1
REPORT REGARDING ASPECTS OF DIAGNOSTIC IMAGING
AFTER MACROLANE INJECTION IN THE BREAST
This report is written on behalf of the Medical Products Agency (MPA), as an attempt to
answer questions regarding the significance for the results of mammography, of a Macrolane
injection in the breast. It addresses imaging experiences in breast radiology in women treated
with Macrolane, in particular within mammography screening, and contains a review of the
published scientific literature.
Table of Contents
Page 2 Summary
Page 3 Background/information on screening with mammography
Page 4 Radiological imaging of breast implants
Page 5 Compilation of Macrolane examinations at Danderyd Hospital and Karolinska
University Hospital
Page 6 Image interpretation after Macrolane injection
Page 7 Literature Review
Page 10 References
The report is written by
Edward Azavedo
Associate Professor, Senior Consultant, Mammography Section, Department of Radiology,
Karolinska University Hospital
Helene Grundström
Senior Consultant, Mammography Section, Department of Radiology, Danderyd Hospital
2
SUMMARY OF THE REPORT ON MACROLANE IN BREASTS
Women with breast implants taking part in the mammography screening program in
Stockholm comprise roughly about 2% of all women that participate in the program.
The number of women with Macrolane injected in their breasts is currently very small in the
group taking part in the mammography screening in Stockholm, about 0.02%.
95% of these women with Macrolane injections will receive separate, specialized response
letters, written differently depending upon the interference of Macrolane in their breast tissue.
The scientific documentation about Macrolane in breasts is limited, particularly regarding
effects on breast imaging. The available documentation of the effect on breast imaging
supports conclusions from our own experience in mammography departments at Danderyd
Hospital and Karolinska University Hospital in Stockholm.
- Macrolane in breasts interferes significantly with the assessment of the breast tissue.
- Macrolane can remain in the breast tissue for a long time.
-Lumps may occur due to Macrolane and lead to unnecessary further investigation. There is
also a concern that these lumps may mask a possible development of a cancerous lump, as
reported in one of the references (6).
-Ultrasound can improve the assessment of breast tissue to some extent. However, the image
may be difficult to interpret also with ultrasound. Furthermore it requires involvement of a
radiologist which is a matter of resources in terms of time, availability and costs.
-MRI is likely to be better but is time-consuming and costly and its availability is very
limited.
3
BACKGROUND/INFORMATION ON SCREENING WITH MAMMOGRAPHY
According to the recommendations of the Swedish National Board of Health and Welfare, all
women aged 40-74 are to be offered mammography screening on a regular basis. Due to a
lack of resources, just over half of the county councils are estimated to have started with
women aged 50-69. The age range for screening invitations has been gradually widened, in
both directions. Participation in screening varies across the country. The levels are lower in
the major cities. In Stockholm, the level of participation is around 70-75%.
All county councils implement a computerized administration of the whole screening
programme, which means that within each county council, there are uniformly worded
standard letters for both the screening invitation and the examination results.
In this report we have chosen to use figures from Stockholm where majority of the cases exist.
To account for the whole country’s statistics with regards to certain issues, demands a great
deal of time and effort.
In Stockholm, mammography screening was started in 1989, and all women aged 50-69 are
regularly offered a mammography. In recent years, the 40-50 age group has been included
and, from January 2012, the 70-74 age group as well.
Figures in the table show the number of women who had a mammography at Danderyd
Hospital and Karolinska University Hospital respectively, as well as within the whole of
Stockholm County Council during 2010.
Total
KH + DH
All of Stockholm
28730
53318
145.112
5157
13024
67.541
Karolinska
University Hospital
KH
Danderyds Hospital
DH
40 – 69
years of age
24588
40 – 49
years of age
7867
In conjunction with the age groups in Stockholm having been widened to include younger
women, we seem to have seen an increasing number of women with breast implants. A rough
estimate of the current number of women with breast implants participating in the screening
in Stockholm is 2%. At Karolinska University Hospital and Danderyd Hospital, this amounts
to a total of just over 1,000 women per year.
Only a few, approximately 0.02% of all women screened each year at Karolinska University
Hospital and Danderyd Hospital, have stated that they have been treated with Macrolane.
Over the past 2-3 years, 17 women who have had Macrolane treatment have been examined
with mammography at Karolinska University Hospital, and 20 at Danderyd Hospital, 16 of
which were part of the screening. Theoretically, there could be women who have been treated
with Macrolane, whose mammography image has not been affected, and who have not stated
that they have received such treatment. However, all women who were visually assessed as
having received Macrolane injections, had already stated this, in connection with the
4
examination. This suggests that the information regarding the number of women in our
mammography wards, who have been treated with Macrolane, is reasonably accurate.
Telephone contacts with colleagues around the country have shown that some of them have
had a handful of women treated with Macrolane, and some have had none at all. It is deemed
practically impossible to ascertain how many women with Macrolane - within and outside the
age ranges of the screening programme - have been examined with mammography and/or
ultrasound at private clinics.
RADIOLOGICAL IMAGING OF BREAST IMPLANTS
Women who have silicone implants, or implants of a similar type, can be examined with
mammography. Through the nurse manipulating the submuscular implant, the breast tissue
can be compressed when the image is captured. The image can subsequently be radiologically
assessed. These women can receive regular standard responses to their mammography
examinations.
For women who have had Macrolane injections, the breasts can be compressed and x-rayed as
usual but the examinations are, as a rule, more difficult to assess. Macrolane, which is radioopaque, has masked the breast tissue, which makes it difficult, or impossible, to assess the
breast tissue.
Neither Karolinska University Hospital’s nor Danderyd Hospital’s mammography Sections
have received referrals for mammographies for women prior to Macrolane treatment, nor
other cosmetic measures such as implant insertion or lifts. We only see referrals prior to
cosmetic operations/measures for women who are having a breast reduction or a
reconstructive surgery at the hospital after a cancer operation.
Mammography is used as a screening method for breast cancer. Mammography is the only
screening method that has scientific support for reducing mortality from breast cancer in
major populations. Complementary methods of breast imaging such as Ultrasound, Magnetic
Resonance (MRI) and Tomographic Scanning are used when required in the examination of
women with clinical symptoms, or women who are recalled after a screening examination,
due to suspected cancer. However, these methods are not included in the screening procedure.
They require increased medical resources and access to, for example, MRI, which is currently
both expensive and limited in Sweden.
Women in Stockholm who have been treated with Macrolane have, after examination, in
addition to the standard responses 1 and 2, see below, received response letters 3 or 4,
dependent on the possibility of assessment.
An example of a standard response:
1.When an examination is assessed as 'healthy': ”Your screening mammography indicated no
signs of cancer”
2. Recall letter for investigation of a lump discovered by the patient and/or as a result of a
radiological discovery.
Individual responses (‘Macrolane letters’)
3.”Your screening mammography, showed no signs of cancer within the areas of your breasts
where assessment was possible. The assessment was made more difficult due to the
Macrolane treatment you informed us about”.
5
4 “Your screening mammography can not be assessed, due to the Macrolane treatment you
informed us about.”
SUMMARY OF MACROLANE EXAMINATIONS AT DANDERYD HOSPITAL (DH)
AND KAROLINSKA UNIVERSITY HOSPITAL (KUH)
At DH over the past 2-3 years,
20 Macrolane examinations, 16 within the screening program and 4 referred patients.
Ten out of these received responses according to no. 3 above. More than 50% of the breast
tissue could be assessed but the assessment was obstructed, i.e. not entirely reliable.
Nine women received responses according to no. 4 above. They could not be assessed – less
than 50% of the breast tissue could be seen.
One woman received a normal standard letter nr 1, “no sign of cancer”.
Five women had felt lumps, which led to further examination. In four cases, the lumps were
caused by Macrolane. Three of these had participated in the screening and one was referred
due to the discovery of a lump.
One referred woman had both a benign tumour (fibroadenoma) and a local inflammatory
reaction around parts of the Macrolane.
At KH over the past 2-3 years,
17 Macrolane examinations, all as screening exams.
Eight out of these received response no. 3 above. They had more than 50% of their breast
tissue assessed, but the assessment was obstructed, i.e. not entirely reliable.
Eight women received response no. 4 above. They could not be assessed – less than 50% of
the breast tissue could be seen.
One woman received a normal standard letter. She stated that her Macrolane had been
surgically removed as lumps.
Table of Macrolane examinations at DH and KH
Total
DH
20
KH
Total
17
37
Standard
response
‘Normal’
1
1
2
Response
“Obstructed
assessment”
Response
“Could not
be assessed”
10
9
Supplementary
ultrasound,
due to
Macrolane
10
8
18
8
17
0
10
6
IMAGE INTERPRETATION AFTER MACROLANE INJECTION
The majority of the reports regarding the use of Macrolane refer to effects of plastic surgery
and viewpoints thereof. Very little has been documented about the effects of Macrolane on the
outcome of various methods of radiological breast examination. Our experience of the 37
reported examinations we have seen, is in accordance with the work of Pienaar et al:
Macrolane considerably interfered with the assessment , in 35/37 (95%) of our cases. In 17/37
of these cases (46%), the images were disturbed to such a degree that we were unable to make
any assessment at all.
10 of the mammography examinations of women with Macrolane at Danderyd Hospital were
supplemented with ultrasound due to clinical symptoms or, initially, due to the breast
radiologists’ lack of experience regarding the effects of Macrolane on the mammography
image. The advantage of ultrasound in these cases, as with normal breast diagnostics, is that
the examination is dynamic and, consequently, 3-dimensional. Despite this fact, 2 of the 10
ultrasound examinations were considered impossible to assess. Out of the others, we have
described 3 as ”very difficult to assess”, 4 as “difficult to assess” and 1 as “somewhat difficult
to assess”. No other scientific grading has been carried out
In two cases, Macrolane was seen underneath the pectoral muscle. Macrolane had also
dissected itself into the muscle and, in one case, up into the armpit. The latter considerably
obstructed assessment of the axillary tissue. In conclusion Macrolane to a large extent
disturbed the ultrasound interpretation in our 10 cases.
Our limited experience so far at Danderyd Hospital is unsatisfactory regarding the ability to
reliably assess all breast tissue using ultrasound on a Macrolane-injected breast.
It also requires involvement of a radiologist which is a matter of resources regarding time,
availability and costs.
7
REVIEW OF LITERATURE – MACROLANE
A literature search was carried out in PubMed using the search word Macrolane. A total of 13
references were found at our latest search on 14-12-2011. We have studied the reported image
diagnostic aspects following injections of Macrolane into women’s breasts, especially image
diagnostics with mammography, which is the most commonly used method and the only one
that has scientific support for use in screening for breast cancer in major populations.
One reference (12) refers to image diagnostic effects on mammography, ultrasound and MRI.
One reference shows that the amount of Macrolane injected decreases over time. Four
references are discussion items, which have been inserted; two deal with descriptions of the
location and quantity of Macrolane in the injected breast with the help of MRT; two are
literature reviews; one is a case description; two have no image diagnostic information and
one is a very short reference to mammography with no useable information.
The following is a brief summary of the articles to which we refer.
Refs 1 +2 : Inserted discussion items and not scientific studies, not included in this review.
Ref 3 : An article in French which has nothing to do with breast image diagnostics, not
included in this review.
Ref 4 : This article mentions that, with MRI, it could be noted that ‘gel’ lay subglandularly.
No further image diagnostic information is provided in this article.
Ref 5 : An article in French, which we did not translate for this review. The article’s abstract
(in English) has been reviewed, after which we came to the conclusion that it is a literature
review and not a study in its own right.
Ref 6 : A case description. A woman experienced ’skin tethering’ in one breast which was not
clinically investigated, prior to the Macrolane injections. The symptoms improved initially but
then became somewhat worse. Four months later, a malignancy was observed, which could be
both manipulated through palpation and seen using image diagnostic methods, mammography
8
+ ultrasound + MRI. Macrolane in the breast meant that a planned primary breast
reconstruction could not be offered, and it was therefore performed at a later date.
Ref 7 : A discussion article (comment on Ref 9) which deals with the use of MRI for
establishing the quantity of ‘gel’ remaining, and the ‘gel’ lying in the ‘right place’ and not in
the breast tissue.
Ref 8 : A short insertion referring to Ref 10, no actual scientific study, not included in this
review.
Ref 9 : This article states that MRI examinations were carried out 1-5 days after the
Macrolane injections, and that 3, 6 and 12 months later, ‘gel’ could be seen using MRI in
quantities equating to 78%, 57% and 34% respectively. No further image diagnostic
information is obtainable.
Ref 10 : This is a review article, which refers to a couple of Swedish studies; one of which
was a pilot study from a manufacturer which was unpublished at the time, the other is an
address given at a congress in Paris. It refers to the results quoted in Ref 9. No further image
diagnostic information is obtainable.
Ref 11 : This reference mentions that Macrolane (gel) could be seen on the mammography
image 12 months after the Macrolane injection. The ’gel’ is described as lying deep inside,
near the pectoral muscle but at the same time it is stated, in all cases, that ‘the gel was
partially superimposed over the glandular tissue’. No further image diagnostic information is
provided in this article.
Ref 12 : In this article, which the authors describe as a ’pictorial review’, there are several
pieces of image diagnostic information.
Mammography: Macrolane could be seen in well-defined concentrations in 14 cases (14/19),
5 of which (5/19) engaged the pectoral muscle. The report states that Macrolane led to a lower
sensitivity (the ability to discover a cancer) and caused false positive discoveries (false cancer
alarms).
9
Ultrasound: This technology is assessed as being better suited for differentiating Macrolane
from pathological changes. The ’gel’ was seen as hypoechoic changes (i.e., cystic changes)
but also internal echoes were seen. The occurrence of internal echoes and communicating
channels made assessment easier as it did not involve single cysts. However, in time, changes
which appeared solid were also seen in 4 cases (4/19), which led to an intervention by core
biopsy, i.e., a tissue test for microscopic analysis. In the biopsies, Macrolane and/or a fibrous
reaction could be observed. No malignancy-suspicious changes were identified in the samples
MRI: This technique was used sparingly, when other methods were insufficient. With contrast
MRI (the usual examination technique), certain contrast enhancement was seen in several
difficult to interpret cases.
Finally, it was established that, (1) since Macrolane could still be seen 24 months after
treatment, care should be implemented, especially in screening situations; (2) Macrolane
obstructs and complicates mammography image diagnostics, to varying degrees.
Ref 13 : This study encompasses 194 women who received Macrolane treatment but
unfortunately there is no information regarding image diagnostics after the treatment (not
included in this review).
Discussion: macrolane for breast enhancement: 12-month follow-up. Hedén P: Plast Reconstr
Surg. 2011 Dec;128(6):780e-1e. No abstract available
10
REFERENCES
1. Macrolane is no longer allowed in aesthetic breast augmentation in France. Will this decision
extend to the rest of the world? Chaput B, Chavoin JP, Crouzet C, Grolleau JL, Garrido I. J
Plast Reconstr Aesthet Surg. 2011 Oct 19. [Epub ahead of print] No abstract available.
2. [Macrolane(®): A severe case of calf cellulitis after modeling injection.] Chaput B, Eburdery
H, Crouzet C, Grolleau JL, Chavoin JP, Garrido I. Ann Chir Plast Esthet. 2011 Sep 5. [Epub
ahead of print] French.
3. Breast augmentation after Macrolane filler injections. Goisis M, Yoshimura K, Heden P.
Aesthetic Plast Surg. 2011 Aug;35(4):684-6.
4. [Macrolane(®), a too premature indication in breast augmentation. Focusing on current
knowledge of the product]. Chaput B, De bonnecaze G, Tristant H, Garrido I, Grolleau JL,
Chavoin JP. Ann Chir Plast Esthet. 2011 Jun;56(3):171-9. Epub 2011 Jun 2. Review. French.
5. Macrolane injections for breast enhancement in undiagnosed breast malignancy: A case
report. Crawford R, Shrotria S. J Plast Reconstr Aesthet Surg. 2011 Dec;64(12):1682-3. Epub
2011 May 24.
6. Discussion. Macrolane for breast enhancement: 12-month follow-up. Nahabedian MY. Plast
Reconstr Surg. 2011 Feb;127(2):861-2.
7. Macrolane: a safe alternative for breast augmentation? van der Lei B J Plast Reconstr
Aesthet Surg. 2011 Jun;64(6):729-30. Epub 2010 Oct 23.
8. Macrolane for breast enhancement: 12-month follow-up. Hedén P, Olenius M, Tengvar M.
Plast Reconstr Surg. 2011 Feb;127(2):850-60.
9.
Is breast augmentation using hyaluronic acid safe? McCleave MJ. Aesthetic Plast Surg. 2010
Feb;34(1):65-8; discussion 69-70. Epub 2009 Dec 5. Review.
11
10. Body shaping and volume restoration: the role of hyaluronic acid. Hedén P, Sellman G, von
Wachenfeldt M, Olenius M, Fagrell D. Aesthetic Plast Surg. 2009 May;33(3):274-82. Epub
2009 Mar 12. Review.
11. The imaging features of MACROLANE™ in breast augmentation. Pienaar WE, McWilliams
S, Wilding LJ, Perera IT. Clin Radiol. 2011 Oct;66(10):977-83. Epub 2011 May 5.
12. Early clinical experience of hyaluronic acid gel for breast enhancement. Inglefield C. J Plast
Reconstr Aesthet Surg. 2011 Jun;64(6):722-9. Epub 2010 Oct 15.
Stockholm, 6 March 2012
Helene Grundström
Senior Consultant
Mammography Section
Department of Radiology
Danderyd Hospital
Edward Azavedo
Associate Professor
Senior Consultant
Mammography Section
Department of Radiology
Karolinska University Hospital