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.

Increasing Lung Cancer Risk in 5 Minutes or Less

The sooner smokers light up after waking, the higher their risk of lung cancer, accordig to a new study. (Image: ©iStock.com/czekma13)

The sooner smokers light up after waking, the higher their risk of lung cancer, according to a new study. (Image: ©iStock.com/czekma13)

Smokers often crave a cigarette within minutes of waking, but a new study shows that lighting up immediately may increase their lung cancer risk.

Research published today in the Journal of the National Cancer Institute examined whether lung cancer risk is affected by how soon smokers have their first cigarette: within 5 minutes, from 6 to 30, 31 to 60, or more than 60 minutes after they wake up. The analysis is based on 3249 current or former smokers from a study in Italy; 1812 were patients with lung cancer and 1437 were control participants.

Of the participants with lung cancer, only 16% waited more than an hour for their first cigarette but 28% smoked within 5 minutes after waking. Among controls, about half didn’t smoke within the first hour after they awoke but 10% did so within 5 minutes.

Compared with waiting more than an hour, the risk of developing lung cancer increased by more than 2-fold among those who had their first cigarette either 6 to 30 or 31 to 60 minutes after waking. Among those who smoked within 5 minutes, the risk increased by 3.5-fold.

Increases in risk held up even after the researchers accounted for a number of factors, including sex, how long the participants had been smoking, how many cigarettes they smoked daily, lung tumor tissue structure, and whether or how long ago they had quit.

The researchers also analyzed similar data from a small number of smokers in a US cancer screening study. Results showed an increased lung cancer risk linked with how soon smokers had their first cigarette of the day, but the association was only borderline significant.

The study’s findings have clinical, public health, and research implications, the researchers noted. Having another way to evaluate risk could help improve lung cancer prediction models and the efficient use of spiral computerized tomography screening programs, they wrote.

Adding the time it takes smokers to have their first cigarette of the day to routine patient information on smoking “may also help smokers and clinicians better gauge lung cancer risk and thereby motivate smokers to quit,” the researchers noted.

Statin Use Can Stop When Illness Is Terminal, Study Reports

Patients whose life expectancy is less than a year can safely stop using statins, a new study reports. (Image: ©iStock.com/Gannet77)

Patients whose life expectancy is less than a year can safely stop using statins, a new study reports. (Image: ©iStock.com/Gannet77)

Discontinuing statin use in patients with late-stage cancer or other terminal illnesses isn’t harmful and may help improve patients’ quality of life, according to new research.

Data presented today at the American Society for Clinical Oncology’s annual meeting in Chicago show that ending statin use in patients with advanced diseases appears to offer several benefits. The study’s lead author, Jean Kutner, MD, MSPH, of the University of Colorado Cancer Center in Aurora, called research on when to stop preventive medications “a new line of investigation.”

Statins are among the most prescribed medications for their ability to lower cholesterol and reduce the risk of heart attack and stroke. About 40% of the drugs are prescribed to prevent a first heart attack or stroke and often patients take them for the rest of their lives.

Kutner and her colleagues with the Palliative Care Research Cooperative Group, which includes more than 20 US member institutions, enrolled 381 patients whose estimated life expectancy was 7 months. About half had cancer and all had taken a statin for at least 3 months. Two-thirds of the patients had taken a statin for more than 5 years.

Half of the patients were randomized to continue the drug, and the other half to stop taking it. Patients were monitored for up to a year to track cardiovascular events, changes in quality of life, and survival.

Death rates within 60 days were similar in both groups, about 20%. Rates of cardiovascular events were approximately 6% in each group. Median survival was 190 days among patients who continued taking a statin compared with 229 days among those who stopped the drug. Patients who quit statins had significant improvements in quality of life, especially in feelings of well-being and support. Stopping the drug also saves money.

Whether or when to stop preventive medications is an important issue in end-of-life care, the investigators noted. Some patients may start anticancer drugs or opioids for pain, increasing the risk of adverse events as their medications accumulate.

Kutner advised that patients with a life expectancy of less than 1 year who take a statin but haven’t recently had a heart attack or stroke talk with their physician about stopping the drug.

“One thing we found during the study was clinicians saying, ‘Hey, I never thought about stopping people’s statins,’ ” Kutner said in a statement. “Here’s a setting in which these drugs may not be doing most patients any good any more, and bringing up the subject of stopping unneeded medications offers the opportunity for shared decision making.”

Medications to prevent osteoporosis, blood clots, high blood pressure, and diabetes are candidates for future studies, Kutner added.

 

 

 

 

Vitamin D Deficiency May Be Linked With Aggressive Prostate Cancer

Vitamin D may be a biomarker of more aggressive prostate cancer, particularly in African American men. (Image: ©iStock.com/areeya_ann)

Vitamin D may be a biomarker of more aggressive prostate cancer, particularly in African American men. (Image: ©iStock.com/areeya_ann)

Vitamin D deficiency may increase the odds that some men who already are at high risk for prostate cancer will have an aggressive form of the disease, according to new research.

The study, published online today in Clinical Cancer Research, is the first to evaluate whether vitamin D deficiency might be associated with prostate cancer based on biopsy results from men who had abnormal findings on a prostate-specific antigen (PSA) test or digital rectal examination. Previous studies compared vitamin D levels only in men with or without prostate cancer.

Investigators enrolled 667 men aged 40 to 79 years who had their first prostate biopsy at 1 of 5 urology clinics in Chicago. About half were African American and the other half were European American. Their blood levels of 25-hydroxyvitamin D (25-OH D) were measured at enrollment to determine vitamin D deficiency.

European American men had higher 25-OH D levels (19.3 nanograms per milliliter [ng/mL] of blood) than African American men (16.7 ng/mL). Dark skin has more melanin, which blocks ultraviolent rays that trigger vitamin D production. The Institute of Medicine has concluded that a 25-OH D level below 12 ng/mL puts a person at risk for vitamin D deficiency and levels from 12 ng/mL to 20 ng/mL indicate insufficiency. But 20 ng/mL is considered adequate for most people.

Overall, 383 men in the study received a prostate cancer diagnosis. Among African American men, those with a 25-OH D level below 20 ng/mL were 2.4 times more likely to be diagnosed with prostate cancer than those with higher levels. African American men with 25-OH D levels below 12 mg/mL were nearly 5 times more likely to have aggressive prostate cancer and 4.2 times more likely to have a tumor stage T2b or higher, meaning that cancer is present in more than half of either the left or right side of the prostate.

Among European American men, 25-OH D levels weren’t related to overall prostate cancer risk. But those with levels below 12 ng/mL were 3.7 times more likely to have aggressive prostate cancer and 2.4 times more likely to have a tumor stage T2b or higher.

In both groups, low 25-OH D levels were linked with aggressive prostate cancer even after investigators accounted for diet, smoking habits, obesity, family medical history, and calcium intake.

“The stronger associations in African American men imply that vitamin D deficiency is a bigger contributor to prostate cancer in African American men compared with European American men,” lead author Adam Murphy, MD, said in a statement.

Murphy, an assistant professor of urology at Northwestern University’s Feinberg School of Medicine in Chicago, said vitamin D supplements may help prevent tumor progression in some men with prostate cancer. “It would be wise to be screened for vitamin D deficiency and treated,” he added.

Author Insights: Mammography False Positives Briefly Boost Anxiety

Anna N. A. Tosteson, ScD, of the Dartmouth Institute for Health Policy and Clinical Practice and Norris Cotton Center at the Geisel School of Medicine at Dartmouth, and colleagues found that false-positive mammography results elevate anxiety for women only briefly. Image: Dartmouth University

Anna N. A. Tosteson, ScD, of the Dartmouth Institute for Health Policy and Clinical Practice and Norris Cotton Center at the Geisel School of Medicine at Dartmouth, and colleagues found that false-positive mammography results elevate anxiety for women only briefly. Image: Norris Cotton Cancer Center

Women who receive a false-positive result from mammography screening may briefly experience elevated levels of anxiety, but the effect soon wears off, according to an analysis published today in JAMA Internal Medicine.

The relative risks and benefits of routine mammography screening for women have been debated for decades. Last fall, the debate took on renewed urgency as the US Preventive Services Task Force announced it would revisit its existing recommendations regarding mammography. The task force’s recommendations are influential and may affect whether health plans cover mammography.

The latest study results suggest that a temporary increase in anxiety may be one adverse effect of the false positives that inevitably result from screening.

To assess how false positives affect women and their attitudes toward future screening, Anna N. A. Tosteson, ScD, of the Dartmouth Institute for Health Policy and Clinical Practice and Norris Cotton Center at the Geisel School of Medicine at Dartmouth, and colleagues analyzed survey data from more than 1000 women who participated in the Digital Mammographic Imaging Screening Trial (DMIST). They found that anxiety was higher among women who received a false-positive result than among those who did not, but this difference didn’t persist at 1 year after screening. Women who had received a false positive were more likely to plan to have future mammograms than those who did not. Women who reported higher anxiety about potential future false-positive results were more likely to express willingness to stay overnight for testing that would reduce the risk of false positives, than those who did not report such anxiety.

Tosteson discussed the findings with news@JAMA.

news@JAMA: Why did you decide to conduct this study?

Dr Tosteson: At the time, the DMIST was launched it was thought that digital mammography wouldn’t be better at detecting cancer, but we thought it would be better at reducing false positives. We wanted to be able to value false positives when assessing the cost of digital mammography.

news@JAMA: Was digital better at avoiding false positives?

Dr Tosteson: In DMIST, there was no difference [in false positives] between traditional and digital mammography screening. Other studies have found the false-positive rate is higher for some groups of women. But overall, there is not much difference between the 2 types of mammography. Now, nearly all mammograms in the United States are digital.

False positives are a fairly common experience for women participating in mammography.

news@JAMA: What did your study tell us about the effects of false positives on women?

Dr Tosteson: We found a measurable increase in personal anxiety that was time limited, but no difference in general well-being. This suggests false-positive exams cause anxiety that is time limited. This anxiety didn’t negatively influence women’s future screening preferences. That result seems to be a little surprising.

news@JAMA: How do these results compare with other studies?

Dr Tosteson: Ours was unique in that it used a measure of well-being used by economists. The measures we used were generally not cancer-related per se. Some of the studies that have found long-term anxiety after a false positive looked at cancer-specific concerns.

news@JAMA: What are the implications for physicians counseling women or for women considering mammograms?

Dr Tosteson: Women need to understand how common the false-positive mammogram experience is. We found elevated anxiety to be a time-limited effect of false-positive test results. Our study did make it clear that women would generally prefer tests not associated with false positives, but there were limits on how far they were willing to go to get such a test. The results could be a little reassuring to women.

At the same time, I think the results have some value for people doing economic evaluations of breast screening. These evaluations include the impact of mammography on quality of life. Our study showed false-positive mammograms don’t really impact quality of life in a measurable way.

news@JAMA: What do you think is the main take-home message from your results?

Dr Tosteson: With all the controversy about mammography screenings, women need to be educated about the benefits and harms. It’s going to come down to how individual women balance the harms and benefits. It does come down to a preference-sensitive decision.Our findings would certainly not make screening less cost effective for 40- to 49-year-olds, or 50- to 59-year-olds.

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.

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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.