SOFT TISSUE IMPLANTS

AUGMENTATION AND RECONSTRUCTION

BREAST IMPLANTS

INTRODUCTION

The breast consists of milk ducts and glands, surrounded by fatty tissue that provides its shape and soft feel. Skin elasticity also contributes to breast shape. Factors such as pregnancy (when milk glands are temporarily enlarged) and the inevitable effects of gravity as women age combine to stretch the skin, causing the breast to droop

Situated beneath the breast is the pectoralis major muscle (Figure 1). A breast implant can be placed either partially under or over this muscle, depending on the thickness of woman’s breast tissue and its ability to adequately cover the breast implant.

Virtually all breast implants are made of a round or shaped silicone elastomer (rubber) shell, and are now commonly filled with a saline solution (salt water). Saline solution is used to fill the implant because it is similar to the fluids in the body, and will be absorbed by your body should the implant leak or break.

Figure1. Pectoralis major muscle

How does a breast implant work?

The incision for each implant is made at one of three typical sites: under the arm, around the nipple, or within the breast fold. (Figure 2)

If the incision is made under the arm, the surgeon may use a probe fitted with a miniature camera, along with minimally invasive instruments, to create a “pocket” for the breast implant.

The breast implant is then placed either partially under the pectoralis major muscle (sub-muscular), or on top of the muscle and under the glands (sub-glandular).

Figure 2

To permit the smallest possible incision, the implant is typically inserted empty, and then filled with saline. Generally, all saline-filled breast implants are made of a silicone elastomer shell with a filling valve, for filling with the saline solution. However, to better meet each individual woman’s needs, breast implants come in different shapes and sizes.

FDA was given the responsibility for regulating medical devices, such as breast implants, under a law called the Medical Device Amendments of 1976. The law requires manufacturers of new medical devices to show that the devices are safe, effective, and properly labeled before they are allowed on the market. Devices in use before the 1976 law, including saline-filled and silicone gel-filled breast implants, were allowed to stay on the market.

There are three types of breast implants, all of which are intended for breast

augmentation, breast reconstruction, and/or replacement of a breast implant. The saline-filled implant has an external silicone shell and is filled with sterile saline (salt water). The silicone gel-filled implant also has an external silicone shell but is filled with silicone gel. An alternative breast implant may have a different shell material and/or different filler.

Most women with breast implants will experience some local complications such as rupture, pain, capsular contracture (a tightening of the scar tissue or capsule the body forms around the breast implant), disfigurement, and serious infection. These may lead to nonsurgical medical treatments and repeat surgeries.

Important factors when deciding to have implants:

Breast implants are not considered lifetime devices and that breast implantation may not be a one-time surgery. The patient may need additional surgery (ies) and doctor visits. She also may have surgery to remove the implant with or without replacement sometime.
Many of the changes to the breast following implantation are irreversible. If the patient later chooses to have the implant(s) removed, she may experience dimpling, puckering, wrinkling, loss of breast tissue, or other cosmetic changes of the breast.
Breast implants may affect the ability to breast-feed. Also, breast implants will not prevent the breast from sagging after pregnancy.
With breast implants, routine screening mammography will be more difficult, and the patient will need to have additional views, which means more time and radiation.

Availability of Implants:

Silicone Gel-Filled Breast Implants

On April 10, 1991, FDA asked the manufacturers to submit evidence in a pre-market approval (PMA) application that silicone gel-filled breast implants were safe and effective. However, they were unable to provide FDA with this information. Without enough data on safety and effectiveness, FDA determined that silicone gel-filled breast implants could not be approved. Therefore, silicone gel-filled breast implants were removed from the open market. However, silicone gel-filled implants are available to women through the following FDA-approved studies:

an adjunct study
an investigational device exemptions (IDE) study

An adjunct study is a study developed for continued availability of silicone-gel breast implants for a public health need. In April 1992, after a careful evaluation of the public health need, the alternatives to silicone gel-filled breast implants, and the risks, FDA concluded that silicone gel-filled breast implants should continue to be available for women seeking breast reconstruction or revision of an existing breast implant. Accordingly, the adjunct study was developed to make silicone gel-filled breast implants available for reconstruction and revision patients and to collect short-term complication

data. Eligible women include those who have had breast cancer surgery, a severe injury to the breast, a birth defect that affects the breast, or a medical condition causing a severe breast abnormality. Additionally, those who need to have an existing implant replaced for medical reasons, such as rupture of the implant, are also eligible. Women who want silicone gel-filled implants for breast augmentation (cosmetic reasons) cannot be enrolled in the adjunct studies. According to the adjunct study protocols, each woman will be followed for at least five years. An IDE study is a clinical study that must be reviewed and approved by FDA to help assure that the resulting data will be meaningful and that patients will not be exposed to unreasonable risks.

Saline-Filled Breast Implants

The manufacturers of saline-filled breast implants were notified by FDA in January 1993 that the agency would require data on their products' safety and effectiveness. While the manufacturers were conducting the required studies, saline-filled breast implants remained on the market.

On August 19, 1999, FDA asked the manufacturers to submit evidence in a PMA (pre-market approval) that saline-filled breast implants were safe and effective. On March 1-3, 2000, FDA’s General and Plastic Surgery Devices Panel met to review PMAs for saline-filled breast Some of the manufacturer’s products were considered eligible. One wants to receive an implant should enroll in an IDE study.

Alternative Breast Implants

Currently, there are no alternative breast implants approved for marketing. As an investigational device, an alternative breast implant can be made available only through an IDE study.

To date, there is one approved IDE for an alternative breast implant called the

Trilucent™; however, there is no new patient enrollment in this IDE.

In 1992 a soybean oil-filled implant, Trilucent™, (Lipomatrix Inc, Neuchatel, Switzerland) was developed and has been available for clinical use in Europe since 1993.

A proportion of women preferred a radiolucent implant to reduce interference with mammography. Longer clinical follow-up of the Trilucent™ implant is awaited with interest. In March 1999, due to the discussions between the manufacturers, the Medical Devices Agency and the NHS executive, Trilucent TM implants were voluntarily withdrawn from the market. Concerns centred around the stability of the lipid oil used as a filler in the wake of anecdotal reports of unilateral breast swelling associated with inflammation which, when explored, revealed a ruptured

implant, the capsule being filled with opaque oil with a rancid smell.

THE SURGERY

General Description of Breast Implant Surgery

Breast implant procedures can be performed on an outpatient (not hospitalized) basis or at a hospital. Breast implant surgery can be done under local anesthesia or under general anesthesia. Breast implant surgery can last from one to several hours depending on whether the implant is inserted behind (sub muscular)

or in front of (sub glandular) the chest muscle and whether surgery is performed on one or both breasts. If the surgery is done in a hospital, the length of the hospital stay will vary according to the type of surgery, the development of any postoperative complications, and patient’s general health.

Expectations - Reconstruction or Augmentation

The consideration of breast implants, for reconstruction or for augmentation, should be based on realistic expectations of the outcome

The results will depend on many individual factors, such as

patient’s overall health
chest structure and body shape
healing capabilities (which may be hindered by radiation and chemotherapy,

smoking, alcohol, and various medications

bleeding tendencies/likelihood

The patient is given general or local anesthesia, and in most cases, antibiotics. The surgery may last from 1-2 hours for augmentation to several hours for reconstruction or revision. Scarring is a natural outcome of surgery, and the doctor can describe the location, size, and appearance of the scars that patient can expect to have. For most women, scars will fade over time to thin lines, although the darker the skin, the more prominent the scars are likely to be.

Postoperative Care

The doctor should describe the usual postoperative (after surgery) recovery process, the possible complications that can arise, and the expected recovery period. Following the operation, as with any surgery, some pain, swelling, bruising, and tenderness can be expected. These complications may last for a month or longer, but they should disappear with time.

Medications for pain and nausea can be prescribed. Some women may experience bleeding and some may experience fever, warmth, or redness of the breast, or other symptoms of infection. The patient should be told about wound healing and how to care for the wound. Drains may be used for a few days.

Post-operative care may involve the use of a post-operative bra, compression bandage, or jog bra for extra support and positioning while the patient heals. At the doctor’s recommendation, the patient will most likely be able to return to work within a few days, although she should avoid any strenuous activities that could raise the pulse and blood pressure for at least a couple of weeks. The doctor may also recommend breast massage exercises.

The patient should ask her doctor about a schedule of follow-up examinations, limits on her activities, precautions she should take, and when she can return to her normal routine.

For women with breast cancer:

The following issues should be considered for women with breast cancer:

- The physical and cosmetic results with breast implants may be affected by chemotherapy, radiation therapy, or any other factor that significantly alters the healing process.

- Skin necrosis (cell death) may occur because circulation to the remaining tissue has been changed by a mastectomy (breast removal). Also, skin necrosis may be increased as a result of radiation treatment.

- It usually takes more than one operation to achieve the desired cosmetic outcome, especially if this procedure includes building a new nipple.

Breast Reconstruction with Breast Implants

The surgeon will decide whether the patient’s health and medical condition makes her an appropriate candidate for breast implant reconstruction. Women with larger breasts may require reconstruction with a combination of a tissue flap and an implant. The surgeon may recommend breast implantation of the opposite, uninvolved breast in order to make them more alike (maximize symmetry) or he/she may suggest breast reduction (reduction mammoplasty) or a breast lift (mastopexy) to improve symmetry. Mastopexy involves removing a strip of skin from under the breast or around the nipple and using it to lift and tighten the skin over the breast. Reduction mammoplasty involves removal of breast tissue and skin.

Timing of Breast Implant Reconstruction

The breast reconstruction process may begin at the time of the mastectomy (immediate reconstruction) or weeks to years afterwards (delayed reconstruction). Immediate reconstruction may involve placement of a breast implant, but typically involves placement of a tissue expander, which will eventually be replaced with a breast implant. It is important to know that any type of surgical breast reconstruction may take several steps to complete.

Two potential advantages to immediate reconstruction are that patient’s breast reconstruction starts at the time of the mastectomy and that there may be cost savings in combining the mastectomy procedure with the first stage of the reconstruction. However, there may be a higher risk of complications such as deflation with immediate reconstruction, and your initial operative time and recovery time may be longer. A potential advantage to delayed reconstruction is that patient can delay her reconstruction decision and surgery until other treatments, such as radiation therapy and chemotherapy, are completed. Delayed reconstruction may be advisable if the surgeon anticipates healing problems with the mastectomy, or if the patient just needs more time to consider her options.

There are medical, financial, and emotional considerations to choosing immediate versus delayed reconstruction. It should be discussed with the surgeon, plastic surgeon, and oncologist, the options available in the patient’s individual case.

Surgical Considerations

1) Immediate Reconstruction:

- One-stage immediate reconstruction with a breast implant (implant only).

- Two-stage immediate reconstruction with a tissue expander followed by delayed reconstruction several months later with a breast implant.

2) Delayed Reconstruction:

- Two-stage delayed reconstruction with a tissue expander followed several months later by replacement with a breast implant.

One-Stage Immediate Breast Implant Reconstruction

Immediate one-stage breast reconstruction may be done at the time of the mastectomy. After the general surgeon removes the breast tissue, the plastic surgeon will then implant a breast implant that completes the one-stage reconstruction.

Two-Stage (Immediate or Delayed) Breast Implant Reconstruction

Breast reconstruction usually occurs as a two-stage procedure, starting with the placement of a breast tissue expander, which is replaced several months later with a breast implant. The tissue expander placement may be done immediately, at the time of the mastectomy, or be delayed until months or years later.

Figure 5. Breast tissue removed Figure 6. Expander, inserted and filled

Tissue Expansion

During a mastectomy, the surgeon often removes skin as well as breast tissue, leaving the chest tissues flat and tight. To create a breast shaped space for the breast implant, a tissue expander is placed under the remaining chest tissues. The tissue expander is a balloon-like device made from elastic silicone rubber. It is inserted unfilled, and over time, sterile saline fluid is added by inserting a small needle through the skin to the filling port of the device. As the tissue expander fills, the tissues over the expander begin to stretch, similar to the gradual expansion of a woman's abdomen during pregnancy. The tissue expander creates a new breast shaped pocket for a breast implant. Tissue expander placement usually occurs under general anesthesia in an operating room. Operative time is generally one to two hours. The procedure may require a brief hospital stay, or be done on an outpatient basis. The patient resumes normal daily activity after two to three weeks.

Placing the Breast Implant

After the tissue expander is removed, the breast implant is placed in the pocket. The surgery to replace the tissue expander with a breast implant (implant exchange) is usually done under general anesthesia in an operating room. It may require a brief hospital stay or be done on an outpatient basis.

Figure 7. Post mastectomy, tissue expander and breast implant reconstructions

Breast Reconstruction Without Implants: Tissue Flap Procedures

The breast can be reconstructed by surgically moving a section of skin, fat, and muscle from one area of the body to another. The section of tissue may be taken from such areas as abdomen, upper back, upper hip, or buttocks. The tissue flap may be left attached to the blood supply and moved to the breast area through a tunnel under the skin (a pedicled flap), or it may be removed completely and reattached to the breast area by microsurgical techniques (a free flap). Flap surgery requires a hospital stay of several days and generally a longer recovery time than implant reconstruction. Flap surgery also creates scars at the site where the flap was taken and possibly on the reconstructed breast. However, flap surgery has the advantage of being able to replace tissue in the chest area. This may be useful when the chest tissues have been damaged and are not suitable for tissue expansion. Another advantage of flap procedures over implantation is that alteration of the unaffected breast is generally not needed to improve symmetry. The most common types of tissue flaps are the TRAM, transverse rectus abdominus musculocutaneous flap which uses tissue from the abdomen and the Latissimus dorsi flap, which uses tissue from the upper back. It is important to be aware that flap surgery, particularly the TRAM flap, is a major operation and more extensive than mastectomy operation. It requires good general health and strong emotional motivation. Also, if the patient is very thin, she may not have enough tissue in the abdomen or back to create a breast mound with this method.

The TRAM Flap (Pedicle or Free)

During a TRAM flap procedure, the surgeon removes a section of tissue from the abdomen and moves it to thechest to reconstruct the breast. The TRAM flap is sometimes referred to as a "tummy tuck" reconstruction because it may leave the stomach area flatter.

The Latissimus Dorsi Flap With or Without Breast Implants

During a Latissimus Dorsi flap procedure, the surgeon moves a section of tissue from back to the chest to reconstruct the breast. Because the Latissimus Dorsi flap is usually thinner and smaller than the TRAM flap, this procedure may be more appropriate for reconstructing a smaller breast.

Comparison:

Two major breast reconstruction options are currently available. Autologous reconstruction is most commonly performed using a transverse rectus abdominus myocutaneous (TRAM) flap. An alternative procedure is placement of tissue expander, which can be replaced with a prosthetic implant after serial expansions with saline solution. The expander/implant technique is often used for patients who are not considered good surgical candidates for autologous reconstruction or for those who prefer a simpler reconstruction alternative.

Data on the cosmetic outcome and complication rates for reconstruction in the previously or subsequently irradiated breast/chest wall region are limited. Prior studies have suggested a significant risk of complications and adverse cosmetic outcome for patients undergoing expander / implant reconstruction and radiotherapy. Autologous reconstruction with radiotherapy appears to be better tolerated, although the timing of reconstruction may have an impact on the complication rates. Relatively small patient numbers and/or a lack of mature follow-up, particularly in the expander / implant subgroup; have limited many of these reports.

Figure 8. Actuarial complication rate and actual re-operation rates based on type of reconstruction: TRAM flap vs. Expander / Implant.

The tolerance and cosmetic outcome of breast reconstruction for breast cancer patients in previously or subsequently irradiated sites depend significantly on the type of reconstruction used. Those who receive autologous reconstruction with the TRAM flap have fewer complications, a reduced need for re-operation, and improved cosmesis compared with those receiving E/I reconstruction.

To clarify which of these factors may be truly predictive, larger prospective studies are required.

Currently, for patients who have received or will receive chest wall radiotheraphy as part of their breast cancer treatment and express interest in breast reconstruction, our recommendation is to encourage autologous reconstruction for those who are medically fit for this procedure. This can be performed at the time of mastectomy or can be delayed until after radiotheraphy has been administered, depending on the preference of the patient and physician. For those who are not candidates for autologous reconstruction or strongly prefer a simpler surgical reconstruction alternative, the E/I option can be explored and discussed. These patients should be appropriately counseled regarding the cosmetic results and increased complication rate with this procedure in combination with radiotheraphy.

Silicone

Silicones are synthetic polymers that have a linear, repeating silicon-oxygen backbone. Certain organic groups can be used to link two or more of these silicon oxygen backbones and the nature and extent of this cross-linking enables a wide variety of products to be manufactured. The most important materials used in medical implants are fluids, gels and rubbers (elastomers) whose physical and chemical properties include a high degree of chemical inertness, thermal stability and resistance to oxidation. Silicone fluids are usually linear chains of PDMS, which have a wide range of chain lengths and molecular masses. They are virtually insoluble in water. Silicone gels have lightly cross-linked polysiloxane networks, swollen with PDMS fluid to produce a cohesive mass. The degree of cross-linking and amount of fluid affects the physical properties of the gel and the rate at which fluid "bleeds" from it. Once suitably cross-linked, silicone gels retain their form without external containment. Silicone elastomers are extensively cross-linked and contain little free

PDMS fluid. The barrier coating of breast implant shells is a special silicone elastomer, which is selected specifically to minimize migration of PDMS from the implants. The tensile strength and tear resistance of silicone elastomers may be increased by addition of amorphous silica.

The Institute of Medicine completed its independent review of all past and ongoing

scientific research study of silicone breast implant safety in June 1999. Among the major findings from this study were that local complications with silicone breast implants were the primary safety issue with breast implants, and that these have not been well studied. In addition, immunological studies in animals have demonstrated that silicones have not been shown to stimulate a specific antibody response, are unlikely to stimulate cell mediated immunity under clinical use conditions, and have no adverse effect on host-resistance to infection. Animal studies thus provide no immunological reason for concern over the use of silicone gels in implants. Studies have also concluded that there was no evidence of an increased risk of connective tissue disease in patients who had undergone silicone gel breast implantation.

Silicone gel-filled breast implants have been available since 1963 and it is estimated

that more than one million women have had breast implants, either for cosmetic augmentation mammoplasty (breast enlargement) or breast reconstruction following mastectomy. Whilst many would regard breast augmentation for cosmetic reasons as frivolous, it is a fact that many women feel a deep personal need for breast enhancement to improve their sense of wholeness and self esteem and a successful prosthetic augmentation mammoplasty has significantly improved the quality of life of the vast majority of women who have undergone such surgery.

The original device was a thick, smooth-surfaced envelope of silicone rubber (elastomer) filled with a silicone gel. As with all medical products the implant has evolved and improved with experience.

Life of Implant and Fate of Gel

• All gel-filled prostheses will undergo ‘gel-bleed’ after some time. This leakage of silicone is usually small in amount and is mostly incorporated in the scar capsule; it is possible that minute quantities are transported to lymph nodes by macrophages.

A smaller number of prostheses have a visible capsule rupture with significant outlet of gel which is again contained by a fibrous reaction but may have migrated a distance into the surrounding tissues before it is contained as a ‘granuloma’.

• Gel-filled implants may have a definitive life span of approximately ten years and it is recommended they be replaced if symptoms are produced or there is evidence of implant rupture.

All degrees of gel-bleed are more common and occur earlier in those prostheses produced in the late 70s and early 80s. There is minimal gel-bleed with later improvements in manufacture.

• It is possible that some minute amount of silicone escapes into the body generally. There is no good scientific evidence that this small amount poses any health risk. This silicone joins the silicone present in the bodies of all of us; since free silicone can, and does, enter the body from numerous other sources. All humans carry silicone in their bodies. It is considered one of the least reactive materials used in medical devices. It is used as a lubricant in intravenous tubing, disposable needles and syringes, and in stoppered vials for various medications. Silicone is used as an anti-foaming agent in blood transfusions and cardiac bypass machines. It is present in drinking water and is used in some processed foods, skin creams, cosmetics, polishes and hair sprays. Liquid silicone is present in significant amounts in many antacids, and in babies’ anticolic remedies. It has multiple avenues of access to the body. Solid form silicone is used in a variety of devices implanted into the body, including pacemakers, prosthetic joints, hydrocephalus shunts, penile and testicular implants, and implanted drug-delivery systems.

• There is no convincing evidence that patients with silicone-gel filled prostheses, whether leaking or not, have an increased incidence of systemic disease, including autoimmune disease (Sjogren’s syndrome, scleroderma, polymyositis or rheumatoid arthritis).

• There is no good evidence that silicone or free silicone-gel in the tissues increases the risk of breast cancer or influences the course of the disease.

• There is no evidence that the polyurethane coating that was placed on the surface of some prostheses is in any way carcinogenic for humans, even though the manufacturers have withdrawn such products from the market voluntarily.

• There is some evidence that self-examination of the breast and palpation of early breast lumps is made easier after prosthetic augmentation mammoplasty because the breast tissue is brought forward on the chest wall.

• Free silicone in the breast can produce a palpable lump (silicone granuloma) which may be difficult to distinguish from other breast pathology without a biopsy.

There is no evidence that silicones have any teratogenetic or mutagenic effect. All animal studies to date show no evidence of birth defects. Silicone implants do not interfere with lactation and many patients successfully nurse their infants after augmentation mammoplasty. The possibility of free silicone in milk is being investigated but certain medicines approved for infants do contain medical grade silicone (methicone, simethicone, dimethicone). Although entry of silicone into the ductal system has been observed it is exceedingly rare and there is no convincing evidence that this is detrimental to the feeding infant, or exposes the child to future illness.

BREAST IMPLANT RISKS

Due to the Institute of Medicine (IOM), local complications with silicone breast implants were the primary safety issue with breast implants.

Complications may have risks themselves, such as pain, disfigurement, and serious infection and they may lead to medical and surgical interventions, such as re-operations, that have risks.

Second, risks accumulate over the lifetime of the implant, but quantitative data on this point are lacking for modern implants and deficient historically.

Third, information concerning the nature and the relative high frequency of local complications and re-operations is an essential element of adequate informed consent for women undergoing breast implantation.

There are risks or complications associated with any surgical procedure, such as the effects of anesthesia, infection, swelling, redness, bleeding, and there are complications specific to breast implants.

Capsular contracture is when the scar tissue or capsule that normally forms around the implant tightens and squeezes the implant. It may be more common following infection, hematoma (collection of blood), and seroma (collection of watery portion of blood). Additional surgery may be needed to correct the capsular contracture. This surgery ranges from removal of the implant capsule tissue to removal (and possibly replacement) of the implant itself. Capsular contracture may happen again after this additional surgery. A retrospective study by Gabriel et al. indicated that 131 of 749 (17.5%) women had at least one surgical procedure over an average of 7.8 years because of capsular contracture. This would not include capsular contracture that may have been severe but did not result in surgery. This study included women who had implants for cosmetic and reconstruction purposes, most of whom had silicone gel-filled breast implants.

The length of the implantation time is the most important factor in the development of capsular contracture. There is a correlation between the symptomatology of contracture (such as breast firmness) and histological findings (such as capsular thickness). Siggelkow et. al. could not find a significant relationship between the amount of silicone in the implant environment and the presence of histiocytic inflammation, but could find signs of a moderate, persistent inflammatory reaction especially in smooth long-term implants. Qualitative and quantitative analyses of the inflammatory processes in the environment of the implant and their link to fibrotic activation and collagen deposition would be of major interest

Some implants deflate or rupture in the first few months after being implanted and some deflate after several years; others are intact 10 or more years after the surgery.

a. Silicone Gel-Filled Breast Implants - When silicone gel-filled implants rupture, some women may notice decreased breast size, nodules (hard knots), uneven appearance of the breasts, pain or tenderness, tingling, swelling, numbness, burning, or changes in sensation. Some may unknowingly experience a rupture without any symptoms (i.e., “silent rupture”). Magnetic resonance imaging (MRI) with equipment specifically designed for imaging the breast may be used for evaluating patients with suspected rupture or leakage of their silicone gel-filled implant. Silicone gel, which escapes the fibrotic capsule surrounding the implant, may migrate away from the breast. The free silicone may cause lumps called granulomas to form in the breast or other tissues where the silicone has migrated, such as the chest wall, armpit, arm, or abdomen.

Plastic surgeons usually recommend removal of the implant if it has ruptured, even if the silicone is still enclosed within the scar tissue capsule, because the silicone gel may eventually leak into surrounding tissues. Women with silicone gel-filled breast implants had a MRI examination of their breasts to determine the status of their current breast implants. Due to the results, 69% of the 344 women had at least one ruptured breast implant, 21% had extra-capsular silicone gel in one or both breasts.

Factors that were associated with rupture included increasing age of the implant, the implant manufacturer, and sub-muscular rather than sub-glandular location of the implant. Robinson et al. studied 300 women who had their implants for 1 to 25 years and had them removed for a variety of reasons. Visible signs of rupture in 51% of the women studied were found. Severe silicone leakage (silicone outside the implant without visible tears or holes) was seen in another 20%. Robinson et al. also noted that the chance of rupture increases as the implant ages.

b. Saline-Filled Breast Implants – Saline-filled breast implants deflate when the saline solution leaks either through an unsealed or damaged valve or through a break in the implant shell. Implant deflation can occur immediately or progressively over a period of days and is noticed by loss of size or shape of the implant. Some implants deflate or rupture in the first few months after being implanted and some deflate after several years. You should also be aware that the breast implant may wear out over time and deflate. Additional surgery is needed to remove deflated implants.

A retrospective study of saline breast implants by Gutowski et al. indicates that 10.1% of women followed for an average of 6 years had at least one implant deflated.

There is a high chance that the patient will need to have additional surgery at some point to replace or remove the implant(s) due to problems such as deflation, capsular contracture, infection, shifting, and calcium deposits. Many women decide to have the implants replaced, but some women do not. Those who do not have their implants replaced may have cosmetically undesirable dimpling and/or puckering of the breast following removal of the implant.

In a prospective clinical study of saline-filled breast implants the cumulative, 3-year, by patient rates of a first occurrence of additional surgeries were 13% for the 1264 augmentation patients and 40% for the 416 reconstruction patients.

In a prospective clinical study of saline-filled breast implants the cumulative, 3-year, by patient rates of a first occurrence of additional surgeries were 21% for the 901 augmentation patients and 39% for the 237 reconstruction patients.

A retrospective study by Gabriel et al. shows that 24% of women with breast implants experience adverse events resulting in surgery during the first five years after implantation (silicone and saline implants were studied together).

According to this study, about 1 in 3 women getting breast implants for reconstruction may need a second surgery within five years, and about 1 in 8 women getting breast implants for augmentation may need a second surgery within five years. These additional surgeries may result in the loss of breast tissue.

Women may feel pain of varying severity (degrees) and duration (length of time) following breast implant surgery. In addition, improper size, placement, surgical technique, or capsular contracture may result in pain associated with nerve entrapment or interference with muscle motion.

Dissatisfying results such as wrinkling, asymmetry, implant displacement (shifting), incorrect size, unanticipated shape, implant palpability, scar deformity, hypertrophic (irregular, raised scar) scarring, and/or sloshing may occur. Careful surgical planning and technique can minimize but not always prevent such results. Additionally, for saline-filled implants that have a valve, the patient should be able to feel the valve of the implant with her hand.

Repeated surgeries to improve the appearance of the breasts and/or to remove ruptured or deflated prostheses may result in an unsatisfactory cosmetic outcome.

Infection can occur with any surgery. Most infections resulting from surgery appear within a few days to weeks after the operation. However, infection is possible at any time after surgery. Infections with an implant present are harder to treat than infections in normal body tissues. If an infection does not respond to antibiotics, the implant may have to be removed, and another implant may be placed after the infection has cleared up. In rare instances, Toxic Shock Syndrome has been noted in women after breast implant surgery, and it is a life-threatening condition. Symptoms include sudden fever, vomiting, diarrhea, fainting, dizziness, and/or sunburn-like rash.

Hematoma is a collection of blood inside a body cavity, and seroma is a collection of

the watery portion of the blood around the implant or around the incision. Postoperative hematoma and seroma may contribute to infection and/or capsular contracture. Swelling, pain, and bruising may result. If a hematoma occurs, it will usually be soon after surgery; however, this can also occur at any time after injury to the breast. While the body absorbs small hematomas and seromas, large ones will require the placement of surgical drains for proper healing. A small scar can result from surgical draining. Implant deflation/rupture can occur from surgical draining.

Feeling in the nipple and breast can increase or decrease after implant surgery. The range of changes varies from intense sensitivity to no feeling in the nipple or breast following surgery. Changes in feeling can be temporary or permanent and may affect sexual response or the ability to nurse a baby.

Deposits of calcium can be seen on mammograms and can be mistaken for possible cancer, resulting in additional surgery to biopsy and/or remove the implant to distinguish these deposits from cancer. Calcium deposits may be felt as nodules (hard knots) under the skin around the implant.

In some cases, the incision site fails to heal normally or takes longer to heal.

An unstable or compromised tissue covering and/or interruption of wound healing may result in extrusion of the implant, which is when the breast implant comes through the skin. The additional surgery needed to correct this complication can result in unacceptable scarring or loss of breast tissue.

Necrosis is the formation of dead tissue around the implant. This may prevent wound healing and require surgical correction and/or implant removal. Permanent scar and/or deformity may occur following necrosis. Factors associated with increased necrosis include infection, use of steroids in the surgical pocket, smoking, chemotherapy / radiation, and excessive heat or cold therapy.

The pressure of the breast implant may cause the breast tissue to thin and shrink. This can occur while implants are still in place or following implant removal without replacement.

Interference with mammography due to breast implants may delay or hinder the early detection of breast cancer either by hiding suspicious lesions (wounds or injuries or tumors) or by making it more difficult to include them in the image. Implants increase the difficulty of both taking and reading mammograms. Some women who undergo reconstruction will have some breast tissue remaining, and some have all of their breast tissue removed. It is important that a woman with breast tissue remaining continue to have mammography of that breast, as well as of the other breast, to detect breast cancer.

Mammography requires breast compression (hard pressure) that could contribute to implant rupture. In addition to special care taken by the technologist to reduce the risk of implant rupture during this compression, other techniques are used to maximize what is seen of the breast tissue during mammography. These techniques are called breast implant displacement views, Eklund displacement views, or Eklund views, after the radiologist who developed them. These special implant displacement views are done in addition to those views done during routine mammograms.

Because of the extra views and time needed, women with implants should always inform the receptionist or scheduler that they have breast implants when making an appointment for mammography. They should also tell the radiology technologist about the presence of implants before mammography is performed. This is to make

sure that the technologist uses these special displacement techniques and takes extra care when compressing the breasts to avoid rupturing the implant.

Also, a radiologist may find it difficult to distinguish calcium deposits in the scar tissue around the implant from a breast tumor when he or she is interpreting the mammogram. Occasionally, it is necessary to remove and examine a small amount of tissue (biopsy) to see whether or not it is cancerous. This can frequently be done without removing the implant.

Sometimes after breast implant surgery, the patient may begin producing breast milk. In some cases, the milk production stops spontaneously or when medication is given to suppress milk production. In other cases, removal of the implant(s) may be needed.

Most of the health concerns about breast implants are related to silicone gel. Even if a silicone gel-filled breast implant does not rupture, small amounts of the silicone fluid or oil may bleed out of the implant and migrate into the surrounding tissue. There has been concern that this escaped silicone fluid or oil might cause harmful effects, including connective tissue disease and related disorders and/or cancer.

The body’s immune system is the network of cells that protect against infectious diseases. CTDs and related disorders of the body's immune system are related to the connective tissues of the body, which include fibrous tissues, cartilage, and bone that support body structures and bind body parts together. Some CTDs are autoimmune diseases that occur when a woman’s immune system attacks her own

Disorders that are not autoimmune include

Some women with breast implants have experienced the diseases and/or disorders listed above, as well as a variety of signs and symptoms that could be related to the immune system. However, this is not considered a defined disorder. They include;

new disease which is related to silicone and have called the disease "human adjuvant disease," "silicone related syndrome," "atypical disease," or other names. The researches done show that there does not appear to be even suggestive evidence of a novel [new] syndrome in women with breast implants. So, it is unclear at this time whether the signs and symptoms experienced by these women are related to their implants. In some cases, women have reported fewer symptoms after the implants were removed.

Studies have shown that some women with silicone gel-filled breast implants produced antibodies to their own collagen (a connective tissue protein), but we do not know how often these antibodies occur in the general population, and there are no data that show these antibodies cause CTDs and related disorders.

There are reports of women with implants who have other auto-antibodies. However, the presence of these antibodies does not mean that a woman has an increased risk of actually developing a CTD or related disorder.

When the completed studies are considered together, the risk of developing a typical

Without a group of women without implants who are of similar age, health, and social

status and followed for a long time (such as 10-20 years), a relationship between implants and these diseases cannot conclusively be made. Also none of the studies has been large enough to rule out the possibility that the implants could cause CTD or a related disorder in a small subset of women who have them. In other words, these studies do not resolve the question of whether the variety of signs and symptoms some women report might be related to their implants.

The Institute of Medicine report indicates that breast cancer is no more common in women with implants than those without implants. At this time, there is no scientific evidence that silicone gel-filled breast implants can increase the risk of other cancers in women, but this possibility cannot be completely ruled out because the studies to evaluate the risk of other cancers have not been done.

About 10% of women with breast implants received the polyurethane foam-coated type until they were taken off the market in 1991 because of concerns that the coating might increase the risk of breast cancer. This coating released small quantities of the chemical called TDA (2,4-toluenediamine) that has been shown to cause cancer in animals. Because of this concern, the manufacturer of the coated implants, Bristol-Myers Squibb Company, analyzed the urine of women with these devices for TDA.20

Researchers found TDA in the urine but in such tiny amounts that the risk of cancer from the polyurethane foam-coated implants is only about l in a million over a woman's lifetime. Therefore, it is unlikely that even 1 of the estimated 110,000 women who got the polyurethane foam-covered implants will get cancer as a result of exposure to the TDA. This study supports FDA's recommendation that women with polyurethane foam-covered breast implants should not have them removed based solely on concerns about cancer from TDA. Concerns have also been raised about whether the TDA from the polyurethane-coated implants could increase the risk of cancer to a nursing infant. FDA required the manufacturer to analyze mother's milk for TDA, but the manufacturer was unable to get enough lactating women with these implants to conduct a valid study.

Women of childbearing age who want to breast-feed should be aware of the negative impact of breast implants on breast feeding. One concern is the ability to successfully breast-feed after breast implantation. Some women who undergo breast augmentation can successfully breast feed and some cannot. Women who undergo a mastectomy will be unable to breast-feed on the affected side due to loss of breast tissue and glands that produce milk.

Having an implant may significantly affect the patient’s ability to breast-feed. It is not known if a small amount of silicone may pass from the silicone shell of an implant into breast milk. If this occurs, it is not known what effect it may have on the nursing infant. Although there are no current methods for detecting silicone levels in breast milk, a study by Semple et al. measuring silicon (one component in silicone) levels showed the same levels in breast milk from women with silicone gel–filled implants when compared to breast milk from women without implants.

Concerns have been raised about the potential damaging effects on children born of mothers with implants. The Institute of Medicine report said that the information is insufficient to draw definite conclusions about this issue. In other words, it is not known what effect breast implants may have on a fetus and the nursing infant.

There is some concern, but little information, about possible risks from the silicone material of the shell from the saline-filled and silicone gel-filled breast implants. Another concern relates specifically to saline-filled breast implants. Questions have been raised about the potential for the saline to become contaminated (not sterile) with fungus or bacteria and to be released into the woman's body if her implant deflates or ruptures or if the valve leaks. However, saline-filled implants are now generally filled from a bag and tubing rather than from an open bowl, which should reduce the risk of this complication. Also, the manufacturers have advised doctors against adding any antibacterial, antiseptic, or cleansing agent to the saline as it may

Future Trends

Adipose Tissue Engineering

Ideally, a surgeon prefers to refill the breast envelope with a patient’s own adipose tissue. The contemporary standard of care for breast reconstruction includes utilizing implants or tissue transfer, both of which possess limitations. Resection of tumors in the head and neck, and upper and lower extremities often results in contour defects due to loss of soft tissue, which is largely composed of subcutaneous adipose tissue. Again, a surgeon prefers to use a patient’s own adipose tissue to sculpt contour deformities. There are numerous reconstructive, cosmetic, and correctional indications for the development of clinically translatable strategy with which to restore a volume of adipose tissue.

Tissue engineering, coupled with knowledge gleaned from obesity and diabetes research as well as the amassed clinical experience with fat grafting, possesses the potential to provide surgeons with a source of patient-specific adipose tissue of a predefined volume. This work explores the current state of the art in adipose tissue engineering. The three fundamental components of a tissue construct cells, scaffold, and microenvironment are discussed first.

Adipose Tissue: it is the largest tissue in the body, and is uniquely expendable in that most patients possess excess that can be harvested without creating contour deformities. However, autologous fat transplantation yields poor results, with 40–60% reduction in graft volume.

Figure 12. Overview of proposed adipose tissue engineering strategy for developing a de-novo breast mound.

Adipose tissue is obtained from the patient via liposuction or fat biopsy. From the tissue sample, pre-adipocytes and capillary endothelial cells are isolated via enzymatic digestion and expanded ex vivo. The capillary endothelial cells are finessed to form microvascular networks. The preadipocytes and microvascular network are later placed, along with appropriate angiogenic and adipogenic growth factors, within a biodegradable polymer scaffold. The patient-specific scaffold shape, volume, and the number of cells required are obtained from a virtual breast simulator.

A breast tissue engineering strategy must be patient-specific to be truly clinically translatable. Unlike strategies for organs that can, for the most part, be grown as

“one size fits all,” breast shape and volume vary widely among the patient population. Breast implants, for instance, range from 100 mL to 2 L. Hence, methods must

exist to predetermine design parameters preoperatively such that the final outcome is known a priori. To accomplish this goal, bioengineers, physicians, and computer scientists have combined skill sets to develop a first-generation virtual reality breast simulator (Fig. 6). The current system uses a global parametric deformable model of an ideal breast, and allows the surgeon to manipulate the shape of the breast by varying five key shape variables, analogous to the aesthetic and structural elements surgeons inherently vary during breast reconstruction. The second generation of the virtual reality model is being developed to be truly patient-specific by importing three-dimensional measurements of the surface of the patient’s breast obtained via surface scanning.

Once the cells and growth factors are placed within the scaffold, the entire construct is implanted within the breast envelope following mastectomy. Using microsurgery techniques, the host vascular system is anastomosed with the construct’s microvascular network. As the scaffold degrades, the preadipocytes proliferate and differentiate into adipose tissue. The microvascular system will reorganize accordingly. In essence, the patient becomes her own bioreactor for developing a new breast.

Soft Tissue Augmentation

Tissue engineering strategies for wrinkle and soft-tissue augmentation involve the restoration of localized contour defects. The restoration site for a wrinkle and soft-tissue defect differ in anatomical location

In wrinkle, a deficit in the dermis causes a contour defect that is translated to the epidermis and stratum corneum. Hence, an adipose product would be injected between the dermis and epidermis utilizing contemporary injection techniques.

In a soft-tissue defect, a tissue deficit occurs much deeper in the subcutaneous fat layer, causing a large contour defect that is translated to the dermis, epidermis, and stratum corneum. In addition, adhesion plaques form between the muscle and dermis. Hence, an adipose product would be injected within the subcutaneous fat between the muscle and dermis. During the injection, the adhesion plaques would have to be cleaved. Obvious strategies include injecting hydrogels containing preadipocytes and adipogenic / angiogenic factors. Other strategies may involve

developing a thin, flexible fabric composed of a bio-degradable polymer or polymer blend that can be pre-seeded with pre-adipocytes.

The field of tissue engineering offers great potential in the current limitations of breast reconstruction and soft tissue augmentation following tumor resection. However, the continued progress, and ultimately the clinical translation, of adipose tissue engineering applied to oncologic reconstructive surgery will require the active, synergistic collaboration of bioengineers, life scientists, and oncologic reconstructive surgeons.

Some Statistics

Appendices

authority to regulate medical devices such as breast implants, which were already

July 23, 1976: The FDA General and Plastic Surgery Devices Panel recommended that breast implants be placed in class II, requiring general controls and performance standards. Class II devices require additional measures, called special controls, to control risks. Special controls may include performance standards, postmarket surveillance studies, user education, or other measures. If there is a lack of information about whether a device is safe and effective, it is put into class III, and the highest level of pre-market review is required. Class III devices include innovative (creative), medical breakthrough, and new technology devices, as well as devices with poorly established or questionable safety and effectiveness.

January 19, 1982: Because of some reports of adverse events in the medical

literature, FDA announced a proposal to place breast implants in class III. Class III

June 24, 1988: FDA classified all breast implants into class III. After a prescribed

January - March 1989: An unpublished study showed that polyurethane foam, which was used as a coating on certain types of silicone gel-filled breast implants, would degrade and release 2-toluene diamine (TDA), a chemical known to cause cancer in animals, under conditions of high temperature and alkalinity. FDA requested specific information from the manufacturer about the chemical make up and safety testing of polyurethane foam. Shortly afterwards, the manufacturer of polyurethane-coated breast implants removed them from the market.

May 17, 1990: FDA issued a proposed 515(b) regulation (call for safety and effectiveness data) in the Federal Register on silicone gel-filled implants.

February 1-2, 1991: FDA sponsored a Conference on Silicone in Medical Devices.

This was an exchange of scientific information and views on the applications of silicone in medical devices.

April 10, 1991: FDA published a final 515(b) regulation in the Federal Register that required manufacturers of silicone gel-filled implants to submit PMAs with data showing the safety and effectiveness of the implants by July 9, 1991.

June 1991: FDA required the manufacturer of polyurethane-coated implants to conduct research on the material. In taking this action, FDA made the first use of new post-market surveillance authority under the Safe Medical Devices Act of 1990.

July 31, 1991: The Panel reviewed FDA's risk assessment of polyurethane foam coating. The Panel found that the risk of cancer, if any, appears small and would very likely be outweighed by the surgical risk involved in removing a polyurethane-coated

August 22, 1991: FDA determined that PMAs submitted by three manufacturers of silicone gel-filled implants did not contain sufficient data to warrant a full review.

September 26, 1991: FDA issued a Notice in the Federal Register requiring distribution of information to patients on the risks associated with saline-filled and silicone gel-filled breast implants.

November 12-14, 1991: FDA convened the Panel to consider whether the PMA data received from the manufacturers was sufficient to establish that the silicone gel-filled implants are safe and effective. Despite the lack of data, the Panel voted unanimously to advise FDA that the implants filled a public health need for breast reconstruction and revision for medical or surgical reasons and that the implants should continue to be available while the manufacturers collected additional data.

January 6, 1992: FDA called for a voluntary moratorium on the use of silicone gel-filled implants until new safety information could be thoroughly reviewed by the Panel.

February 18, 1992: The Panel met again to review new information on silicone gel-filled implants. This included case reports of autoimmune diseases, information not included in the manufacturers' original submissions to FDA, and evidence that some early models may have leaked excessively.

March 19, 1992: Dow Corning withdrew from the silicone implant market but continued to supply gel to one implant manufacturer.

April 16, 1992: FDA lifted the voluntary moratorium on breast implants. FDA also announced its decision to allow silicone gel-filled implants on the market only under controlled clinical studies for reconstruction after mastectomy, correction of congenital deformities, or replacement of ruptured silicone gel-filled implants due to medical or surgical reasons. Until the these clinical studies could be submitted and reviewed, FDA authorized temporary limited distribution of silicone gel-filled implants for reconstructive patients on an urgent need basis with a very detailed informed consent form. FDA denied applications for using silicone gel-filled breast implants for augmentation but planned that the manufacturers would later conduct clinical trials that would include a limited number of augmentation patients

July 24, 1992: FDA approved Mentor Corporation’s stage 2 (or adjunct study protocol) for silicone gel-filled implants for reconstruction and revision only.

December 1992: Dow Corning announced that it would no longer make five implant grades of silicone for sale after March 31, 1993, but that it would continue to manufacture 45 other medical grades of silicone materials.

January 8, 1993: FDA published a 515(b) proposal in the Federal Register calling for safety and effectiveness data for saline-filled implants. The proposal provided for a 60-day comment period.

June 2, 1994: FDA sponsored a Part 15 Hearing on saline breast implants to hear testimony from all interested parties concerning the timing of the agency's review of the safety and effectiveness of saline-filled breast implants. FDA promised to make a decision by the end of the year.

July 15, 1994: FDA granted conditional approval of an IDE pilot study of 50 patients for a breast implant filled with a purified form of soybean oil (Trilucent™ implant).

October 21, 1994: FDA sponsored the workshop Alternatives to Silicone Breast Implants. The workshop provided a forum for FDA to present draft guidance concerning testing requirements for alternative breast implants.

December 23, 1994: FDA issued a Talk Paper describing the types of studies required to demonstrate the safety and effectiveness of saline breast implants and

the date the studies are expected to be completed. Preclinical data were submitted

April 20, 1995: FDA updated the patient information sheet (entitled “Information for Women Considering Saline-Filled Breast Implants”) on the risks of saline-filled breast implants that manufacturers give to physicians who, in turn, provide them to patients considering implant surgery.

January 11, 1996: FDA sent a letter to current and potential manufacturers of silicone gel-filled breast implants detailing the type of information needed for core studies (stage 3 studies) of the silicone gel-filled implants for augmentation, reconstruction, and revision patients.

September 4, 1996: FDA cleared Poly Implants Protheses (PIP) for marketing of saline-filled breast implants through the 510(k) process.

September 19, 1996: FDA received a Citizen's Petition from the Y-Me National Breast Cancer Organization and other related organizations requesting that the FDA ease restrictions on the availability of silicone gel-filled breast implants for women who choose reconstruction after a mastectomy and who have other special medical needs.

February 11, 1997: FDA received a Citizen's Petition from implant recipients (who reported significant problems with their silicone implants) requesting that the FDA revoke permission granted to manufacturers to make silicone gel-filled breast implants available to women with breast cancer and women who previously had implants.

May 20, 1997: FDA cleared Hutchinson International for marketing of saline-filled breast implants through the 510(k) process.

1997: The Department of Health and Human Services (DHHS) asked the Institute

of Medicine (IOM) to conduct an independent, unbiased review of all past and ongoing scientific research regarding the safety of silicone breast implants. A committee of experts in relevant scientific and clinical areas was asked to evaluate past and ongoing studies of the relationship, if any, between implants and systemic disease; assess the biologic and immunologic effects of silicone and other chemical components of breast implants; assess the impact of breast implants, if any, on the offspring of women with implants; and assess the accuracy of mammograms.

Spring 1998: The FDA completed a study to assess the rupture rate of silicone gel filled breast implants.

March 30, 1998: FDA approved McGhan Medical’s Stage 2 (or adjunct study) protocol for silicone gel-filled breast implants for reconstruction and revision only.

May 6, 1998: Mentor Corporation and its subsidiary, Mentor Texas, signed a consent decree of permanent injunction, promising that the company would manufacture its breast implants in compliance with the Quality System Regulation. The Quality System Regulation is critical in helping to assure that medical devicesare consistently high in quality and are safe and effective. FDA permitted Mentor to continue marketing its breast implants because the deficiencies in Mentor’s manufacturing process were not shown to result in a significantly increased risk to women who received this company’s breast implants.

June 5, 1998: FDA approved McGhan Medical's IDE study for silicone gel-filled breast implants for augmentation, reconstruction, and revision for a limited number of patients at a limited number of sites.

November 12, 1998: FDA received a Citizen's Petition from Hyman, Phelps & McNamara requesting that FDA either withdraw the proposed rule calling for PMAs or PDPs for the saline-filled breast implant or reopen the comment period to allow interested persons to address the information that has become available since the publication of the 1993 proposed call for PMAs or PDPs. This petition was denied.

February 1, 1999: FDA cleared Silimed, LLC for marketing of their pre-filled and inflatable saline-filled breast implants through the 510(k) process.

June 22, 1999: The IOM released a comprehensive review of the published literature and ongoing studies on both saline-filled and silicone gel-filled breast implants entitled “Safety of Silicone Breast Implants.” The IOM made a clear distinction between local complications and systemic health concerns. The IOM determined that there was insufficient evidence to establish that either or both types of breast implants cause systemic health effects, such as autoimmune disease, and that there were no new health or safety issues associated with the use of both types of implants. The IOM also concluded that local complications are “the primary safety issue with silicone breast implants.” These local complications include rupture, pain, capsular contracture, disfigurement, and serious infection, which may lead to medical interventions and repeat surgeries.

June 30, 1999: FDA received a Citizen's Petition from Anne Stanswell requesting that FDA ban the use of the silicone gel-filled breast implants. This petition was denied.

October 1999: FDA issued a draft guidance entitled, “Guidance on Preclinical and Clinical Data and Labeling for Breast Prostheses.” This guidance is for saline, silicone gel, and alternative breast implants and is intended to replace FDA’s other guidances for individual types of breast implants