly not the case, and any surgeon recognizes this if he or she has observed more than one surgeon or has attempted a procedure via different routes. While some procedures, such as extrafascial hysterectomy for endometrial cancer, are relatively straightforward and surgeon capabilities are more equitable across different approaches, cervical cancer surgery is quite different.

Early-stage cervical cancer primarily exerts radial growth into the cervical stroma and parametria. Curative surgical excision requires broadly negative margins through this tissue, a so called “radical hysterectomy.” The radicality of hysterectomy has been categorized in stages, acknowledging that different sized lesions require different volumes of parametrial resection to achieve adequate clearance from the tumor.⁶ In doing so, the surgeon must skeletonize and mobilize the distal ureters, cardinal ligament webs, and uterosacral ligaments. These structures are in close proximity to major vascular and neural structures. Hence, the radical hysterectomy is, without dispute, a technically challenging procedure.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at obnews@mdedge.com.
 

References

1. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395.

2. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1804923.

3. J Clin Oncol. 2012 Mar 1;30(7):695-700.

4. Med Sci Monit. 2014 Dec 1;20:2497-503.

5. Surg Endosc. 2006 Oct;20(10):1556-9.

6. Gynecol Oncol. 2011 Aug;122(2):264-8.

7. Surgery. 2016 Mar;159(3):736-48.

Shock waves moved through the gynecologic oncology world on Oct. 31, 2018, when the New England Journal of Medicine published two papers on survival outcomes for women undergoing surgery for early stage cervical cancer.

The first was a randomized controlled trial of laparotomy and minimally invasive surgery (MIS) for radical hysterectomy called the LACC trial.¹ In the multicenter, international trial of 631 women, the primary objective was disease-specific survival (cervical cancer–related deaths) and was powered to detect noninferiority of the MIS approach when compared with laparotomy. The trial was closed early when investigators noted a lower than expected rate of 3-year, disease-free survival (91% vs. 97%) from cervical cancer in the MIS group, which was made up of 84% laparoscopic and 16% robotic approaches, versus laparotomy. There were 19 deaths in the MIS group observed versus three in the laparotomy group. The conclusions of the trial were that MIS surgery is associated with inferior cervical cancer survival.

In the second study, authors analyzed data from large U.S. databases – the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program – to collect all-cause mortality for patients with early-stage cervical cancer who had undergone radical hysterectomy during 2010-2013.² Among 2,461 observed results, 1,225 had undergone MIS surgery with the majority (79.8%) via robotic-assistance. Women undergoing MIS approaches had smaller, lower grade tumors; were more likely to be white, privately insured, and of a higher income; and had surgery later in the cohort and by nonacademic centers. The researchers adjusted for risk factors with an analytic process called propensity-score weighting, which matched the groups more closely in an attempt to minimize confounders. They identified higher all-cause mortality among women who were treated with an MIS approach, compared with those treated with laparotomy (hazard ratio, 1.65). They also observed a significant decline in the survival from cervical cancer annually that corresponded to the uptake of MIS radical hysterectomies.

In the wake of these publications, many concluded that gynecologic oncologists should no longer offer a minimally invasive approach for radical hysterectomy. Certainly level I evidence published in a highly influential journal is compelling, and the consistency in findings over two studies adds further weight to the results. However, was this the correct conclusion to draw from these results? Surgeons who had been performing MIS radical hysterectomies for many years with favorable outcomes are challenging this and are raising questions about external generalizability and whether these findings were driven by the surgery itself or by the surgeon.

The studies’ authors proposed hypotheses for their results that implicate the surgical route rather than the surgeon; however, these seem ad hoc and not well supported by data, including the authors’ own data. The first was the hypothesis that cervical tumors were being disrupted and disseminated through the use of uterine manipulators in MIS approaches. However, cervical cancers are fairly routinely “disrupted” by preoperative cone biopsies, loop electrosurgical excision procedures (LEEP), and sharp biopsies, which are arguably more invasive than placement of a manipulator. Uterine manipulators routinely are used in endometrial cancer surgeries, in which the manipulator is embedded within the tumor, without an associated negative survival effect in randomized trials.³ Additionally, not all surgeons utilize manipulators for radical hysterectomies, and these studies did not measure or report on their use; therefore, it is impossible to know whether, and by what magnitude, manipulators played a role. Finally, if uterine manipulators are the explanation for inferior survival, surely the recommendation should be to discourage their use, rather than abandon the MIS approach all together.

The other explanation offered was exposure of the tumor to CO₂ gas. This seems an even less plausible explanation because CO₂ gas is routinely used in MIS cancer surgeries for endometrial, prostate, gastric, and colorectal surgeries and is used as insufflation for malignant interventional endoscopies without a significant deleterious effect. Additionally, the cervix is not exposed to CO₂ until colpotomy at the procedure’s end – and only briefly. The in vitro studies implicating a negative effect of simulated CO₂ pneumoperitoneum are neither compelling nor consistent.^4,5

I would like to propose another hypothesis for the results: surgical proficiency. Surgery, unlike medical interventions, is not a simple variable that is dichotomous – performed or not. Surgeons do not randomly select operative approaches for patients. We select surgical approaches based on patients’ circumstances and surgeon factors, including our own mastery of the various techniques. Randomized surgical trials rely on the notion that a surgeon is equally skilled in both or all approaches offered, but this is clearly not the case, and any surgeon recognizes this if he or she has observed more than one surgeon or has attempted a procedure via different routes. While some procedures, such as extrafascial hysterectomy for endometrial cancer, are relatively straightforward and surgeon capabilities are more equitable across different approaches, cervical cancer surgery is quite different.

Early-stage cervical cancer primarily exerts radial growth into the cervical stroma and parametria. Curative surgical excision requires broadly negative margins through this tissue, a so called “radical hysterectomy.” The radicality of hysterectomy has been categorized in stages, acknowledging that different sized lesions require different volumes of parametrial resection to achieve adequate clearance from the tumor.⁶ In doing so, the surgeon must skeletonize and mobilize the distal ureters, cardinal ligament webs, and uterosacral ligaments. These structures are in close proximity to major vascular and neural structures. Hence, the radical hysterectomy is, without dispute, a technically challenging procedure.

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no conflicts of interest. Email Dr. Rossi at obnews@mdedge.com.
 

References

1. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395.

2. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1804923.

3. J Clin Oncol. 2012 Mar 1;30(7):695-700.

4. Med Sci Monit. 2014 Dec 1;20:2497-503.

5. Surg Endosc. 2006 Oct;20(10):1556-9.

6. Gynecol Oncol. 2011 Aug;122(2):264-8.

7. Surgery. 2016 Mar;159(3):736-48.