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Top News arrow Clinical Trials arrow Women's Breasts Riddled With Metal by Mistake in a Study
Women's Breasts Riddled With Metal by Mistake in a Study Print E-mail
Monday, 21 March 2011

About 30 women who participated in a clinical trial have been left hundreds of particles of potentially hazardous metal in their breast by a faulty disk made of tungsten and silicone that was used to shield against radiation exposure.

The New York Times reports (below) that "The women who were exposed to the tungsten were taking part in a study of a radiation technique that some doctors predicted would be a big advance in the treatment of breast cancer."

The resulting metal particles left in the women's breasts were caused by a flaw in the design of a medical device, the Axxent FlexiShield Mini, which had been cleared by the agency in June 2009 in an abbreviated approval process that is used for devices that are considered equivalent to products already on the market.

That process, known as 510(k), takes less time than the procedure used to approve a new device, and it generally does not require tests on humans.

The FlexiShield Mini equipment was recalled last month. Neither its manufacturer nor the F.D.A. could explain what went wrong with the device.

One of the women who is affected, a psychologist, said it never occurred to  her that the equipment might be faulty, she said, because she knew that it had been approved by the F.D.A. She also trusted the doctor and hospital to ensure that the study was safe.

“I had this illusion, like most people do, that the F.D.A. wouldn’t allow this to happen,” she said. “I definitely feel like a lab rat now.”

It is an example of slip shod FDAapprovals. Indeed, one has to wonder about the competence of FDA officials who approved the Axxent Flexishield Mini, a $100 disk made of tungsten and silicone.

Karen Riley, a spokeswoman for the agency, said it was just beginning its review of the device and the recall. So far, she said, F.D.A. toxicologists had found no evidence that the tungsten was toxic or that patients were harmed.

FDA spokeswoman, is likely ignorant about the concerns about tungsten exposure in the military. FDA toxicologists had better examine the published studies documenting cause for concern about tungsten's Neurobehavioral effects and potential reproductive, neurobehavioral and systemic effects of tungsten (see abstracts below).

Whatever may be said about manufacturers' inadequate safety testing of medical devices used in humans, the FDA bears a major responsibility for its dereliction of duty: and its rush to approve inadequately tested drugs and medical devices which receive the seal of approval based on abbreviated, "expedited review."

 Vera Hassner Sharav

 

THE NEW YORK TIMES

Riddled With Metal by Mistake in a Study

By DENISE GRADY

March 21, 2011

Women participating in a study of patients with breast cancer have been inadvertently left with hundreds of tiny particles of the heavy metal tungsten in their breast tissue and chest muscles. The particles came from a device used during surgery. The device has since been recalled.

A patient who was left with tungsten in her breast after participating in a medical study.

It is not known if the metal is dangerous to health because relatively little research has been done on its long-term effects in the body. But it shows up on mammograms, and may make them difficult to read, an especially troubling effect for women who have already had breast cancer and worry about recurrences. (The particles resemble calcium deposits, which can indicate cancer.)

About 30 women have been affected, according to the manufacturer of the device that caused the problem, the Axxent FlexiShield Mini. The women are in a quandary. At least one, fearing that the tungsten could cause cancer or another illness, is trying to decide whether to get rid of the particles by having her breast and its underlying tissue removed in a radical and disfiguring operation.

Twenty-seven of the cases occurred at Hoag Memorial Hospital Presbyterian in Newport Beach, Calif. Eleven of those women have had mammograms, and all 11 showed tungsten. Hospital officials declined interviews, but issued a statement acknowledging that the problem had occurred.

Two other women were treated in a study at Karmanos-Crittenton Cancer Center in Rochester Hills, Mich. A hospital spokeswoman said that both patients had been informed of the recall and the potential problem but had not returned to the hospital.

The episode casts doubt on the safeguards for people who participate in medical research and on the Food and Drug Administration’s ability to protect the public from flawed medical devices.

The Axxent FlexiShield Mini had been cleared by the agency in June 2009 in an abbreviated process used for devices that are considered equivalent to products already on the market. That process, known as 510(k), takes less time than the procedure used to approve a new device, and it generally does not require tests on humans. The FlexiShield Mini equipment was recalled last month. Neither its manufacturer nor the F.D.A. could explain what went wrong with the device.

Karen Riley, a spokeswoman for the agency, said it was just beginning its review of the device and the recall. So far, she said, F.D.A. toxicologists had found no evidence that the tungsten was toxic or that patients were harmed.

Ms. Riley said the 510(k) process was used to avoid “reinventing the wheel” for products that were essentially the same as others that had already passed muster with the agency.

The women who were exposed to the tungsten were taking part in a study of a radiation technique that some doctors predicted would be a big advance in the treatment of breast cancer. Unlike the usual five to seven weeks of daily radiation sessions, the newer method delivers the entire course of treatment in one dose while the woman is still in the operating room after undergoing a lumpectomy for breast cancer.

But in the study, a device that was temporarily placed in the women’s incisions during the radiation treatment was apparently flawed, and riddled their breasts with tungsten. The Axxent Flexishield Mini, a $100 disk made of tungsten and silicone, was used to shield healthy tissue from the radiation.

The first patient to take part in the study at Hoag said the events had shattered her faith in the vigilance of the drug agency, the hospital and her surgeon, who she said enthusiastically talked her into participating, emphasizing how convenient it would be to finish radiation treatment before she even woke from surgery.

“I do work, so it was appealing,” said the woman, a 57-year-old psychologist with a busy practice who did not want her name used for privacy reasons.

The purpose of the study was not to test the new radiation treatment itself, but rather to determine whether imaging studies could correctly predict which women would be candidates for it. The device’s manufacturer did not pay for the study.

It never occurred to the first patient that the equipment might be faulty, she said, because she knew that it had been approved by the F.D.A. She also trusted the doctor and hospital to ensure that the study was safe.

“I had this illusion, like most people do, that the F.D.A. wouldn’t allow this to happen,” she said. “I definitely feel like a lab rat now.”

The manufacturer, Xoft, which was bought in December by iCad, intended the shield to be used with its portable radiation device, the Axxent Electronic Brachytherapy System.

The president of iCad, Ken Ferry, said his company bought Xoft because the idea of giving radiation treatment during surgery seemed so promising. A study published last summer showed good results from a different radiation machine using the same technique. Mr. Ferry said he thought the procedure might eventually be used to treat half of the 270,000 women a year in the United States who develop breast cancer.

“We think the growth of the procedure will be dramatic over the next three years,” Mr. Ferry said. “That’s what really drove us to acquire the company.”

But iCad also acquired the tungsten problem, which became apparent only a week or two after the deal was closed.

“Dumb luck, if you want to use that word, is what it feels like to iCad that we ran into it,” Mr. Ferry said. But, he added, “it doesn’t diminish our enthusiasm.”

The psychologist is suing Hoag and the manufacturer.

She first learned that something was wrong in December, when she had a routine follow-up mammogram six months after her lumpectomy and radiation.

The image showed hundreds of tiny spots scattered inside her breast and along the muscle at the back of her chest wall. Doctors did not know what the spots were, but her radiologist said some resembled the calcifications that can indicate cancer. “I was terrified,” she said. “It looked like it was snowing inside my breast.”

A biopsy found the tungsten.

“I went to my oncologist,” she said. “He just was beside himself. He just said: ‘You’ve got to get this out of you. It’s toxic. You can’t have this in your system.’ ”

He urged her to have a mastectomy and recommended a surgeon, who told her that to remove the tungsten, he would have to remove her entire breast and some of the chest muscles.

“I would have a dent in my side,” she said. “He said he didn’t really want to move ahead until there was more information because it would be so disfiguring. That made me physically ill. I’d kind of gotten myself used to the idea of having a mastectomy, but not being disfigured.”

ICad has offered to pay for toxicology consultations for the exposed women, along with blood and urine tests to measure tungsten. The company has also said it will consider paying for mastectomies, and it commissioned a report to examine the scientific data on tungsten. The report said its toxicity appeared low, but that long-term studies were lacking.

Dr. Steven Markowitz, a physician at Queens College in New York who specializes in occupational and environmental medicine, said there was not much information about the effects of pure tungsten like that used in the shields. Most research, he said, involves workplace exposure to tungsten compounds.

“Given this unorthodox route of exposure, it’s hard to say a whole lot about likely consequences,” Dr. Markowitz said.

The first patient in the Hoag study said she had consulted a toxicologist, who told her little was known about the long-term health effects of tungsten but said that she (the toxicologist) would probably not leave it in her own body. The patient said that she was leaning toward having the surgery. But, she added, “I would love to hear there’s evidence that there’s nothing to worry about.”

 

~~~~~~~~~~~~~~~~~~~~ 
 

Neurotoxicol Teratol. 2008 Nov-Dec;30(6):455-61. Epub 2008 Jul 13.

Neurobehavioral effects of sodium tungstate exposure on rats and their progeny.

McInturf SM, Bekkedal MY, Wilfong E, Arfsten D, Gunasekar PG, Chapman GD.

Naval Health Research Center Detachment, Environmental Health Effects Laboratory, Wright Patterson Air Force Base, OH 45433, USA.

Abstract

The use of tungsten as a replacement for lead and depleted uranium in munitions began in the mid 1990's. Recent reports demonstrate tungsten solubilizes in soil and can migrate into drinking water supplies and therefore is a potential health risk to humans. This study evaluated the reproductive and neurobehavioral effects of sodium tungstate in Sprague-Dawley rats following 70 days of daily pre- and postnatal exposure. Adult male and female rats were orally dosed with diH(2)O vehicle, 5 or 125 mg/kg/day of sodium tungstate through mating, gestation, and weaning (PND 0-20). Daily administration of sodium tungstate produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distress vocalizations were elevated in the highest dose group. There was no treatment related effect on righting reflex latencies, however, the males had significantly shorter latencies than the females. Locomotor activity was affected in both the low and high dose groups of F0 females. Those in the low dose group showed increased distance traveled, more time in ambulatory movements, and less time in stereotypic behavior than controls or high dose animals. The high dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by sodium tungstate exposure and there were no apparent effects of treatment on F1 acoustic startle response or water maze navigation. Overall, the results of this study suggest pre- and postnatal oral exposure to sodium tungstate may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality. These findings warrant further investigation to characterize the neurotoxicity of sodium tungstate on dams and their developing pups.

~~~~~~~~~~~~  

Toxicol Appl Pharmacol. 2011 Feb 3. [Epub ahead of print]

The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats.

McInturf SM, Bekkedal MY, Wilfong E, Arfsten D, Chapman G, Gunasekar PG.

Naval Health Research Center Detachment, Environmental Health Effects Laboratory (NHRC/EHEL), Wright Patterson Air Force Base, OH.

Abstract

The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on matting success or offspring physical development. Distress vocalizations were elevated in F(1) offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females, however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F(1) females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P(0) animals of 125mg NaW dose group. The result of this study suggest pre and postnatal exposure to NaW may produced subtle neurobehavioral effects in offspring related to motor activity and emotionality.

Copyright © 2010. Published by Elsevier Inc.

 

 

 

 
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