From cadavers to implants: silicon tissue assays of medical devices

A plethora of data has been used to condemn and defend the role of silicone and its association with "adjuvant disease." In the ongoing attempt to enhance our knowledge, we have chosen to identify tissue silicon levels in patients with saline implants or tissue expanders. We have compared these levels with tissue samples from a variety of patients with and without medicinal silicone devices from both the northeast and southwest United States over a 4-year period. All specimens were harvested by a "no touch" technique, non-formalin fixed, frozen, and shipped to an independent toxicology laboratory for analysis. Inductively coupled plasma atomic emission spectroscopy was used to obtain the tissue silicon measurements. Silicon tissue values in cadaveric tissue (n = 20 cadavers; n = 120 specimens) averaged 2.2 mcg/gm of tissue with undetectable silicon levels in over 50 percent of the specimens (range 0 to 45 mcg/gm; median = 0). Silicon levels surrounding port-a-catheter devices (n = 15 patients; n = 15 specimens) averaged 8.04 mcg/gm of tissue (range 0 to 41 mcg/gm; median = 0). Tissue levels in the capsules surrounding saline (n = 10 patients; n = 22 specimens) and silicone implants (n = 31 patients; n = 58 specimens) averaged 292 mcg/gm (range 0 to 1380 mcg/gm; median = 110) and 1439 mcg/gm (range 0 to 9800 mcg/gm, median = 490), respectively. Tissue levels, however, from distant sites (n = 22 specimens) in these same patients were equivalent to the cadaveric nonaugmented values (average = 3.2 mcg/gm; range 0 to 5.8 mcg/gm; median = 2.7). The results imply that there is a continuum of exposure to silicone medical devices based on the mechanical properties of silicone. The data seem to suggest that there may be a progression of measurable tissue silicon levels based on the amount of environmental or device-related silicone exposure a person has over his or her lifetime. It is our hope that these levels will serve as a baseline for our continuing knowledge of implantable medical devices.     

Silicone breast implants: immunotoxic and epidemiologic issues

Silicone gel implants for breast augmentation and reconstruction have been in use since 1962. Significant local complications include capsular contracture, rupture, gel "bleed", and spread of the implant material to regional lymph nodes (1-7) as well as histologic findings of foreign body granulomas in the capsular tissue and in lymph nodes (7-9). Through magnetic resonance spectroscopy and atomic emission spectroscopy, silicon compounds were found in the blood of some women with silicone breast implants; silicone and silica have also been found in liver (10). Well-publicized case reports have raised significant concerns regarding an association between implants and systemic disease. However, despite the availability of silicone implants for over 30 years, controlled epidemiological studies were not carried out until 1992. Currently available epidemiologic data are extremely limited. In part, because the majority of implants were used after 1981, the incidence of long-term problems is not yet known. In 1992, due to the unavailability of studies demonstrating the safety of implants, the U.S. Food and Drug Administration advised that silicone breast implants should be used only in reconstructive surgery and as part of clinical trials (11). This decision spurred a wave of research on the bioreactivity of silicone and clinical observations of patients with implants. Herein, we review the adverse immune effects following contact with silicone as well as the epidemiologic data available.     

Silicone breast prosthesis and rheumatoid arthritis: a new systemic disease: siliconosis. A case report and a critical review of the literature

Today the number of women receiving breast implants of silicone gel, for augmentation or reconstruction of the breast, is increasing. Silicon implants may cause local complications (such as capsular contracture, rupture, closed capsulotomy, gel "bleed", nodular foreign body granulomas in the capsular tissue and lymph nodes) or general symptoms. An adverse immune reaction with signs and symptoms of rheumatoid disorders is also possible, although an increased frequency of true autoimmune systemic connective tissue diseases is controversial. The US Food and Drug Administration advised that these silicone implants should be used only in reconstructive surgery and as part of clinical trials. Silicone is not an inert substance and silicone compounds were found in the blood and liver of women with silicone breast implants. The development of disease related to silicone implants would depend on genetic factors, so that only a very few women are potentially at risk. HLA-DR53 may be a marker of predisposed subjects. Breast-feeding by women with silicone implants should not be recommended for possible autoimmune disorders in the children. We report the case of an adult female patient with silicone breast implantation for bilateral mastectomy (performed 12 months before) and a unique syndrome characterized by low-grade fever, chronic fatigue, arthralgias of the hands, dysphagia, dry eye, increased level of rheumatoid factor and decreased value of complement C3 and C4. No increased erythrocyte sedimentation rate occurred, and no ANA, nDNA, ENA and AAT autoantibodies were evidence. A critical review of literature (source: MEDLINE 1980-1997) was performed and our case seems to be the first one reported in Italy. The internist should become familiar with the immunological disorders related to silicone breast implants, often so marked to require the explantation of the prostheses to improve symptomatology. However, perhaps due to the leak and spreading of silicone, the progression to a severe systemic involvement may remain despite the implant removal.     

Breast prostheses and their complications

In the past few years silicone breast implants have been a highly charged and controversial topic for psychologic, health and politico-legal reasons for patients and for surgical, medical and research concern for professionals. Both sides are interested in knowing about the complications encountered with these implants on one hand and to find the ideal device needed for mammary reconstruction on the other. Indeed silicone does not fulfill the characteristics initially expected for a synthetic soft-tissue substitute. The local cellular response leads to the formation of a capsule around the implant with frequently unsatisfying cosmetic results. The well described leakage occurring through the silicone envelope allows the silicone gel to diffuse to multiple anatomic areas in the body. Scientific works demonstrated that silicone gel acts as a potent immunologic adjuvant and can induce antibodies to silicone surface-associated antigens. Breast implanted women who present with systemic clinical symptoms can be included either in the group of well defined connective tissue diseases or in the atypical connective tissue disease-like syndrome. The largest epidemiologic studies have shown reassuring evidence against large hazards but have documented a low but statistically significant risk of connective-tissue diseases in women with silicone gel filled implants. Practitioners must manage these patients with the awareness that reliable objective tests to identify the useful problem are not yet available.     

Silicone breast implant litigation (Part 1)

Silicone breast implant litigation has escalated in the past couple of years with the Food and Drug Administration (FDA) investigation of silicone gel implants which resulted in finally removing the silicone gel implants from the market. Plaintiffs have linked various medical problems to the presence of silicone in the body. The FDA has stated that there is no medical evidence that silicone causes autoimmune disease. Silicone has never been shown to cause breast cancer. Breast implants can result in complications such as capsule contracture, gel bleed, implant rupture, calcifications around the implants, and possibly interference with mammography in the diagnosis of breast cancer. Plaintiffs have claimed that the implant manufacturers knew of the defects in the silicone shell implant covering, and covered up the facts. The product liability action has become a class action, and a proposed settlement has been made in terms of which implant recipients with any problems will be reimbursed. Furthermore, there will be coverage for future implant problems over the next 30 years. There will still be some litigation by those patients who have opted out of the settlement agreement.     

Rupture of silicone-gel breast implants: causes, sequelae, and diagnosis

Silicone-gel-filled breast implants have been widely used for breast augmentation and reconstruction after mastectomy. The rate of implant rupture and its sequelae are not known. We review the frequency, causes, sequelae, and detection of implant rupture. Materials testing of removed implants provides evidence that as implants age in vivo, they weaken and may rupture. Sequelae of rupture include migration of gel accompanied by inflammation and silicone granuloma formation. The role of free silicone gel in relation to idiopathic or atypical connective tissue disease is not clear. Magnetic resonance imaging is substantially more sensitive in the detection of rupture than is mammography or ultrasonography.     

Silicone breast implants and connective tissue disease: an overview

Silicone breast implants have been implicated in the possible pathogenesis of various connective tissue diseases. These findings have had a major impact not only on the medical and legal communities, but also on the community at large. In this communication, we review the history of the breast implant controversy, and examine the medical evidence regarding the possible link of silicone gel implants with connective tissue disorders such as scleroderma, rheumatoid arthritis, and lupus. Finally, we give a broad overview of the topic and offer some general suggestions regarding the care of patients who have silicone breast implants.     

Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis

Silicone lymphadenopathy has been associated with fracture and/or erosive breakdown of silastic implants in joint replacements and is also known to occur with cosmetic and reconstructive breast implant surgery. In the orthopedic literature rare malignant lymphomas have been reported in association with silicone granulomas in lymph nodes; whether silicone is a causative agent remains controversial. We report a single case of a 56-year-old woman who had painful capsular contractures and a 2-cm palpable nodule medial to her silicone mammary implant. Histologically the mass comprised an extra nodal follicular mixed lymphoma with surrounding granulomatous response to polarizable foreign body material. Paraffin immunophenotyping, bcl-2 protein staining, and gene rearrangement analysis verified this diagnosis.     

Distribution of organosilicon polymers in augmentation mammaplasties at autopsy

Silicone-containing breast implants have been used since 1963 for cosmetic augmentation and breast reconstruction. Currently, there is intense debate regarding the extent and mechanism of migration of silicone from the area of implant. The current study compares tissue distribution of organosilicon polymers between women with and without silicone breast implants to determine the extent of silicone migration from breast implants. Samples were collected at autopsy from 15 individuals with bilateral breast implants with no known history of chest trauma and from 14 age- and sex-matched controls. Capsule, breast, axillary lymph nodes, abdominal fat, liver, lung, and spleen were collected for analysis of organosilicon polymers by atomic absorption spectrometry and for examination by light microscopy. Blood was collected for analysis of rheumatoid factor and antinuclear antibodies. Silicone was observed microscopically in at least one capsule section from all implant cases and in at least one lymph node in 8 of 15 implant cases. Silicone was not observed in lymph nodes from control cases. Organosilicon polymers were extracted from tissue using heptane, and the silicon content of the extract was quantitated by atomic absorption spectrometry. Silicon was detected in all capsules; statistically significant increases of organosilicon polymers were measured in axillary lymph nodes, breast, and abdominal fat from individuals with silicone breast implants when compared with the nonimplant group. Measurable amounts of organosilicon polymers were found in tissues from the nonimplant group. Suitable blood specimens were analyzed for the presence of rheumatoid factor and antinuclear antibodies. All nine implant cases tested were negative for the presence of antinuclear antibodies. Three implant cases which were tested for rheumatoid factor also were negative. We conclude that organosilicon polymers routinely migrate from the site of breast implantation to regional tissues near the implant site. Tissues from nonimplant cases often contained measurable amounts of organosilicon polymers, and tissue distribution was variable within any single individual: this is consistent with the wide-spread use and form of organosilicon polymers.     

Diagnosing breast implant rupture with MR imaging, US, and mammography

A total of 135 symptomatic women with 262 breast implants were examined with magnetic resonance (MR) imaging performed with a body coil, ultrasound (US), or both to determine imaging features of implant rupture. Surgical proof was available for 33 women with 62 implants; 24 were ruptured and 38 were intact. Complicated internal structure was the most reliable predictor of implant rupture: Diffuse low-level echoes were seen on sonograms in 56% of ruptured implants; internal membranes (which correspond to the collapsed implant shell) were seen on MR images in 58% of ruptured implants. Fluid droplets were seen within the silicone in 26% of ruptured implants on MR images. Irregular implant contour can be a sign of rupture but is unreliable. Fluid collections around silicone implants are not a sign of rupture. At present, neither US nor conventional MR imaging with a body coil is sufficiently reliable to advocate routine screening of asymptomatic women with breast implants. Evaluation with MR imaging performed with a surface coil is more reliable.     

The influence of time on human breast capsule histology: smooth and textured silicone-surfaced implants

Although the histology of capsular tissue is well described in the literature, most studies in humans do not correlate histologic findings with implant age (number of years an implant was in place before sampling). As such, questions regarding the long-term histology in humans remain. The microanatomy of 93 human periprosthetic capsular tissues surrounding 22 textured and 71 smooth silicone-surfaced prostheses was studied. The implants were divided into two groups according to the time between implantation and capsulectomy: between 0 and 5 years or more than 5 years. Hematoxylin and eosin and Masson trichrome-stained sections were analyzed by light microscopy, with and without polarization. Eighteen of the textured implants contained silicone gel and four contained saline. Sixty of the smooth implants contained silicone gel, eight contained saline, and in three, the filler type was not known. For the majority of patients, surgery was performed for augmentation mammaplasty, and the implants were removed because of capsular contracture. The following histologic features were assessed: synovial-like metaplasia, villous hyperplasia, density of the collagenous capsule, alignment of collagen fibers within the capsule, and the presence of foreign material and of a foreign body reaction. The following trends were observed. In smooth implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia (p = 0.003) and villous hyperplasia; there was no significant difference in the presence of a dense collagenous capsule, the orientation of collagen fibers, or the presence of a foreign body reaction. An increase was observed in the presence of foreign material (p = 0.01). In textured implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia, villous hyperplasia (p = 0.003), dense collagenous architecture, and parallel orientation of collagen fibers (p = 0.017). An increase in the presence of a foreign body type reaction and foreign material (p = 0.024) was observed. In comparing textured and smooth-surfaced implants, synovial-like metaplasia was observed more often in the textured group, both at 0 to 5 years (p = 0.01) and at greater than 5 years (p < 0.01). Textured implants more often had villous hyperplasia at 0 to 5 years (p = 0.03) but not beyond 5 years. Smooth implants more often had a dense collagenous capsule than textured implants after 5 years. No significant difference was seen in the orientation of collagen fibers in capsules around smooth and textured implants at 0 to 5 years. After 5 years, the incidence of capsules with collagen fibers arranged parallel to the implant surface was significantly greater in the smooth group than in the textured group (p = 0.01). The presence of a foreign body type reaction was seen more often in the textured group between 0 and 5 years (p = 0.01) and at greater than 5 years (p < 0.01), and the presence of foreign material was more often seen in the textured group between 0 and 5 years (p = 0.06) and at greater than 5 years (p < 0.01). In summary, the cytologic changes around implants seem to be dynamic in nature, and implantation duration and shell type play a significant role. Synovial-like metaplasia, villous hyperplasia, and foreign material were more often observed in the textured group within the 0 to 5 year interval. Beyond 5 years, synovial-like metaplasia, a foreign body type reaction, and foreign material were more often observed in the textured group. Differences in the density of collagenous capsules were not significant at any time point, and collagen fibers oriented parallel to the implant surface were more often observed in the smooth group after 5 years. The significance of these findings awaits further investigation.     

A note on the possibility of explaining why a color cannot be both red and green

OBJECTIVE: This study was a blinded, concurrent assessment of a historical cohort derived from a provincial registry (1978 to 1986) of breast implant recipients (cosmetic, not reconstructive) and controls (other cosmetic surgery) to test the hypothesis that connective tissue disease (CTD) is increased in breast implant recipients. METHODS: Women who underwent breast implant or other cosmetic surgery during the interval from 1978 to 1986 were contacted confidentially by Alberta Health and asked to participate in the study. Those willing to participate completed an extensive questionnaire and supplied a blood sample, subsequent to which all surgical records were reviewed to confirm implant type(s) or cosmetic surgery(ies). All participants with any suggestion of rheumatic disease were assessed blindly by a rheumatologist for CTD. RESULTS: One thousand five hundred seventy-six breast implant recipients were recruited, including 1112 who had received silicone gel-filled implants (> 13,500 person yrs exposure). Seven hundred twenty-six controls were recruited. Prevalence rates adjusted for sex and age for rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and Sj?gren's syndrome (the principal targeted conditions) were consistent with published reports for Caucasian women. While breast implant recipients self-reported significantly greater rates of symptoms than controls, post-surgical diagnoses of the principal targeted conditions did not indicate an increased incidence of typical or atypical CTD. CONCLUSION: The results of the study do not support the hypothesis that silicone gel-filled implants induce or promote CTD.     

Changes in photon dose distributions due to breast prostheses

PURPOSE: Subcutaneous prosthetic implants had been routinely used for cosmetic augmentation and for tissue replacement following mastectomy over the last 15 years. The implants come in many forms as the gel filler material and surrounding shell material(s) vary significantly. METHODS AND MATERIALS: This study uses a thin window parallel-plate chamber and thermoluminescent dosimeters to quantify and dosimetric changes to surrounding breast tissue due to the presence of the prosthesis. A mammographic phantom was compared to four commercial prostheses, namely two silicon gel fillers within two different shells (silicon or silicon/polyurethane), a tri-glyceride within silicon and a bio-oncotic gel within silicon/polyurethane. The latter two implants were designed with a low-Z fill for diagnostic imaging benefits. RESULTS: Ion chamber results indicate no significant alteration of depth doses away from the implant with only minor canceling (parallel opposed) interface perturbations for all implants. In addition the physical changes to the irradiated prostheses were quantified by tonometry testing and qualified by color change. Each implant exhibited color change following 50 Gy, and the bio-oncotic gel became significantly less formable following irradiation, and even less formable 6 weeks postirradiation. CONCLUSION: The data indicates that prostheses do not affect the photon beam distribution, but radiation does affect the prostheses.     

Controversy over the silicone gel breast implant: current status and clinical implications

The silicone gel breast implant controversy has generated much confusion, making informed decision making for physicians and patients increasingly difficult. In order to better understand the controversy, we review the steps taken by the Food and Drug Administration and the resultant status of breast implants. The currently available scientific data are summarized with regard to cancer development and detection, implant rupture and gel migration, and autoimmune disorders. By reviewing the presently available information on silicone gel breast implants, we can better address the concerns of our patients.     

Strength of silicone breast implants

Rupture and leakage are recognized problems associated with silicone breast implants. Data are scarce about the durability of the silicone shell, and the life span of this device is unknown. The purpose of this study was to investigate the strength of silicone breast implants. Thirty implant shells were subjected to mechanical testing. Twenty-nine of the shells were tested after explanation, and one unused implant served as a control to validate the testing method. Implantation time varied from 4 months to 20 years, and all shells were tested, regardless of condition. Fourteen implant shells were intact, eight were leaking, and seven were ruptured. All ruptured implants had been in place for 10 years or longer. The breaking force of all excised shell specimens ranged from 2.6 to 22.4 N (0.6 to 5.0 lb.). Specimens from the control "high performance" shell required 15.5 to 25.6 N (3.5 to 5.8 lb) of force to fail. The weakest group was from thin-shelled implants between 10 and 16 years of age. More than half these specimens failed with less than 1 lb of force. The average breaking force of ruptured shell material was less than that of intact shells. A comparison of strength data in this study with manufacturers' data suggests that breaking force is dependent on implant type, shell thickness, and implantation time.     

Absence of longitudinal changes in rheumatologic parameters after silicone breast implantation: a prospective 13-year study

There have been numerous questions regarding the association of polysiloxane with connective tissue disease and alteration of host immune response. C-reactive protein, rheumatoid factor, and anti-streptolysin-O titers were measured in 218 patients. These studies are routinely used in the diagnosis of autoimmune disease and mixed connective tissue disease. This prospective study has been in progress since 1985. The first patients were seen in July of 1985, and those individuals willing to participate were followed from 1985 to 1998. The implants included saline-filled elastomer shells and polysiloxane gel-filled elastomer shells. These groups were examined separately and in combination for changes between preoperative and postoperative states. In each instance, there was no statistical increase or decrease. Each patient underwent a physical examination and completed a questionnaire focusing on signs and symptoms of autoimmune and connective tissue diseases. The laboratory data and subjective clinical results demonstrated no significant differences between a nonimplanted group versus the saline group alone, the gel group alone, or the combined groups. The data failed to suggest any causal relationship between implants and autoimmune or connective tissue diseases over the study period of 13 years (since 1985).     

Observation on women with breast implants

The controversy over silicone breast implants continues. This review considers evidence on both sides of the issue. Clinical observations suggests consistent chronic fatigue, muscle pain, joint pain, lymphadenopathy, peripheral neuritis and bladder dysfunction syndrome. Epidemiologic studies of defined connective tissue diseases do not show an association, but some studies show a statistical increase in prevalence of symptoms. The author believes symptomatic women should consider having the breast implants removed and not replaced.     

Total versus partial musculofascial coverage for steroid-containing double-lumen breast implants in augmentation mammaplasty

The use of intraluminal steroids in double-lumen breast implants is effective in preventing fibrous capsular contraction around the implant. This technique has not been accepted widely, however, and remains controversial primarily because steroid-related complications, including extrusion, late inferior migration, and atrophy of the skin, have been associated with their use. This nonrandomized retrospective study of 76 patients (146 breasts) who underwent submuscular augmentation of the breast through inframammary and periareolar incisions compares results after total musculofascial coverage of the implant with partial muscle coverage of the implant. In patients with partial muscle coverage of the implant, 7.8% steroid-related complications were observed. In the group with total musculofascial coverage of the implant, no steroid-related complications and no symptomatic contractions of the capsule were observed. Our study suggests that total musculofascial coverage provides a statistically significant margin of protection from steroid-related complications compared with techniques using only partial muscle coverage of the implant in patients who underwent cosmetic augmentation mammaplasty.     

Breast implants and risk of neurologic disease: a population-based cohort study in Sweden

OBJECTIVE: To examine the risk of neurologic disorders among women with breast implants. BACKGROUND: Case reports in the literature have raised concern about a possible link between silicone breast implants and some types of neurologic disorders, but there is a dearth of epidemiologic studies in this area. METHODS: Through the nationwide Swedish hospital discharge register, we identified a population-based cohort of 7433 women with breast implants. A similarly identified cohort of 3351 women who underwent breast reduction surgery served as a comparison. The women were followed from 1972 (or date of breast surgery if it occurred later) through 1993 by means of record linkages and review of inpatient medical records. Ratios of observed to expected numbers, and relative risks (RR) with 95% confidence intervals (CI), were calculated as measures of the risk of neurologic diseases among women with implants. RESULTS: A direct comparison of the exposed (implant) versus comparison (breast reduction) groups, after exclusion of patients with pre-existing disease or incorrect neurologic diagnoses, showed no excess risk among implant patients (RR = 0.8; 95% CI = 0.5 to 1.4). When external rates derived from the background population were used as comparison, we found a small, statistically nonsignificant excess of neurologic disorders both in the breast implant (RR = 1.3; 95% CI = 0.9 to 1.9) and the breast reduction (RR = 1.5; 95% CI = 0.9 to 2.4) cohorts. CONCLUSION: Our results provide no support for the conjecture that breast implants cause neurologic disease.     

Ruptured or intact: what can linear echoes within silicone breast implants tell us?

OBJECTIVE: During sonographic evaluation of silicone breast implants for possible rupture, we have frequently encountered several patterns of linear echoes within the implants. To our knowledge, the significance of this finding has not been established in the literature. The purpose of this study was to determine whether internal echoes are significant in predicting implant rupture. SUBJECTS AND METHODS: Thirty-three patients with 64 silicone implants were prospectively entered into a study that included gray-scale sonography of the implants and subsequent surgical removal. Echo patterns within the implants were retrospectively evaluated on hard-copy films and compared with the integrity of the implant at surgery. RESULTS: Three categories of internal echo patterns were identified: "thick linear echoes." "thin linear echoes," and "commas." One or more of these echo patterns were seen in 57 (89%) of the 64 implants. Thick linear echoes were seen in 23 (36%) of the 64 implants, thin linear echoes were seen in 33 (52%) of the 64 implants, and commas were seen in 47 (73%) of the 64 implants. All echo patterns were seen in intact and ruptured implants with nearly equal frequency. We found no statistical significance for any echo pattern in predicting whether an implant was ruptured or intact. Of the 64 implants, four were entirely free of internal echoes. All four implants were intact. CONCLUSION: A variety of linear echoes can be seen in most silicone breast implants on gray-scale sonography. The presence or absence of linear echoes is not useful in predicting implant rupture. Complete absence of internal echoes, while highly predictive of an intact implant, is infrequently seen.