Recent advances in volume retention and evaluation methods of fat grafting for breast reconstruction

Fat injections are now one of the most important treatment modalities for breast reconstructive surgeons. Historically, fat injections were not an immediately accepted technique. As early as 1912, fat injection is reported as a treatment for facial atrophy. In the early 1980s, liposuction was used to harvest adipose tissue for fat grafting. However, in 1987, the American Society of Plastic and Reconstructive Surgeons published their opinion that fat injections for breast augmentation are inappropriate because of the poor retention of injected fat tissue and the possibility of calcification, which may make it difficult to detect early-stage breast cancer (1,2).

However, in the 2000s, it became clear that careful manipulation of adipose tissue during fat harvesting and injection could solve the problems reported in the past regarding fat injection. In 2006, Coleman reported that the long-term retention of fat grafting to the face for post-acne scarring, post-tumor resection defects, and rejuvenation was demonstrated (1), and the usefulness of the effects of fat injections for breast deformity was also reported (3). In addition, the American Society of Plastic Surgeons removed the ban on fat grafting for breast reconstruction in 2009. Still, they recommended its cautious use for breast augmentation due to a lack of scientific research and concerns about safety and efficacy (2). Furthermore, various biological effects of adipocytes on breast cancer have been suggested. However, in recent years, oncological safety of autologous fat grafting for breast cancer has also been reported in large, multicentre studies (4). And then, Reconstructive surgeons once again found that fat grafting was a useful therapeutic tool for breast reconstruction. In addition, Khouri et al. found that, as the injected fat volume increases, interstitial fluid pressure in the tissue increases and capillary blood flow is impeded resulting in insufficient oxygen supply to the injected fat, causing necrosis, which prevents improved engraftment of large amounts of fat injection. To address this problem, he reported that the use of an external expander called Brava pre-expands the transplant recipient tissue and promotes angiogenesis, thereby improving tissue compliance and allowing megavolume fat transfer into the breast (2). However, difficulties with ongoing use and skin disorders have been noted with Brava. Alternatives to Brava have also been reported, such as using internal expanders to pre-dilate the recipient tissue and perform fat injections (5). In addition, to enhance graft survival, the effects of cell therapies have been studied, including those that combine fat grafts with the stromal vascular fraction (SVF) (6) and those that combine with some growth factors such as erythropoietin, insulin, interleukin (IL)-8, and platelet-rich plasma (PRP) (7-10).

Although there have been various advanced reports on improving the environment of the recipient tissue and nutrition of the transplanted adipose tissue, it is believed that basic operations such as fat harvesting, purification methods, and injection techniques play an equally important role in the rate of fat cell viability. In terms of suctioning methods, some papers have reported no differences in histological fat cell damage between suction-assisted lipectomy or ultrasonic liposuction, but others have reported better adipose cell survival rates with manual syringe suction (11). In any case, there is a commonality in that it is preferable to use a relatively large suction cannula and to suction at lower pressure in a gentle manner (11). In addition, how the fat is injected is also important, and the three-zone theory is widely accepted as the mechanism of adipocyte engraftment (12). According to the three-zone theory, the most superficial zone is “the surviving zone”, which is less than 300 µm of the edge of the transferred fat tissue. Both adipocytes and adipose-derived stem cells can survive in this zone. In “the regenerating zone”, which varies with the microenvironmental conditions, including the surrounding tissue’s vascularity and attachment, adipocytes die, but adipose-derived stem cells can survive, proliferate, and differentiate into adipocytes. In “the necrotic zone”, which is the most central zone of the transferred tissue, the adipocytes are said to become necrotic. Therefore, the transplanted adipocytes should be injected diffusely as much as possible. Moreover, contaminants such as oil and blood cells may cause local inflammation and promote the degradation of fat cells, so various fat cell-purifying methods have been tried to remove these contaminants. Hoareau et al. reported that, in a mouse model, soft centrifugation (400 g/L min) resulted in less adipocyte death than strong centrifugation (900 g/3 min). Furthermore, the inflammatory cytokines IL-6 and MCP-1, which may be detrimental to adipocyte survival, were lower at 24 hours in soft centrifugation (400 g/L min), suggesting that soft centrifugation may be a better approach (13). He et al. also reported that the soft centrifugation method at 400 g for 1 minute and the cotton pad filtration method showed less cell structural destruction and survival than centrifugation at 1,200 g × 3 min (14). These reports suggested that the optimal centrifugation strength is considered to remove contaminants such as oil and blood cells and not damage adipocytes. Various methods of fat purification other than centrifugation are now being incorporated. Active closed wash and filtration (ACWF), which is defined the immediate collection of lipoaspirate into the device, repeated sterile rinses, and direct extraction of debris and tumescent fluid using an internal filter basket with 200-µm pores under vacuum suction, has recently been reported as a method for fat processing. Vernice et al. conducted a systematic review comparing fat processing using ACWF with other fat processing techniques in 2023, such as centrifugation, telfa rolling, and passive filtration (15). Gabriel et al. conducted a comparison between ACWF and centrifugation, revealing that ACWF could accommodate a greater volume of fat and decrease surgical time (16). Chiu et al. also found the decantation harvest group may be a risk factor for fat necrosis and that the average graft volume was lower in the decantation group than in the ACWF group (50.6 vs. 105.0 mL, P<0.01) (17). Hanson et al. also report that ACWF significantly increased the rate of adipose tissue preparation compared to passive filtration (19.8 vs. 5.3 mL/min, P≤0.001) (18). Ruan et al. demonstrated that autologous fat transfer via centrifugation had a higher complication rate than Telfa rolling and ACWF (19). Valmadrid et al. noted that ACWF was independently related to lower rates of imaging-confirmed fat necrosis compared to Telfa rolling without an increase in other complications (20). Assad also stated that the overall grafting complication rate is comparable regardless of the processing technique (21). These studies demonstrate that ACWF can purify more fat in less time than other methods and has fewer complications, such as fat necrosis. A more recent report on the efficacy of ACWF indicates that Chen et al. conducted a randomized controlled trial (RCT) involving fat purification techniques in 58 patients undergoing fat grafting (Table 1) (22). They evaluated the effect of fat grafting in 26 of 58 patients by three-dimensional (3D) scanning before and 3 months after surgery, comparing three groups: ACWF (n=9); low-pressure decantation technique (n=6); and standard decantation (n=11). ACWF and the low-pressure decantation technique showed higher volume retention rates than standard decantation as assessed by 3D scanning at 3 months postoperatively (P<0.05). This research is significant because, in contrast to many other papers that were case-control studies or case reports, it compared three groups of fat preparation methods in an RCT to evaluate the results of fat injection grafting procedures. It is also useful to note that they attempted to assess objectively the volume retention of fat injections with 3D images rather than subjectively with two-dimensional photographs. There have been other reports on the evaluation of breast volume using 3D imaging. O’Connell et al. performed volumetric evaluations of breasts with 3D images, and they examined the accuracy of the assessment in detail (23). The intra-observer variation over ten repeat evaluations of the patient’s breasts demonstrated mean coefficients of variation of 3.9% for one observer and 3.8% for the other observer, which is much larger than the intra-observer variation (0.58%, 0.49%) previously obtained using a phantom, pointing to the difficulty of measuring the human breast. Wang et al. also mentioned that the accuracy of breast volume measurement with a 3D scanner is limited by the inability to define the chest wall side in the systematic review (24). In addition, they describe the advantages and disadvantages of evaluation methods other than 3D imaging, such as magnetic resonance imaging (MRI) and water displacement methods. The water displacement method is currently regarded as the volumetric gold standard, but patient compliance varies, and its reproducibility and accuracy are poor. MRI is less invasive than 3D computed tomography (CT) in terms of radiation exposure, however, breast volume may be impacted by the MRI scanner coils’ fixed shape and size, particularly for larger breasts.

In addition to volumetric evaluation of the reconstructed breast using 3D images, methods of evaluating the morphology of the reconstructed breast have also been reported. O’Connell et al. used root mean square (RMS) projection, which is calculated from the distances at the corresponding x–y coordinate points between the two breasts. They examined the accuracy of the evaluations in detail. The mean difference between observers was 0.43 mm for average symmetry values that ranged from roughly 3.5 to 15.5 mm (23). We also calculated the RMS from the breast contour curve and further developed a score called the breast contour score using the RMS as a variable, and we reported a method to express the morphological difference between the left and right breasts as a relative value from 0 to 100 (25). However, in terms of accuracy and reproducibility, none of the methods that have been reported are sufficient for evaluating reconstructed breasts.

Although the techniques of fat grafting and evaluation methods are developing rapidly, and the efficacy of fat grafting in breast reconstruction is already recognized as a useful method for reconstructive surgeons, larger-scale RCT studies are needed to definitively prove it, and the development of minimally invasive, accurate, and reproducible breast volume and morphology evaluation methods is essential.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

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