Author Insights: Cancer Risks of Uterine Procedure Probed

Jason D. Wright, MD, of Columbia University College of Physicians and Surgeons, and colleagues found that 1 in 386 women who undergo morcellation for uterine fibroids have undetected uterine cancer. Morcellation may inadvertently spread cancerous tissue throughout the abdomen. Image: Columbia University

Jason D. Wright, MD, of Columbia University College of Physicians and Surgeons, and colleagues found that 1 in 368 women who undergo morcellation for uterine fibroids have undetected uterine cancer. Morcellation may inadvertently spread cancerous tissue throughout the abdomen. Image: Columbia University

More than 1 in 360 women who undergo a surgical procedure to treat noncancerous growths called fibroids that develop from the muscular tissue of the uterus have underlying cancer that may spread as a result of the surgery, suggests a study published in JAMA today.

A minimally invasive procedure to treat fibroids by removing the uterus, laparoscopic hysterectomy, involves use of electric or power morcellators to cut uterine tissue into pieces small enough to be removed through small incisions. This approach to treating uterine fibroids spares women the need for more invasive surgery, which involves longer recovery times. But there has been increasing concern that this less invasive procedure also may inadvertently spread cancerous tissue throughout the abdomen of women who have undiagnosed uterine cancer. Spreading such cancerous tissue can “upstage” the cancer and may lead to worse outcomes. Recently, a JAMA Viewpoint and JAMA news article outlined the concern and the need to apprise women of the benefits and risks of the procedure.

In April, the US Food and Drug Administration (FDA) warned against using morcellation to treat fibroids because of the potential risks. At the time, the agency estimated that 1 in 350 women who undergo surgical treatment for fibroids have undetected uterine cancer. Today’s study bolstered the FDA’s estimate.

The study examined records for 232 882 women who underwent a minimally invasive hysterectomy, including 36 470 (15.7%) whose surgery involved morcellation. The researchers found 99 cases of uterine cancer among the women who underwent morcellation, suggesting a prevalence of 1 cancer per every 368 women. Older women were at greater risk than those younger than 40 years of having underlying cancer.

Jason D. Wright, MD, chief of the division of gynecologic oncology and associate professor at Columbia University College of Physicians and Surgeons, discussed the findings with news@JAMA.

news@JAMA: Why did you decide to do the study?

Dr Wright: Once the controversy about electric power morcellation for uterine fibroids started to grow, we looked at the available data. We found little data describing the risks of underlying cancer in women undergoing morcellation.

news@JAMA: How do your findings compare with other studies?

Dr Wright: Most of the prior studies were not specific to morcellation. They just looked at cancer rates among those undergoing hysterectomy. Our study looked specifically at patients undergoing morcellation and found that the risk of having an underlying uterine cancer was 1 in 368. It’s fairly consistent with what the FDA estimated.

news@JAMA: What do your findings add to the current debate about the risks of morcellation?

Dr Wright: It’s one of the first large-scale studies looking at power morcellation. It provides a national estimate of the risk of morcellation. It’s important information for patients and clinicians so they can gauge the risks and benefits. We also looked at precancerous changes in the uterus and the risk factors and predictors of cancer. Age was a strong risk factor. If you are older, you are much more likely to have an underlying cancer.

news@JAMA: About a week ago, an FDA advisory panel concluded there is unlikely to be any way to reduce the cancer-associated risks of morcellation. What’s your reaction to that?

Dr Wright: Our study didn’t specifically address the risk of spreading cancer. The question is, if you undergo morcellation, how much does it increase your risk? Does it affect survival? There is not much objective data about techniques to reduce morcellation risk.

news@JAMA: What do you think women and physicians should know?

Dr Wright: The most important finding is that there is definitely a risk associated with underlying cancer or precancerous changes in women undergoing morcellation. It’s hard to detect prior to surgery. Morcellation may allow some women to undergo a minimally invasive surgery. Our study gives patients and physicians an estimate of the cancer risks so they can make an informed decision.

JAMA Forum: Women’s Rights Are Human Rights—Aren’t They?

Eli Adashi, MD, MS

Eli Adashi, MD, MS

So far, this summer has brought some interesting developments in the area of international women’s rights. Although precious few gains made it to the winning column, those that did were worth the wait. The common thread for these developments was Congress’s annual push-and-pull ritual in crafting the FY 2015 State and Foreign Operations Appropriations spending bill, which includes a large proportion of funding for US global health programs.

Here are some of the highlights.

Peace Corps Volunteers and Abortion Coverage

Since 1979, health coverage for Peace Corps volunteers has excluded coverage for abortions, even in the context of rape, incest, or when a pregnancy endangers a woman’s life. No other federal employees, and that includes Peace Corps employees, are similarly constrained. In a surprise move on June 24, the House Appropriations Committee approved an amendment to the House version of the State and Foreign Operations Appropriations spending bill (HR 5013) for next year, proposed by Rep Nita Lowey (D, NY), to remove this exclusion on Peace Corps volunteers in cases of rape, incest, and life endangerment.

This outcome could hardly have been anticipated. The House Appropriations Committee’s actions followed in the footsteps of its Senate counterpart, which approved a comparable measure on June 19 within the framework of its version of the spending bill (S 2499). The amendment, previously introduced as a stand-alone bill known as the Peace Corps Equity Act of 2013(S 813), was reintroduced in the Senate in May by Sen Jeanne Shaheen (D, NH). Given the bicameral consensus on this matter, all indications are that the provisions in question will be deemed exempt from further negotiation between the chambers and that coverage for abortion in the face of rape, incest, or life endangerment will in all likelihood be available to Peace Corps volunteers when the appropriation legislation is enacted into law later this year.

Global Gag Rule

The Senate version of the State and Foreign Operations Appropriations spending bill (again inspired by an amendment proposed by Sen Shaheen) also included a provision to permanently repeal the 1984 “global gag rule,” also known as the Mexico City Policy. This requires US-funded foreign nongovernmental organizations (NGOs) to certify, as a condition for receiving family planning assistance, that they would not perform or promote abortion as a method of family planning, even with funds from another source. The policy further requires US-funded foreign NGOs to refrain from providing information, referrals, or access to legal abortion and from advocating for local laws that would legalize abortion or provide access to it.

The global gag rule is currently in a state of abeyance by dint of an Executive Order by President Obama. The amendment, which would permanently repeal the policy if signed into law, was approved in the Senate committee with a significant bipartisan margin of 19 to 11.

In contrast, the House Appropriations Committee unveiled a FY15 State and Foreign Operations Appropriations spending bill that would reinstate the global gag rule. As articulated under the provision titled “Limitations on Family Planning/Reproductive Health,” the House version of the appropriation bill “prohibits funds for population planning activities or other population assistance to foreign nongovernmental organizations that promote or perform abortion, with certain exceptions.” An amendment by Rep Barbara Lee (D, CA) to strike the global gag rule from the draft version of the House bill failed on a vote of 19 to 25. If past precedent is any indication of the final outcome, any and all language applicable to the global gag rule is likely to be deleted in the upcoming conference between House and Senate negotiators, as it has under previous Democratic administrations.

United Nations Population Fund

Congress also revisited, as it does annually, the multilateral funding of the United Nations Population Fund (UNFPA) to support the UNFPA’s quest to ensure universal access to reproductive health. In this context, the House’s version of the FY15 State and Foreign Operations Appropriations spending bill included a proviso stipulating “no funds for the United Nations Population Fund.” An amendment by Rep Rose DeLauro (D, Conn) to reverse the funding ban in the draft bill was defeated on a vote of 20 to 26.

In contrast, the Senate version of the spending bill resolved that $37.5 million “shall be made available for the United Nations Population Fund” subject to the condition that the “UNFPA does not fund abortions.” While the final resolution of this intercameral disagreement is far from certain, past precedents suggest that the UNFPA will live to be funded another year.

The time frame for the enactment of the House and Senate committee–approved bills remains to be determined. However, with only a limited number of days left on the legislative calendar before the new federal fiscal year (October 1, 2014) and with adjournment planned for the 2014 midterm November elections, floor action seems unlikely. More likely than not, an interim (if unresolved) version of bill will likely be incorporated into a “continuing resolution,” until such time that a lame duck session of Congress convenes after the election.

The arcane congressional debate on the funding of international women’s health services may come across as a surreal throwback to times long gone by. It is precisely this harsh if improbable reality which prompts one to wonder all over again: women’s rights are human rights—aren’t they?

***

About the author: Eli Y. Adashi, MD, MS (eli_adashi@brown.edu) is a professor of medical science and the former dean of medicine and biological sciences at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. A member of the Institute of Medicine, the Association of American Physicians, and the American Association for the Advancement of Science, Dr Adashi has focused his writing on domestic and global health policy at the nexus of medicine, law, ethics, and social justice. A former Franklin fellow, Dr Adashi served as a senior advisor on Global Women’s Health to the Secretary of State office of Global Women’s Issues during the first term of the Obama Administration.

About The JAMA Forum: JAMA has assembled a team of leading scholars, including health economists, health policy experts, and legal scholars, to provide expert commentary and insight into news that involves the intersection of health policy and politics, economics, and the law. Each JAMA Forum entry expresses the opinions of the author but does not necessarily reflect the views or opinions of JAMA, the editorial staff, or the American Medical Association. More information is available here and here.

 

Author Insights: Time to Take Sex Ed Online

A pair of JAMA authors argue that online sex education will help kids get good information when and where they need it. Image: © iStock.com/gloch

A pair of JAMA authors argue that online sex education will help teens get good information when and where they need it. Image: © iStock.com/gloch

It’s time for evidence-based sexual education to meet teens where they are—online, argue a pair of authors in a JAMA Viewpoint today.

Providing adolescents with factual information about sexual health in public schools, particularly information about contraception, remains controversial in the United States—a situation reflected in the larger ongoing debate in US society about public policy and contraception.

This debate is a long-standing one. A 1966 JAMA editorial (reprinted in JAMA Revisited), noted that the American Medical Association took a stand to support the provision of contraception as an essential part of comprehensive health care, noting that some legal barriers to contraceptive access had been removed and that certain religious groups had softened their position on contraception. Last week, nearly a half century later, the US Supreme Court’s rule to affirm the right of certain employers to forgo providing health coverage for contraception based on religious grounds set off renewed debate about the intersection of public policy, sexual health, and religious convictions.

One way that educators and public health organizations can sidestep the controversy and educate teens about sexual health is to leverage digital tools to make comprehensive sex education (including information about contraception) available online, argue Victor C. Strasburger, MD, of the department of pediatrics at the University of New Mexico School of Medicine and Sarah S. Brown, MSPH, of the National Campaign to Prevent Teen and Unplanned Pregnancy.

 Victor C. Strasburger, MD, of the University of New Mexico School of Medicine and Sarah S. Brown, MSPH, of the National Campaign to Prevent Teen and Unplanned Pregnancy, make a case for online sex education in JAMA. Image: University of New Mexico.


Victor C. Strasburger, MD, of the University of New Mexico School of Medicine and Sarah S. Brown, MSPH, of the National Campaign to Prevent Teen and Unplanned Pregnancy, make a case for online sex education in JAMA. Image: University of New Mexico.

Strasburger discussed the issue with news@JAMA.

news@JAMA: What is the current state of sex education in the United States?

Dr Strasburger: Sex education has been controversial since I was a teen, and it really shouldn’t be. We really do a terrible job of educating kids about sex. Every other western country knows that teaching kids about sex makes them more knowledgeable. Some people think teaching them comprehensively will make them more sexually active, which isn’t true.

Teens get a lot of sex “education” from the media, which doesn’t provide good information about preventing pregnancy and the spread of sexually transmitted disease. It’s foolish to think 1 semester in middle school or high school can counteract the 15 000 sexual references they will see in the media each year.

We’ve come a long way with drug abuse prevention and bullying. But we haven’t made a lot of progress with sex education since I was growing up in the ’60s and ’70s.

news@JAMA: What are the advantages of online sex ed?

Dr Strasburger: The primary advantage is you don’t have to go through a conservative school board to get it implemented. The Internet offers free access to all. It’s also there 24/7. Teens need constant access to information about sexual health. They have questions that develop as situations arise. The Internet is always there. It’s a major resource that we have yet to use appropriately.

news@JAMA: What are the downsides?

Dr Strasburger: There’s a lot of bad information and pornography online. It’s unregulated. We worry that if health professionals create websites, they might be seen [by teens] as too totalitarian. You need teens involved in creating websites that are appealing. You can’t put a textbook online and expect it to be effective.

news@JAMA: How might local programs leverage online materials?

Dr Strasburger: We both feel the good will outweigh the bad if more people join in. It will give local communities more control. Communities vary in how conservative they are in their thinking. Communities can set up their own websites or text answer services.

The Internet can be a useful adjunct to traditional sex education. MTV has an app to identify the nearest place to find condoms. There is a website called bedsider.org that has good information and very funny videos. It takes the stigma out of teaching kids about sex.

news@JAMA: What’s your take-home message?

Dr Strasburger: Kids are getting a lot of sex education now, but it’s the wrong kind. We can use new technology wisely and in ways they will enjoy.

The controversy that exists around sex education is unnecessary and unscientific. There is no evidence that making kids smarter about sex makes them sexually active at a younger age. It’s time for the controversy to end.

Physicians Group Discourages Routine Pelvic Exam

A new guideline suggests women may skip the annual pelvic examination if they have no symptoms of concern. Image: © iStockphoto.com/jenjen42

A new guideline suggests women may skip the annual pelvic examination if they have no symptoms of concern. Image: © iStockphoto.com/jenjen42

Most women are accustomed to the uncomfortable ritual of having a yearly pelvic examination. But a new guideline from the American College of Physicians (ACP) suggests it may be time to make the procedure a thing of the past for women without any symptoms of concern. The recommendation does not apply to pregnant women or those who have signs of illness.

Women should continue to receive routine cervical cancer screening, according to the ACP, but the procedure should include only visual inspection and swabbing of the cervix, not a physical evaluation of the uterus. The ACP cautioned, however, that a pelvic examination is advisable for women who have vaginal discharge, abnormal bleeding, pain, urinary difficulties, or sexual dysfunction.

The recommendation is likely to be extremely controversial. The American College of Obstetricians and Gynecologists continues to recommend routine pelvic examinations as part of an annual well-woman visit. However, the ACP argues that there is no clear evidence of benefit, so the harms of fear, anxiety, embarrassment, pain, discomfort, and false positives outweigh the potential benefit of routinely conducting pelvic examinations on apparently healthy women.

The recommendation is based on the ACP’s review of the evidence on pelvic examinations from 1946 through 2014. The review found that pelvic examinations on apparently healthy women rarely detect noncervical cancer or other treatable conditions and that the practice didn’t improve patient outcomes.

“[Routine pelvic examination] rarely detects important disease and does not reduce mortality and is associated with discomfort for many women, false-positive and -negative examinations, and extra cost,” said Linda Humphrey, MD, a coauthor of the guideline.

An accompanying editorial noted that it’s not clear whether the ACP’s recommendation will change the practice of obstetrician/gynecologists. The editorialists note that the evidence base is limited and many gynecologists believe pelvic examinations help detect noncancerous masses, but they argue that clinicians should be aware of both the potential harms of pelvic examinations and the uncertainty surrounding benefits of the procedure.

Author Insights: Daily Vitamin C for Women Who Smoke During Pregnancy May Help Improve Lung Function of Their Children

Cindy McEvoy, MD, MCR of Oregon Health & Science University discusses the beneficial effects in women who smoke of taking vitamin C during pregnancy. Image from author.

Cindy McEvoy, MD, MCR of Oregon Health & Science University discusses the benefits of vitamin C supplementation for women who smoke during pregnancy. Image from author.

Though it’s well established that smoking during pregnancy is not good for fetal health, some women who smoke have difficulty quitting the habit during pregnancy. Now, according to new research, there may be a way to help protect the lung function of infants born to such women: a simple daily vitamin C pill.

The findings were described in a study released in JAMA in concert with its presentation at the American Thoracic Society meeting in San Diego on Sunday.

Researchers from Oregon Health & Science University in Portland randomly assigned a group of 179 pregnant women who smoked to receive either a daily 500 mg vitamin C pill or a placebo pill during the early stages of pregnancy. When the investigators assessed the newborns’ with standardized pulmonary function tests within 3 days of birth, they found that 2 important measures of lung function (the ratio of time to peak tidal expiratory flow to expiratory time and the passive respiratory compliance) were significantly better in newborns of mothers who took vitamin C compared with those who did not. At 1 year of age, however, these differences on pulmonary function tests were no longer significant.

However, at 1 year of age, the percentage of infants who had wheezing, as reported by their primary caregivers, was significantly different between the two groups: 15% in the vitamin C group vs 30% in the placebo group.

Lead author Cindy McEvoy, MD, MCR, discussed these findings with news@JAMA.

news@JAMA: Why did you conduct this study?

Dr McEvoy: Unfortunately, 50% of pregnant smokers are unable to quit smoking during pregnancy, and this has significant negative effects on the fetus, particularly on their future lung function and asthma risk. We had compelling preliminary data from studies in monkeys to support our hypothesis that daily vitamin C may help improve the babies’ lung function, and did this study to investigate this possibility.

news@JAMA: The primary measures of lung function that you found to be better in infants of the vitamin C group were the ratio of time to peak tidal expiratory flow to expiratory time, and the passive respiratory compliance. What do these measures actually mean in terms of how well the infants’ lungs are working?

Dr McEvoy: Basically, it means that the lungs are less stiff—in other words, more compliant. The small airways of the lungs are healthier, so it is easier to move air in and out when breathing. When moving air in and out of the small airways becomes difficult, wheezing occurs.

news@JAMA: Why did you no longer see a difference in lung function testing at 1 year of age? How do you explain the differences in wheezing observed at 1 year when there was no difference in lung function measures?

Dr McEvoy: One possibility for why we didn’t see differences in the 1-year pulmonary function tests is because we were only able to get this testing on about two-thirds of all the infants studied at delivery. Also, the pulmonary function tests at 1 year were done with the infants sedated, while the newborn tests were done with nonsedated infants. The use of passive respiratory mechanics at 1 year may have been less sensitive to detect lung function abnormalities. In terms of wheezing, we were able get this history from more than 90% of the patients studied at delivery, so that may have accounted for the differing results.

news@JAMA: Are you going to follow up these infants longer? What are the next steps for this research?

Dr McEvoy: Yes, we are currently getting follow-up respiratory histories on these infants. We are also doing additional studies looking at more sensitive pulmonary function tests, as well as some potential epigenetic changes caused by smoking during pregnancy that can be potentially prevented by vitamin C.

news@JAMA: Even though taking vitamin C during pregnancy seems to help with infant lung function at birth, you mention in your article that, importantly, it does not negate the other negative effects of smoking during pregnancy on newborn health. So what is the take-home message for pregnant smokers, based on this study?

Dr McEvoy: The ideal solution is still for pregnant smokers to quit smoking. But if they are unable to quit, vitamin C may be helpful for their infants’ lung function.

FDA Warns Against Procedure Used in Removing Fibroids

Image: JAMA, ©AMA

Image: JAMA, ©AMA

The US Food and Drug Administration (FDA) is discouraging the use of a surgical technique often used during minimally invasive surgery to treat uterine fibroids because it poses a risk of inadvertently spreading cancer cells from an undetected uterine tumor.

The focus of the agency’s concern is the use of medical devices called electric or power morcellators during laparoscopic (minimally invasive) surgery to remove the uterus or fibroids, noncancerous growths that develop from the muscular tissue of the uterus. The morcellator is used to cut uterine tissue into fragments that can be removed through the small incisions used in laparoscopic surgery. But in a safety communication released today, the FDA said that, based on its analysis of currently available data, 1 in 350 women who are treated for fibroids with surgery—a hysterectomy or myomectomy (fibroid removal)—is found to have an unsuspected uterine sarcoma, such as a leiomyosarcoma.

“If power morcellation is performed in women with unsuspected uterine sarcoma, there is a risk that the procedure will spread the cancerous tissue within the abdomen and pelvis, significantly worsening the patient’s likelihood of long-term survival,” the FDA said. “For this reason, and because there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma, the FDA discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids.”

As a JAMA news feature published earlier this year noted, in recent months, some critics of the procedure have said that use of the technique may be too risky, whereas others said that more research on risks was needed before banning it outright. The Society of Gynecologic Oncology issued a statement in December about the potential risks and the concern that no reliable methods exist to distinguish benign growths from cancers before they are removed. Some prominent US medical centers, including Brigham and Women’s Hospital, Massachusetts General Hospital, and the Cleveland Clinic issued statements stressing the importance of counseling patients about the procedure and potential risks.

An estimated 600 000 hysterectomies are performed annually in the United States. According to the National Institutes of Health, more than 200 000 hysterectomies are performed each year for uterine fibroids.

Various therapies, including drugs, surgical removal of individual fibroids, and hysterectomy, are used to treat symptoms caused by fibroids, which may include heavy or prolonged menstrual bleeding or pelvic pressure or pain. “Health care providers and patients should carefully consider available alternative treatment options for symptomatic uterine fibroids,” the FDA said.

***

For more information:

Critics of Fibroid Removal Procedure Question Risks It May Pose for Women With Undetected Uterine Cancer. Hampton, T. JAMA. 2014;311(9):891-893.

Evaluating the Risks of Electric Uterine Morcellation. Kho, KA and Nezhat, CH. JAMA. 2014;311(9):905-906.

 

 

 

 

 

 

 

 

 

 

 

New Tissue Engineering Studies Answer Important Questions

New research describes how 3-dimensional scaffolds were created to form engineered vaginal tissue. (Image: Wake Forest Institute for Regenerative Medicine)

New research describes how 3-dimensional scaffolds were created to form engineered vaginal tissue. (Image: Wake Forest Institute for Regenerative Medicine)

Researchers have for the first time used engineered tissue to successfully reconstruct noses and build implantable vaginas, according to 2 studies published today.

Reporting online in The Lancet, investigators at the University of Basel in Switzerland described reconstructive procedures on 5 patients aged 76 to 88 years with non-melanoma skin cancer on the nose. The patients had substantial amounts of skin and cartilage removed from the alar wings surrounding the nostrils. The tissue served as the basis to create grafts. Usually surgeons take grafts from the nasal septum, ear, or ribs to reconstruct the nose. But those procedures are invasive, painful, and may result in complications.

So the investigators developed an alternative method. They cultured patients’ nasal septum cartilage cells with growth factors for 2 weeks before seeding them onto collagen membranes. Culturing for 2 more weeks produced cartilage 40 times larger than the original biopsy. Grafts were individually shaped for each patient and implanted. One year after the reconstructions, all 5 patients were satisfied with their ability to breathe and their nose’s cosmetic appearance. None had any adverse effects.

“The engineered cartilage had clinical results comparable to the current standard surgery,” research team leader Ivan Martin, PhD, said in a statement. “The method opens the way to using engineered cartilage for more challenging reconstructions in facial surgery such as the complete nose, eyelid, or ear.”

The second study described techniques used to engineer laboratory-built vaginas for 4 teenage girls with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The condition is a rare genetic disorder in which the vagina and uterus don’t develop properly or at all.

Researchers in the United States and Mexico employed techniques similar to those used in the nose reconstructions. They extracted cells from each girl’s external genitals, expanded the cells, and seeded them onto biodegradable scaffolds sewn into 3-dimensional vagina-like shapes. The scaffolds were tailor-made for each girl.

Surgeons implanted the scaffolds by creating a canal in the pelvis and suturing the engineered vagina in place. After follow up for 8 years, the implants functioned the same as native vaginal tissue. All the patients’ responses to a Female Sexual Function Index questionnaire showed normal sexual function, including desire and pain-free intercourse. They reported no adverse effects.

In an accompanying editorial, researchers at University College London in England said the studies show that over time, the engineered tissues functioned the same as native tissue. The vaginal scaffold study also showed that the engineered tissues responded well as the girls developed into women and that the body’s own new blood vessel growth may be sufficient even for large engineered tissue structures.

“These authors have not only successfully treated several patients with a difficult clinical problem, but addressed some of the most important questions facing translation of tissue engineering technologies,” Martin Birchall, MD, one of the editorial’s coauthors, said in a statement.