Where Trilucent implants initially appeared significantly better than
saline or silicone implants, the UK (and other governments) have withdrawn
these medical devices from the marketplace and recommended removal of any
existing implants causing irritation.  Special emphasis is made that this
advice is precautionary. Although there have been reports of breast
swelling and discomfort in some women with these implants, there has been
no clinical evidence of any serious health problems, so far.

Telephone numbers (in the UK) for additional information:

    http://www.medical-devices.gov.uk/an1999(01).htm
    http://www.medical-devices.gov.uk/tbi-state.htm
    http://www.medical-devices.gov.uk/hn2000(05).htm

UK MEDICAL DEVICES AGENCY
STATEMENT ON THE SAFETY OF TRILUCENT BREAST IMPLANTS

In May 2000, the Medical Devices Agency (MDA) convened an Advisory Group
(consisting of toxicologists, plastic surgeons and a lay representative) to
consider new data on the safety of Trilucent breast implants. The Group
considered the available scientific evidence, made an assessment of the
risk to patients and, based on this assessment, provided advice to MDA.

Background.

Trilucent breast implants consist of a silicone elastomer shell with a
lipid filler based on soyabean oil. Over 9000 implants have been implanted
into almost 5,000 women in the UK.

In March 1999 the Medical Devices Agency (MDA) raised concerns about the
lack of long-term safety data on Trilucent breast implants particularly in
relation to the breakdown of the lipid filler. An independent view on the
relevant data was sought from four members of the Department of Health's
Committee of on Toxicity (COT) in March 1999. The COT members raised two
specific concerns at that time: the apparent irritation following rupture
and the apparent increase in levels of degradation products over that upon
which the manufacturer had undertaken their initial safety assessment. They
advised that further data should be obtained to allow a risk assessment to
be made. As a result of these concerns the company voluntarily withdrew
Trilucent breast implants (in March 1999) as a precautionary measure. MDA
also issued advice to the Health Service in the form of MDA Advice Notice
(AN1999(01)).

The Advice Notice stated that in 1999 there was no safety information to
suggest that removal of Trilucent breast implants was indicated but that
women should be advised to seek an immediate clinical consultation if they
noticed unusual breast swelling or inflammation associated with their
Trilucent breast implants.

New information.

After the March 1999 withdrawal from further sale of Trilucent breast
implants, MDA required the manufacturer to carry out further toxicological
testing on the filler used in Trilucent breast implants. The company has
now carried out chemical analyses which have established the general nature
and amount of breakdown products generated when the filler degrades.

The company had provided MDA with preliminary data on the levels of various
degradation products measured in samples obtained from both explanted
Trilucent breast implants and retained stock. The explant samples had not
been collected under controlled conditions. The samples from retained
implants were taken from devices which had been stored under the
manufacturer's recommended storage conditions.

The samples from the majority of the explants and retained implants
contained millimolar amounts of at least one type of aldehyde degradation
product. Other samples did not contain amounts greater than the limit of
detection of the measuring technique (10 micromolar). Samples contained
millimolar (or greater) concentrations of intermediate degradation products
(hydroperoxydienes). The company was unable to find a correlation between
the concentrations of degradation products in explants and any known use
factors.

The Advisory Group discussed this new information on 19 May 2000.

The Group considered that once the production of these degradation products
has been initiated, peroxidation will continue. The concentrations of these
degradation products will increase after sample collection in the absence
of adequate analytical controls. The lack of control on sample handling
(especially the time between explantation and analysis) complicated the
assessment of the company's results.

Although a fraction of the degradation products measured were accepted as
being post-sampling artefacts, the Advisory Group concluded that, at the
concentrations measured, such artefacts would not be sufficient to
disregard the findings of the tests.

Aldehyde degradation products.

The metabolism of fats in the body produces low concentrations of
degradation products. The degradation products are known to have a number
of biological effects. These include effects on cell proliferation .Certain
degradation products are known to be cytotoxic at micromolar
concentrations; they are also known to be very reactive towards primary
amino groups in proteins and DNA.

Genotoxic risk.

The Advisory Group agreed that:

     at the reported levels, aldehydes would react (form adducts) with
protein and DNA;
     this would result in a genotoxic hazard;
     leakage (or "bleed") through the implant shell could result in
continuous exposure to this hazard and rupture would lead to a large single
exposure;
     deficiencies in the data provided did not permit accurate estimation
of the genotoxic risk, but this risk could be significant;
     the manufacturer's previously conducted mutagenicity studies were
technically flawed both in the use of extracts and in the absence of aged
     characterised oil therefore they did not provide any reassurance
concerning the genotoxic potential of the degradation products.


The Advisory Group noted that clear evidence of a possible increased cancer
risk in women was unlikely to be available for many years.

Reproductive toxicity risk.

The Advisory Group concluded that exposure to genotoxic degradation
products resulting from diffusion of filler through the shell (bleed) or
from rupture posed a potential reproductive toxicity risk whilst the
implants were present. However due to the short half-lives of the
degradation products, the Advisory Group's opinion was that this risk was
unlikely to remain after explantation.

The Advisory Group agreed that it was prudent to advise that pregnancy
should be avoided (by use of contraception) until the implants were
removed, but that this precaution would not be necessary after explantation.

In the Advisory Group's opinion, the possibility of genotoxic degradation
products migrating from implants to breast tissue and milk could not be
discounted. It was therefore prudent to recommend that breast-feeding
should be avoided prior to explantation of Trilucent breast implants.

The Group stressed that the advice on pregnancy and breast-feeding were
precautionary. The advice was based on their inability to exclude these
risks on the data available rather than any direct evidence for such effects.

Capsule.

The Advisory Group was informed that the capsule formation around Trilucent
breast implants differed from that observed with other breast implants. The
capsule felt like lumps around the implant and the shell appeared
incorporated into the capsule. Although these differences might be due to
other causes (such
as the surface texture of the implant), it was the Advisory Group's opinion
that the possible involvement of degradation products in producing this
unusual capsule morphology could not be ignored.

Clinical issues.

It was the Advisory Group's opinion that women should be provided with as
much information as possible, including the uncertainties and areas where
no information was available. Women had the right to make an informed
choice on whether or not to undergo explantation in response to the known
facts.

The Advisory Group recognised that the majority of women would not be
content with explantation alone but would want replacement breast implants.

The Advisory Group emphasised that there were other aspects that needed to
be included in a comprehensive package of care provided to women with
Trilucent breast implants. These included: clinical monitoring of the
consequences in women (whether or not they chose to undergo explantation);
possible psychological effects both from the possible loss of the breast
and also worry about long-term consequences.

Recommendations.

The Advisory Group concluded that:

     there was an explicit risk from the potential release of genotoxic
products as a result of the on-going "bleed" and the possible rupture;
     although there were insufficient data to establish an increased risk
of cancer or reproductive toxicity, these possible risks could not be
excluded
     all women with these implants should be informed that removal of
Trilucent breast implants was recommended because of these risks.

The Advisory Group stressed that even if Trilucent breast implants were
explanted from women, additional studies would be needed to further
characterise the risks and to provide further information to these women.

The Advisory Group concluded that there was no data on the safety of
implanting other breast implants subsequent to the removal of Trilucent
breast implants and women needed to be informed that there was no
information either way on this matter.


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