SPECIAL ARTICLE * ARTICLE SPECIAL

Summary of the report on silicone-gel-filled breast implants Independent Advisory Committee on Silicone-Gel-filled Breast Implants O n Feb. 17, 1992, the Honourable Ben6it Bouchard, minister of national health and welfare, appointed the Independent Advisory Committee on Silicone-Gel-filled Implants. The committee was asked to (a) provide its views (by telephone conference on Feb. 21, 1992, and in a summary letter by Feb. 28, 1992) on the proceedings and outcome of hearings held in February 1992 by the General and Plastic Surgery Devices Panel of the US Food and Drug Administration (FDA), (b) advise the minister on the interpretation of the evidence presented at the FDA hearings with respect to health risks associated with silicone-gel-filled implants (SGFIs) in a report to be submitted by the end of April 1992 and (c) recommend further steps that the Department of National Health and Welfare (DNHW) might consider to clarify the issues associated with the use of breast implants.

Background information Overview of SGFIs SGFIs were first used in 1962 in the United States;' the first use in Canada may have been in 1969. How many women received implants in either country is uncertain; estimates vary from 1 to 2 million in the United States and, by extrapolation, from 100 000 to 200 000 in Canada. These implants have varied in size, shape and type of surface (smooth, textured or coated with polyurethane foam). Foam-covered implants were first used in

19722 but did not become popular until 1981; by the late 1980s they had generated a major controversy about the carcinogenic effects of biodegraded foam. Other materials and methods have been used for breast augmentation: paraffin (in 1900), autogenous tissue (in 1895), polyvinyl alcohol sponges, polytetrafluoroethylene, polyurethanes, injection of silicone fluid and saline-filled silicone implants.3'4

Regulatory history Although regulations for devices have been in force in Canada since 1975, breast implants were not covered until a 1982 amendment extended a premarketing requirement for evidence of safety and effectiveness to all devices manufactured after October 1982 for implantation in tissues or bodies for more than 30 days. All implants marketed before that date were exempt from the new requirements. Other events subsequently affecting the distribution of breast implants in Canada included the following. * The convening of an independent expert panel by the CMA at the request of the DNHW. The panel concluded that polyurethane-foam-covered SGFIs were associated with at most a negligible increase in cancer risk.5 A similar conclusion had been reached by the 1989-90 Committee on Carcinogenicity of the Department of Health and Social Security in Britain.6 * Voluntary withdrawal of Meme implants (polyurethane-foam-covered SGFIs) from the market by the manufacturer in April 1991.

Members: Drs. Cornelia J. Baines (chair and principal author), Department of Preventive Medicine and Biostatistics, University of Toronto, Toronto, Ont.; Jocelyne Arseneau, Department of Pathology, McGill University, Montreal, Que.; Paul Davis, Department of Medicine, University ofAlberta, Edmonton, Alta.; and Dennis C. Smith, Centre for Biomaterials, University of Toronto, Toronto, Ont.

Copies of the full report may be obtained from the Publications Distribution Centre, Department of National Health and ON KIA OK9 -

For prescribing information see page 1274

Welfare, Ottawa,

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* Declaration by the DNHW on Jan. 8, 1992, of a moratorium on the distribution of the remaining SGFIs in Canada following a similar moratorium by the FDA 2 days earlier. The information that had precipitated the US decision was not released at that time.

* Autologous implants are structured from the woman's own tissue. * Other alternatives include external breast prostheses and padded brassieres.

Demographic characteristics of implant recipients

Structure and indications The basic structure of SGFIs is a silicone elastomer envelope (shell) of varying thickness that encloses different volumes of silicone gel; the gel comprises a matrix of silicone polymers permeated by silicone oils. SGFIs are used primarily for breast augmentation (in 80% of implant recipients in North America); they are also used for reconstruction after surgery for breast cancer (in about 20%) and, in a very small proportion, for correction of congenital defects or unsuccessful breast reduction procedures. The implants can be inserted either superficial to the muscles covering the chest wall (subglandular or submammary) or deep to these muscles (submuscular or subpectoral).

Alternatives to SGFIs * Saline-filled implants have been used for at least two decades. They consist of a collapsed singlelumen silicone elastomer envelope that can be inflated with sterile saline. Critics argue that they do not feel like breasts, can deflate (with local absorption of saline) and, if inserted subglandularly, ripple with postural changes. Nevertheless, some surgeons claim that submuscular implantation achieves a good esthetic result and has fewer complications (e.g., contracture) than other implants.7 Double-lumen implants were designed to overcome the leakage problems experienced with the single-lumen implants. A silicone envelope surrounds an outer lumen filled with saline and an inner lumen filled with silicone gel (or vice versa). These implants are vulnerable to the same criticisms directed at standard SGFIs. * Polyurethane-foam-covered SGFIs are no longer manufactured or marketed in North America, although they are used in other countries. Uncomfortable capsular contraction has occurred less frequently with this type of implant than with uncoated SGFIs;8 however, they are difficult to remove when explantation is required.9 How the foam degrades in vivo and what the sequelae actually are remain under investigation. * Expandable implants are designed to stretch the skin gradually through inflation of a saline-filled silicone envelope so that the skin will be able to cover an implant. This type of implant has not yet been reviewed. 1142

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Although national statistics are unavailable for the United States and Canada, in 1990 the American Society of Plastic and Reconstructive Surgery (ASPRS) noted that of the more than 130 000 women recorded as having undergone augmentation 65% were under 35 years of age.10 In contrast, 86% of those who had undergone reconstruction were 35 or older; this finding corresponds with the incidence of breast cancer. In addition, before foam-covered SGFIs were removed from the market over 80% of augmentation procedures involved SFGIs, of which 25% were foam-covered. If a best estimate for the number of living women with silicone implants is about 1 million in the United States, an extrapolated estimate would be 100 000 in Canada. The estimates are rough because numbers of women do not represent numbers of implants. Also, it is unknown how many repeat implant procedures were performed, how many women chose explantation without replacement or how many women with implants have died.

Information arising from the FDA hearings The information prompting the FDA's January 1992 moratorium on SGFIs included the

following. * Internal memoranda from Dow Corning that indicated concern about implants manufactured in the 1970s with respect to inadequate quality-control specifications, immune reactions in rats caused by silicone components, and "bleeding" of silicone fluid through the intact silicone envelope. * Reports from surgeons of implant rupture and its consequences. * Reports of systemic disease (e.g., autoimmune disorders) in implant recipients.

Implant problems Materials: The FDA cited evidence of variable consistency and composition of the silicone gel, changes in composition over time and variation between batches. Variable thickness of the silicone envelope among older implants (manufactured before 1985) and surface defects were mentioned. Differences in composition between manufacturers were acknowledged but not described. LE 15 OCTOBRE 1992

Physical properties: The mechanical tests used by the manufacturers do not reflect the stresses and strains imposed on implants in women's bodies. A full range of mechanical and physical tests could have measured the cohesiveness of the gel, the tensile strength and ultimate elongation of the elastomer, the tear and abrasion resistance of the elastomer, flex, compressive fatigue (testing would determine the pressure at which rupture might occur) and the rate of leakage (gel "bleed"). "Bleeding" refers to the very slow diffusion of silicone components from the gel and the envelope through the intact envelope to the external surface of the implant and beyond. This phenomenon has long been recognized." Annual bleed rates of 60 to 100 mg for old implants and 5 to 10 mg for new implants were reported for Dow Corning products. Complete identification and quantification of all chemicals extractable from each of the structural components of SGFIs as they are found in the final product have yet to be reported. Manufacturing changes: Changes in materials composition and in the shape, size and texture of the implants over the last 15 years make it difficult to evaluate the functional performance and outcomes of SGFIs. Clinicians appear not to have been fully informed on such changes, and patient records often do not document specific types of implants used. Since 1980 breast implants have carried markers that identify the manufacturer. Rupture: Rupture occurs when the silicone elastomer envelope is breached and gel escapes in macroscopic quantities. The spilled silicone gel may be contained within the fibrous capsule that often surrounds an implant and can prevent further migration of the gel, and the event may not be detected by either the woman or her physician. If the fibrous capsule is fragile, incomplete or ruptured by trauma the gel can escape from the implant site through tissue planes; a change in breast shape is likely to coincide with this and thus be noticed. Surgeons offered conflicting testimony to the FDA panel. Some reported that gel spills were usually confined within an intact fibrous capsule and that problems in removing the implants were rare. Others described difficulties in removing gel that had spilled beyond the capsule, especially if the gel had lost cohesiveness. A recent survey of 160 Canadian plastic surgeons found that at the time of explantation, gel leak was confined within the fibrous capsule in over 90% of cases (Dr. Carolyn L. Kerrigan: personal communication, 1992). Rupture may be occult: it may not cause discomfort or other symptoms, and it may not be detected by the physician. Occult rupture can occur either with the fibrous capsule intact or with exOCTOBER 15, 1992

tracapsular migration of gel. Once recognized, rupture is generally accepted as an indication for removal of the implant. A number of factors may be responsible for rupture: manufacturing defects in the envelope, stresses at the time of implantation (if the implant is thrust through too small an opening in the skin the silicone envelope may weaken and subsequently rupture 6 to 12 months after implantation), and long-term and repetitive stresses of daily activity (walking, running, lying prone, being hugged and playing sports). Also, closed capsulotomy (external pressure applied to the breast to rupture a tight fibrous capsule) can rupture or weaken the silicone envelope. Long discredited,' closed capsulotomy continues to be recommended and performed (Dr. Carolyn L. Kerrigan: personal communication, 1992). 12 External trauma, compression during mammographic imaging and long-term deterioration can also cause rupture. Manufacturers claim that explanted devices have not lost strength 2 to 3 years after implantation; however, clinical problems reported 7 to 10 years after implantation suggest that long-term deterioration may occur, perhaps through poorly understood biologic degradation. A detailed Canadian study of 269 explanted breast prostheses revealed an increasing incidence of deterioration with length of time in vivo. '3 The frequency with which rupture occurs is disputed. The manufacturers testifying at the FDA hearing (Dow Corning, Mentor, McGhan and Bioplasty) all reported in-vivo rupture rates of well under 1%. A Dow Corning spokesperson noted that between 1970 and 1985 the company issued free implant replacements to encourage surgeons to report ruptures. Since 1985 it has also offered a lump sum payment of $600. Not mentioned was whether acceptance of the combined offer (free implant plus cash) required patients to waive their right to sue. How effective the incentives were in encouraging complete reporting of these adverse effects is unknown. Not surprisingly, observed rupture rates in explantation series were much higher: 31.9% in the Canadian study of 269 explants, a further 8% being ".completely destroyed."'3 However, the experience of women requiring explantation cannot be generalized to an asymptomatic population with apparently intact implants. More accurate rupture rates can only be estimatthe use of data from a representative sample with ed with implants. Such an estimate is not women all of currently available. Surgical problems: After an apparently successful implantation, reoperation (revision) may be required for the following reasons. 0 Explantation after rupture of SGFIs or deflaCAN MED ASSOC J 1992; 147 (8)

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tion of saline-filled implants. Although there was consensus at the FDA hearings that ruptured SGFIs should be removed, there was no such consensus on the management of asymptomatic rupture confined within the fibrous capsule. In the survey of Canadian plastic surgeons 129 of the 160 surgeons indicated that they would routinely remove implants if rupture were diagnosed. * Correction of capsular contraction. Not all

nation by the woman, physical and visual examination by the physician, mammography and ultrasonography. Periodic mammography screening for silicone leaks should not be used in women under 35. A decision to initiate such screening at an early age would require assurance that the benefit would outweigh the cumulative risk of any radiation exposure. 5 Furthermore, there is no generally accepted contractures are corrected. mammographic procedure for detecting leaks, but * Correction of implant size or position. two to four times the usual radiation dose is required * Control of infection immediately postopera- when silicone implants are in place. The surveyed tively or later. This complication usually requires Canadian plastic surgeons reported that diagnosis of removal of the implant and probably occurs infre- implant rupture is very difficult and that mammography results may be negative even when surgery quently. 14 Accurate estimates of the rates of and the reasons confirms the rupture. for surgical revision must be derived from representaAt the FDA hearings Harris'6 reported 21 cases tive samples of women with implants. Such estimates in which ultrasonography was used to assess the are not yet available. implant status. Although Harris felt that ultrasonogBiologic problems: Three main components of raphy was better than mammography at detecting SGFIs may be associated with a biologic response: silicone leaks, the ensuing discussion suggested that the silicone oil (fluid), the cross-linked gel-matrix the reliability of ultrasonography for this purpose material, and the silicone elastomer envelope and its has not yet been established. associated silica filler. Biologic problems include Screening for early detection of breast cancer: The development of a surrounding fibrous capsule, con- special mammographic displacement technique adtracture of the capsule causing pain, excessive firm- vocated by Eklund and associates'7 may not be used ness and distortion of shape, mineralization of the in all facilities offering mammography for women capsule, infiltration of lymph nodes with silicone with implants. As well, the interpreting radiologist material, the development of granulomas, possible may not always know whether the mammography systemic distribution and organ involvement, and has been requested to detect silicone leakage or the possible presence of silicone products in breast cancer. Without the special displacement technique milk and other body fluids. 22% to 83% of glandular tissue may be obscured by Neither the frequency nor the health impact of the SGFI.'8 Even with the technique the amount of these problems is known, and their relation to the measurable tissue was 36% less than what was associated disease states that have been observed has visualized before augmentation.'9 In women with yet to be defined. submuscular implants the decrease was only 15%. Other problems: Women with implants may It was generally agreed that guidelines for breast experience a diffuse burning sensation in their cancer screening applied to the general population breasts and altered sensation of the nipple-areola should also be applied to women with implants.

complex. For women wanting saline-filled implants, costs are likely to increase. Since January 1992 prices for saline-filled implants have risen by 50%, and further increases are planned (Business Week, New York, Apr. 6, 1992: 28). A major concern expressed at the FDA hearings was the cost of explantation when the procedure was indicated, and there were reports of escalating surgical fees. The provincial and territorial governments are currently developing policy on explantation.

Screening women with implants Screening for implant rupture: Four methods are potentially available for detecting implant rupture or risk factors for rupture (e.g., herniation of the silicone envelope through a fibrous capsule): exami1144

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Diseases associated with breast implants The suspected association between autoimmune diseases and SGFIs has arisen from over 100 case reports. However, to confirm a causal association these diseases must be shown to occur more frequently in women with implants than in women without implants. Autoimmune diseases include rheumatoid arthritis, hemolytic anemia, thrombocytopenia, scleroderma (systemic sclerosis), systemic lupus erythematosus, polymyositis-dermatomyositis, undifferentiated connective tissue disease, human adjuvant disease (the existence of which is disputed) and Sjogren's syndrome. Diagnostic criteria have not been defined for all these disorders. A confidential background document prepared LE 1 5 OCTOBRE 1992

for the FDA hearings provided details of the 120 case reports published through 1991 and used to support an association between autoimmune disease and breast implants. A number of reports revealed poor or absent case definition and failure to apply conventional diagnostic criteria. Also, the review highlighted an inconsistency in how human adjuvant disease was reported, some authors having described cases that were indistinguishable from rheumatoid arthritis, others having used the term as a label for cases not meeting the criteria for any known rheumatic or autoimmune condition. Forty-six of the 120 cases involved Japanese women who had undergone liquid injection for breast augmentation; only 2 were reported after 1969, and in only 14 was the liquid identified as silicone. In two case reports silicone bone prostheses had been used, and in neither report did the authors ever mention autoimmune disease. In the remaining cases the types of implants were not identified. Additional problems included lack of ascertainment of disease status at the time of implantation and lack of a consistent latency period between implantation and diagnosis of disease. Finally, explantation was not consistently associated with relief of symptoms. The confidential report agreed with the conclusion reached by a group in the British Department of Health and Social Security. The reported cases of so-called autoimmune disease in women with implants are far less numerous than would be expected in women without implants. The reported number, even if multiplied 10-fold to account for under-reporting of disease, would not equal the expected incidence. Since diseases occur in women without implants, it must be expected that they will occur in women with implants. Do specific diseases occur more frequently in women with implants than in those with no implants? There is insufficient evidence to answer this question reliably with respect to autoimmune diseases. Whatever evidence is available does not point to a health crisis. Criticisms about the case reports presented at the FDA hearings included vague case definitions (specific diagnostic criteria exist for some of the diseases) and selection bias. The latter alluded to the problem that facilities known to have a special interest in a particular problem attract patients with that problem and that this group may not be representive of the entire population of women with breast implants and the problems they may have. A survey by the Canadian Rheumatism Association generated 50 responses but represented the experience of more than 50 clinicians (Dr. Paul Davis: personal communication to Dr. A.J. Liston, assistant deputy minister, Health Protection Branch, DNWH, 1992). It revealed that only 59 patients had OCTOBER 15, 1992

symptoms and coexisting silicone breast implants: 34 had nonspecific arthralgias and myalgias, the features in many cases fulfilling the criteria for fibromyalgia, which is associated with no risk of death and relatively low morbidity. Fibromyalgia is prevalent in middle-aged women; therefore, it is not possible to conclude whether women with implants are at increased risk for the syndrome. Of the remaining 25 patients 4 had systemic lupus erythematosus, 3 rheumatoid arthritis, 1 Sjogren's syndrome, 1 polymyositis-dermatomyositis, 1 myasthenia gravis, 1 morphea and 1 Raynaud's phenomenon. However, 13 patients had systemic sclerosis, more than the rheumatologists expected. Two scleroderma registries were mentioned at the FDA hearings, but no information on their data was given. It has since been learned that one of the registries has reports of 725 patients with scleroderma, 7 of whom had previous silicone implants. The implant rate of 1% in this group parallels the rate of about 1% in all women. An Ottawa study20 revealed that only 1 of 47 women with systemic scleroderma had breast implants. If exposure to SGFIs causes scleroderma, a higher proportion of implant use would be expected in women with scleroderma than in the general population. Of 3500 patients with scleroderma in a US study2' 25 had breast implants - a prevalence rate of 0.7%. If 80% of the estimated 100 000 women with implants in Canada had augmentation procedures and were 20 to 50 years of age, as in the ASPRS survey,9 about 1.2% of the 6.4 million Canadian women aged 20 to 50 (1991 Canada Census data) have implants. Thus, if scleroderma patients in Canada have an implant rate similar to that among Americans with scleroderma (i.e., 0.7%), their exposure to implants appears to be less than that in the normal population. Current evidence does not point to any causal association between scleroderma and breast implants.

Conclusions At the FDA hearings some women testified that they would rather be dead than not have their SGFIs; others felt that their lives had been or were being destroyed by their implants. Still others demanded an end to the moratorium because they want to acquire these implants with no further delay. Attitudes toward breast implants are polarized, and feelings are intense. It is clear that women, after being fully informed about the existing evidence on the risks and benefits, will reach different decisions about whether to keep, remove or request implants. After experiencing and reflecting on the FDA hearings, talking to experts in diverse fields and reading extensive literature on breast implants, the CAN MEDASSOCJ 1992; 147(8)

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independent advisory committee found that there is inadequate information or an absence of reliable data on the mechanical and physical properties of SGFIs, the chemical constituents of SGFIs, the "natural history" of SGFIs (how long they continue to function acceptably), the demographic features of the population of women with implants, the prevalence and incidence of complications and specific diseases in such women, the subjective benefits of implants, the cost-effectiveness of implants and appropriate mechanisms by which implant-related problems can be identified. There is an absence of evidence establishing that women with SGFIs are more likely than those without SGFIs to have autoimmune disorders. Although reassuring, this lack of evidence neither disproves nor rules out an association. More research will be required to understand the biologic behaviour of the components of SGFIs - not only the silicone materials but also residual manufacturing components such as platinum and vinyl groups. In light of the available information it is perplexing that some Canadian surgeons believe silicone is inert, practise closed capsulotomy and do not necessarily regard rupture as an indication for explantation (Dr. Carolyn L. Kerrigan: personal communication, 1992). Canadian guidelines must be developed to clarify and define the optimal methods for implantation and management of breast implants.

Recommendations 1. Research to supplement the current knowledge about the physical and mechanical behaviour and the biologic consequences of SGFIs should be supported. 2. In response to the needs of women who currently have implants a toll-free number would be useful for answering questions from the public. In addition, workshops convened by the CMA should (a) develop guidelines for screening women for implant abnormalities, breast cancer and the need for surgical revision, (b) assess new information about risks associated with implants and (c) design continuing education programs for physicians. 3. In response to the needs of women who wish to have implants, consensus should be developed on the optimal methods for fully informing women about the risks and benefits of breast implants and on the optimal guidelines for surgical procedures and management. Also, all women receiving implants should be entefed into a registry to facilitate followup in case of prQblems. Finally, if SGFIs continue to be available and women reject saline-filled implants as an alternative, SGFIs should be made available on a compassionate basis to women requiring recon1146

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struction after surgery for breast cancer and those 40 years or more requesting augmentation. 4. Since many types of implants other than breast implants may also be associated with problems after implantation, a national implant registry should be established.

References 1. Cronin TD: Silicone breast implants. In Rubin LR (ed): Biomaterials in Reconstructive Surgery, Mosby, St. Louis, 1983: 552-563 2. Review of the Regulatory and Administrative Issues Concerning the Meme Breast Implant, Dept of National Health and Welfare, Ottawa, 1991 3. Letterman G, Schurter M: A history of augmentation mammaplasty. In Georgiade NG, Georgiade GS, Riefkohl R (eds): Aesthetic Surgery of the Breast, Saunders, Philadelphia, 1990: 41-48 4. Batich C, DePalma D: Materials used in breast implants: silicones and polyurethanes. J Long-Term Effect Med Implant 1992; 1: 255-268 5. Expert Panel on the Safety of Polyurethane-covered Breast Implants: Safety of polyurethane-covered breast implants. Can Med Assoc J 1991; 145: 1125-1128 6. Report from the 1989-90 Committee on Carcinogenicity, Dept of Health and Social Security, London 7. Biggs TM, Yarish RS: Augmentation mammaplasty: retropectoral versus retromammary implantation. Clin Plast Surg

1988; 15: 549-555 8. Handel N, Silverstein MJ, Jensen JA et al: Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis. Plast ReconstrSurg 1991; 88: 475-481 9. Bruck HG: Long-term results of polyurethane-covered prostheses. Aesthetic Plast Surg 1990; 14: 85-86 10. Statistics Update, American Society of Plastic and Reconstructive Surgery, Chicago, 1990 11. Barker DE, Retsky MI, Schultz S: Bleeding of silicone from bag-gel implants and its clinical relation to fibrous capsule reaction. PlastReconstrSurg 1978; 61: 836-841 12. Caffee HH: Breast implant capsular contracture (invited commentary). J Long-Term Effect Med Implant 1992; 1: 281 284 13. Guidoin R, Rolland C, King M et al: Morphological analysis of 269 surgically excised mammary prostheses. In Silicone in Medical Devices. Conference Proceedings, Feb 1-2, 1991 (FDA 92-4249), US Dept of Health and Human Services, Baltimore, 1992: 211-231 14. Kerrigan CL: Report on the Meme Breast Implant, prepared for the Dept of National Health and Welfare, Ottawa, 1989 15. Johnson GC: Breast Imaging and Silicone Gel Implants, FDA General and Plastic Surgery Devices Panel transcript, Feb 1992; 1:116-126 16. Harris KM: Detection of silicone implant leaks: a new sonographic sign. Idem: 105-116 17. Eklund GW, Busby RC, Miller SH et al: Improved imaging of augmented breast. Am J Roentgenol 1988; 151: 469-473 18. Hayes HJ, Vandergrift J, Diner WC: Mammography and breast implants. Plast Reconstr Surg 1988; 82: 1-8 19. Silverstein MJ, Handel N, Gamagami P: Mammographic measurements before and after augmentation mammoplasty. Plast Reconstr Surg 1990; 86: 1126-1130 20. McKendry RJR, Cyr M, Dale P: Benign breast disease in systemic sclerosis: a case-control study. Clin Exp Rheumatol 1992; 10: 235-239 21. Autoimmune Symptoms in Breast Implant Patients: Clinical Experience, FDA General and Plastic Surgery Devices Panel transcript, Feb 1992; 1: 245-276 LE 15 OCTOBRE 1992

Summary of the report on silicone-gel-filled breast implants. Independent Advisory Committee on Silicone-Gel-filled Breast Implants.

SPECIAL ARTICLE * ARTICLE SPECIAL Summary of the report on silicone-gel-filled breast implants Independent Advisory Committee on Silicone-Gel-filled...
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