Discussion (2011)

Sir:FigureI read with interest the discussion by Dr. Nahabedian regarding our article, “Macrolane for Breast Enhancement: 12 Month Follow-Up.”1,2 In his discussion, Dr. Nahabedian acknowledged the study as being well designed, and accurately summarized the results. However, Dr. Nahabedian questioned the lack of clinical studies performed for this product. Further studies, including long-term follow-up of patients, are indeed necessary. Our current study1 has now been followed for 2 years and an additional 6 years of follow-up is planned; to-date, no unexpected safety concerns have arisen. Additional ongoing trials include a prospective study in 71 women with 2-years' follow-up, and a retrospective study in 93 women; both of these include a retreatment cohort. The first study of 19 patients was published in Aesthetic Plastic Surgery in 2009.3 In another recent study by Inglefield,4 194 women received injections of Macrolane (Q-Med, Uppsala, Sweden) in the breast and were followed-up for a mean of 13.3 months. No unexpected safety concerns arose after treatment. In addition, a prospective registry of women who receive Macrolane injections in the breast that cross-checks against women on a breast cancer registry has been initiated in Sweden. Macrolane is intended mainly for reshaping and smaller augmentation of the breast than is typically undertaken with silicone implants. Consequently, glandular atrophy associated with long-term implantation of oversized silicone implants is unlikely to occur. The nonpermanent nature of Macrolane also allows for retreatment to be customized as the body changes. This may lead to a more natural appearance over time than with permanent fillers or surgery, and any gel dislocation can be easily removed with aspiration or by injection of hyaluronidase. In my experience, I have observed no changes in the contour of the breast in women who have had complete degradation of the gel. In the study by Inglefield, 19 percent of patients were highly satisfied with the results and requested repeated injection.4 In my own patients treated outside of clinical studies, approximately one-third have requested retreatment and one-third have chosen to convert to permanent implants. Macrolane treatment therefore helped these latter patients to overcome their previous reluctance to undergo surgery. These observations are equivalent to the so-called 747 effect, as noted by the American Society of Plastic Surgeons in their market research, where trust in minimally invasive procedures increases the patients' willingness to have a nonplastic surgeon perform an aesthetic surgical procedure from 7 percent to 47 percent. Dr. Nahabedian questioned the diffusion of the product and the potential for harmful effects. No major displacement of the product into the glandular tissue has been observed in studies so far. Moreover, Macrolane consists of 98 percent water and 2 percent crosslinked hyaluronic acid (20 mg/ml). The hyaluronic acid is believed to degrade slowly, by means of the same mechanisms as endogenous hyaluronic acid, and degraded Macrolane likely exits the breasts through the lymphatic system, rather than by diffusing into the glandular tissue. With an injection volume of 125 ml, only 6.8 mg of hyaluronic acid is released into the breast per day over 12 months, equating to a concentration of 0.068 mg/ml in a small 100-ml breast with no lymphatic drainage. For comparison, the concentration of hyaluronic acid in the interstitial fluid of tissues is considered to be in the milligram-per-milliliter range,5 and an estimated 5000 mg of hyaluronic acid is cleared by the average human per day. It should also be remembered that more than 11 million facial injections of nonanimal stabilized hyaluronic acid gel (Restylane products; Medicis Aesthetics, Inc., Scottsdale, Ariz.) have been administered with a very low frequency (<0.06 percent) of relatively mild adverse advents (Q-Med AB data on file). Dr. Nahabedian also raised questions about the implications of Macrolane injections for breast imaging. Recently, a group of expert radiologists examined mammograms from women following Macrolane injection and agreed that, as with breasts that have undergone fat injection, reshaping, or oncoplasty, mammography plus additional ultrasonography is sufficient to permit evaluation of the breast tissue.6 Consequently, because of potential screening issues, Macrolane injections are not recommended for women with an increased risk of breast cancer or substantial breast scarring. A 7-year follow-up imaging study of six women showed no significant negative effects on the breast parenchyma (Q-Med AB, data on file). Ongoing prospective clinical trials are listed on ClinicalTrials.gov and are starting to be published in English language PubMed-indexed journals, which will begin to adequately inform the medical community of the validity of data on this product. Per Hedén, Ph.D. Plastic Surgery, Akademikliniken, Storängsvägen 10, Stockholm 11542, Sweden, [email protected] ACKNOWLEDGMENT Editorial assistance was provided by Dr. Elizabeth Hutchinson on behalf of Fishawack Communications, supported by Q-Med AB, Uppsala, Sweden.