Augmentation mammoplasty with autologous fat grafting

Weigang Cao, Lingling Sheng

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Keywords:Breast augmentation Autologous fat grafting Complications Mammoplasty

ABSTRACT Considering the issues that can accompany prosthetic breast implants, augmentation mammoplasty (AM) with autologous fat grafting(AFG)has attracted growing interest globally,especially in the last two decades,as breast implant-associated anaplastic large cell lymphoma has been increasing in incidence over time.Here, we review the detailed processes of AFG to the breast and the pertinent complications associated with this procedure.This study aims to elucidate the critical points and technique improvements in AM with AFG in recent years,as well as discuss how to decrease complications related to this procedure.Attention was focused on the specific AFG steps,clinical outcomes, and complications to highlight the advantages and disadvantages of the available protocols.

1.Introduction

In 1987, Bircoll1reported the first case of cosmetic breast augmentation using autologous fat and liposuction techniques.However, this report caused a great deal of concerns in the plastic surgery community.In the same year, the American Society of Plastic and Reconstructive Surgeons (ASPRS) Ad-Hoc Committee on New Procedures was unanimous in “deploring the use of autologous fat injection in breast augmentation”, stating that “much of the injected fat will not survive,and the known physiologic response to necrosis of this tissue is scarring and calcification”.These changes were thought to obscure the early diagnosis of breast cancer by mammography and increase the number of breast biopsies for benign conditions.2For the next 20 years, the application and development of techniques in autologous fat grafting(AFG)to the breast were largely hindered in the United States due to this ASPRS position paper.It was not until 2007 that Coleman and Saboeiro3reported 17 patients with breast enlargement who underwent AFG only demonstrated impressive outcomes.This showed that large-volume AFG could be performed safely and effectively in the breast.This report and results of other studies prompted the American Society of Plastic Surgeons Fat Grafting Task Force to publish the following in their 2009 statement:“Fat grafting may be considered for breast augmentation and correction of defects associated with medical conditions and previous breast surgeries; however, results are dependent on technique and surgeon expertise”.4Since then, numerous reports have been published in the literature that have presented a variety of techniques for fat transplantation to the breast, as well as various pertinent complications.5–17This review aimed to elucidate the critical points and technique improvements in augmentation mammoplasty (AM) with AFG in recent years, as well as discuss how to decrease complications related to this type of procedure.Attention was focused on the specific detailed processes for fat graft harvesting, processing, reinjection, recipient site preparation,clinical outcomes,and pertinent complications to highlight the advantages and disadvantages of the available protocols of AFG to the breast.

2.Infiltration

It was not until 1986 that the advent of tumescent anesthesia was introduced by Dr.Jeffrey A.Klein18for liposuction, which makes it possible to obtain large quantities of adipose tissue particles for large-volume fat transfer to the breast.The main ingredients of local anesthetic agents, such as lidocaine and vasoconstrictor epinephrine in wetting solutions, make it possible to perform liposuction under local anesthesia alone without excessive blood loss.As fat grafting to the breasts has attracted increasing interest in the field of plastic surgery,its underlying mechanisms have received considerable attention.Adipose-derived stem cells(ASCs)and stromal vascular fractions(SVFs),which may play an important role in fat graft survival,have been gaining much attention.12,13,17However, Wang et al.19in 2014 demonstrated that lidocaine has a significant impact on ASC survival in lipoaspirates,which could be used for fat grafting.Lidocaine-induced ASC death is dose-dependent and occurs through the mechanism of apoptosis rather than necrosis, and tumescent solutions with dilute lidocaine concentration are superior to local anesthesia with a relatively higher concentration of lidocaine for ASC preservation.Furthermore, the same team verified that completely removing lidocaine from the tumescent solution significantly reduced SVF and ASC apoptosis.20The same group also demonstrated that the acidic standard tumescent solution used in liposuction adversely affects the viability of ASCs isolated from lipoaspirates and that buffering tumescent solution with sodium bicarbonate(SB)can significantly enhance ASC viability.21These results imply the potential improvement of fat grafting by using tumescent solutions without lidocaine or with very dilute lidocaine combined with SB buffering.This may play a role in fat graft survival or improvement of retention,especially in large-volume fat transplantation during AM with AFG.Given the circumstance of fat grafting during breast procedures,removing lidocaine from the tumescent solution for fat harvesting is feasible because the operation is usually performed under general anesthesia.It seems to be the better way of removing tumescent solutions by washing,centrifugation,and cotton pad filtering in order to decrease the impact of lidocaine on fat graft survival before fat transplantation.

3.Fat harvesting

There are two major fat harvesting modalities during large-volume fat transfer to the breast and other body areas.First,with standard lowpressure machine liposuction, the suction pressure varies from-70 cmH2O to -600 mmHg.7,15,17,22The advantages of machine liposuction are its higher effectiveness and efficacy,especially in thin patients with insufficient fat deposits.22Concerns about adipocyte damage from high pressure caused by suction pumps are largely unnecessary if the principles of low negative pressure suctioning during fat harvesting are adhered to.The other fat harvesting method involves syringe liposuction,3,5,6,9,16in which a 10-mL to 60-mL syringe is connected to a single-hole or multiple-hole harvesting cannula.The plunger is gently withdrawn 2–4 cc in volume to maintain a constant low negative pressure.Improper manipulation during syringe liposuction will lead to a negative pressure as high as-718 mmHg if a 60-mL syringe is used.23With respect to harvesting cannulas, most authors prefer to use 2–3-hole blunt tip cannulas 2–4 mm in diameter.3,5–7,15,22Some authors have recently used 12–15-hole cannulas for faster and more efficient harvesting of fat tissues.Great attention must be paid to donor site contour irregularities and morbidities during the use of these multiple-hole cannulas.

4.Fat processing

Fat processing plays an important role in AFG.At present, there are four major methods for fat processing:gravity separation(also referred to as decantation or sedimentation),5,24centrifugation,3,6,9,10,13,15,17,22Telfa cotton rolling (also referred to as cotton pad filtration),1,16,25and CAL.12,13,22Kang et al.24demonstrated that different processing methods could influence the content and function of the SVF in lipoaspirates, as well as graft survival, after transplantation in nude mice.In their experiment, the same volume of 10 mL lipoaspirate suctioned from the same individual was assigned to four groups: decantation (group A),centrifugation (group B), cotton pad (group C), and cell-assisted lipotransfer (CAL; group D).The final volume of purified fats from each group was 7 mL in the decantation group, 5 mL in the centrifugation group,3 mL in the cotton pad group,and 3.5 mL in the CAL group.They found that the SVFs in the decantation group were higher than those in the cotton fad group(4.32±0.75×106/mL versus 1.64±0.84×106/mL,P＜0.05).They also demonstrated that the weight of the fat graft in the decantation group was greater than that in the other three groups(P＜0.05).However,care must be taken to evaluate the experimental results, because the actual volume transplanted in each group was completely different from one another.Briefly, the transplanted fat volumes that correspond to the respective attrition rates in groups A (decantation), B (centrifugation), C (cotton pad), and D (CAL) were 1.4 mL, 1.2 mL, 0.6 mL, and 0.7 mL respectively.Interestingly,Canizares et al.25compared the effect of different processing techniques on fat graft survival and demonstrated that Telfa-processed lipoaspirates had a greater number of functional adipocytes (0.104 U/mL) than centrifuged (0.080 U/mL) and unprocessed lipoaspirates(0.083 U/mL) upon performing a glycerol-3-phosphate dehydrogenase assay (P＜0.05), although they found that centrifugated lipoaspirates had a greater number of progenitor cells per gram of tissue than Telfa-processed and unprocessed lipoaspirates.After 10 weeks of grafting, Telfa-processed lipoaspirates had greater fat graft persistence(70.9% ± 6.2%) than centrifuged (56.7% ± 5.5%) and unprocessed lipoaspirates (42.2% ± 2.7%) (P＜0.05).Telfa-processed lipoaspirates also maintained greater secretions of vascular endothelial growth factor and platelet-derived growth factor-BB at weeks 1 and 2 than centrifuged and unprocessed lipoaspirates.Furthermore, CD31 staining demonstrated an increase in vascular density of the Telfa-processed lipoaspirate at week 2 compared to that of the centrifuged lipoaspirate(37% ± 1% and 14% ± 4% per high-power field;P＜0.05).

Controversy still exists in terms of the effects of centrifugation on the viability of adipocytes and grafts, as well as retention rates after fat transplantation.3,6,7,9,10,15,17,22,26,27Some studies have proposed that higher centrifugal forces lead to damage to adipocytes with lower cell viability,while very low centrifugation forces and simple fat decantation show no detrimental effects on adipocyte viability.10,11,24However,Pulsfort et al.26demonstrated no significant histological alterations in the viability of adipocytes based on different centrifugation speeds from 1 000 rpm to 15 000 rpm, whereas Kang and Luan27recently demonstrated that fat grafts treated with lower-speed centrifugation (800 rpm for 3 min)had more fat necrosis than those treated with sedimentation.

The advantages of centrifugation are not only removal of tumescent fluid, blood cells, debris, oil, and other inflammatory ingredients in the lipoaspirate but also separation of the fat fraction into higher-density and lower-density parts.The higher-density part was shown to have a greater percentage of progenitors, as well as an increased concentration of growth factors.These concentrated lipoaspirates are believed to favor fat survival and have a higher retention rate after grafting.Nevertheless,since there is still concern regarding potential damage to the adipocytes and ASCs from centrifugal forces, it seems more reasonable to apply a lower centrifugal force so as to reduce such damage.

Decantation or sedimentation refers to the process of allowing the lipoaspirate to settle itself by gravitation into its three phases(oil,fat,and aqueous)with time.The bottom aqueous part and the upper part of the oil were drained and discarded,respectively,while the middle part of the fat layer was transferred to syringes for injection.Some commercial devices, such as the Puregraft?system (Cytori Therapeutics Inc., San Diego,CA,USA)and the Revolve?System(LifeCell Corp.,Branchburg,NJ, USA) allow for the collection and gravity separation of lipoaspirate within a sterile closed system.28Approximately 250 mL of lipoaspirate can be harvested and processed within 15 min using the Puregraft?system, while up to 350 mL of lipoaspirate is processed with the Revolve?System in approximately 10 min.29Furthermore, a new P188-based system(Poloxamer wash,adsorption,mesh filtration system,PWAS;AuraGen123 Suction Lipoplasty System,AuraGen Aesthetics LLC,Weston,MA,USA)has recently been developed and has shown promising results in a preclinical study.30The processed tissue from the PWAS had a significantly higher volume fraction of adipose tissue in the “fat” layer(89% ± 3%) than both the RLDS (Revolve Advanced Adipose System,Allergan Corporation, PLC, Madison, NJ, USA) (76% ± 10%;P=0.02)and unprocessed lipoaspirate (37% ± 12%;P＜0.001).A further advantage of PWAS is that it is designed to process a large volume(700 mL)of lipoaspirate in a single harvest,greatly reducing the overall surgical time required,especially in large-volume AM with AFG.30

5.Fat injection

Theoretically,fat grafts can be injected into various levels within the breast, including the retroglandular space, pectoralis major muscle,retropectoral space, subcutaneous tissues, and even the breast parenchyma.There is consensus that fat grafts can be safely injected into the retroglandular space, pectoralis major muscle, retropectoral space, and subcutaneous tissues.The question is whether one site is more effective than the other.Shi et al.31have demonstrated in mice that fat retention was best when injected into fat pads,followed by subcutaneous layer and intramuscular injection.Clinically, Guo et al.32in 2019 evaluated the volume retention rates of different layers in the breast during lipoaugmentation.They found that the volume retention rate was significantly higher (59.00% ± 13.84%) in the periglandular area than in the pectoralis major muscle(47.21%±22.41%;P=0.04).Augmentation was significantly higher(32.13%±12.96%)in the periglandular area than in the pectoralis muscle (4.95% ± 4.23%).They concluded that the periglandular area was a better recipient site than the muscle for transferred fat.It was speculated that the lower fat retention rate in the pectoralis muscle was possibly the result of pectoralis muscle contraction and compression, as well as the constricting effect of the pectoral fascia,which could limit the graft-to-capacity ratio.This hypothesis was recently verified by an experimental study, in which Shi et al.33demonstrated that intramuscularly injected fat grafts with botulinum toxin A (BTX-A) had a better retention rate than fat grafts injected into muscles without BTX-A.However, in their landmark manuscript, Coleman and Saboerio3described the techniques and rationale for placing majority of the fat into the pectoralis major muscle, followed by the retropectoral and prepectoral spaces.The fat was placed into the superficial subcutaneous layer to optimize breast shape.The least amount of fat was placed in the breast parenchyma to increase the projection.However, the exact proportion injected into each plane was not determined by the authors.Illouz5in 2009 stated that fat is woven into the subcutaneous and intragladular spaces of the breast.Li16in 2014 presented his technique for injection of fat tissues into the breast,wherein he stated that the fat is placed in multiplanes from the deep to subcutaneous tissue.Approximately two-thirds of the collected fat was injected into the retroglandular and intraglandular space layer by layer, and the remaining tissue was injected into the subcutaneous space.Whether or not to inject fat directly into the breast parenchyma remains controversial based on the aromatase theory and the possibility that adjacent progenitor cells become activated.9,34Coincidentally, two cases in Coleman’s series were diagnosed with breast cancer on mammography,wherein the lesion in one case was in the fat-grafted area, while in the other case, the cancer occurred in an untreated area.3In 2016, Cheng et al.35reported a case of mucinous carcinoma of the right breast after cosmetic augmentation with autologous fat grafts.To the best of our knowledge, only three cases of breast cancer have been reported in the literature after cosmetic augmentation with fat grafts, with the relationship between breast cancer and fat grafting to the breast parenchyma still needing further elucidation.

6.Recipient site preparation

The outcomes of AFG to the breast are largely technique and surgeon expertise-dependent due to the multiple processes involved,including fat harvesting, processing, reinjection, and recipient site preparation, of which the importance of recipient site preparation to final graft retention is usually overlooked by practitioners.There are two major theories that explain long-term volume retention after fat transplantation.The “cell survival theory”, which was first described by Peer36in 1950, assumes that grafted adipocytes initially survive through diffusion, and then by receiving blood supply from the recipient-site tissue through a process of angiogenesis similar to skin grafting.Another theory, called the “host replacement theory”, which was also described by Peer37and more recently by Doldere et al.38and Eto et al.,39assumes that the transplanted adipocytes will eventually die, and that the dead cells will be replaced by the progenitor or stem cells from the transplanted fat particles or from the recipient host after new angiogenesis completed.

Regardless of which theory is applicable, maximal contact between the adipose tissue grafts and the recipient-site tissue bed, which allows for the establishment of new blood supply as quickly as possible, is a prerequisite for better graft retention after transplantation.Therefore,the volume of the recipient site and its vascularity are critical for its capacity to accommodate the transplanted graft volume.In 2012, Del Vecchio8came up with the concept of“graft-to-capacity ratio”,which is defined as the volume of the graft as it relates to the volume of the recipient site.It is necessary to increase the capacity of the recipient site to prevent its overload;otherwise,overloaded grafts will inevitably lead to fat necrosis,and finally,reduce fat graft volume maintenance.

To overcome the small capacity of some thin patients, Khouri9–11initially invented a breast external expansion device named the Brava system and demonstrated its effectiveness and efficacy in increasing breast volume, as well as promoting neovascularity in the breast.The data demonstrated an expansion volume increase using Brava averaging 200% or a tripling of breast volume.Micromechanical forces on subcutaneous cells cause increased cellular proliferation, increased capillary density, and increased interstitial space.The new program of external volume expansion has been shortened to 3–4 weeks by optimizing the expansion duration and intensity without reducing expansion efficacy.

7.Management of complications

Nevertheless, AM with AFG also has inherent limitations and complications.The most common complications following AFG to the breast are directly related to graft loss and demonstrate a variety of forms of fat necrosis.The resultant scarring and subsequent calcification from fat necrosis have raised safety concerns for difficulties in distinguishing these lesions from breast malignancy.2Wang et al.40in 2011 concluded that autologous fat injection for breast augmentation should continue to be prohibited because clustered microcalcifications can be found after the procedure, which cannot be distinguished from malignancy.This undoubtedly provoked heated debates again, and many authors expressed their opinions of disagreement.40–44Although fat grafting to the breast, similar to other breast surgeries, could potentially interfere with breast cancer detection, no evidence to date has strongly suggested the presence of this interference.In contrast, Yoshimura and Rubin45found fewer mammographic changes in fat-grafted breasts than in the breasts of breast reduction patients.Therefore, it seems more reasonable to develop imaging standards for separating benign from malignant calcifications in fat-grafted breasts,rather than prohibiting fat transfer to the breasts.Moreover, fat necrosis was finally confirmed by biopsies of the lesions in eight patients in Wang’s series (48 cases in total),which may have resulted from their technical points,such as“The interval between stages was 1–3 months.Finally, massage was performed”.40However, even with refined techniques and novel innovations, it seems that fat necrosis can be prevented from occurring completely.3,5,6,9,15,17,22,27,40,45–47

There are a variety of presentations of nonabsorbed necrotic fat,such as an oily cyst, sclerotic induration, and a calcified solid tumor.15,17,47These lumps that develop after fat grafting to the breast can subsequently be classified into four types: cystic, solid, complex, and calcification.47Complications of fat necrosis in the breast may cause physical and psychological discomfort,and should be treated promptly and properly.Lin et al.17demonstrated their experience in managing necrotic fat lumps after cosmetic AM with fat grafting.They found that fat necrosis occurred in 9.6% of cases (66 of 685) that had undergone autologous fat transplantation to the breasts.The average time before the first detection of the breast lump was 108 ± 45 days.The authors’ treatment algorithm includes aspiration for oily cysts and excision of sclerotic nodules or calcified lumps.Oil cysts are usually soft and mobile upon palpation.This type of lump constitutes the majority of fat necrosis.The management of oil cysts is simple,and most can be aspirated by utilizing a 20-cc syringe and an 18-gauge needle.17In contrast to soft oil cysts,the calcified lump appears firm and hard on palpation and can be either mobile or fixed.A small superficial calcified lump can be excised directly through a small 2-to 3-mm stab incision,whereas larger calcified lumps(＞3 cm)might be approached with a larger incision.The incision should be placed in the inframammary fold, periareolar, or transaxillary creases for optimal cosmesis.If the transaxillary approach is used, assistance with endoscopic instruments may be necessary to facilitate excision.In addition,smaller, asymptomatic, and deep-seated (nonpalpable) solid masses found incidentally by imaging may not require any surgical intervention.17Furthermore,a new strategy with a minimally invasive approach recently proposed by Qu et al.47has shown promising results in the surgical management of lumps after AFG to the breast.They successfully excised larger lumps through a smaller 5-mm incision with the assistance of a vacuum-assisted breast biopsy system under preoperative ultrasound guidance.

8.Conclusion

AM with AFG appears to be safe and effective with relatively low acceptable complication rates when adhering to the principles and concepts described here.In general,manipulations favoring fat graft survival or improving retention rate after transfer to the breast include, but are not limited to, reduced damage to adipocytes and SVFs; preservation of viable and functional adipocytes, SVFs, and growth factors, while removing the detrimental contents in lipoaspirates; even and proper distribution of fat grafts;and maximizing contact between the grafted fat and the recipient site.Good success rates have been observed in the setting of properly controlled protocols focusing on detailed processes of fat grafting, including fat harvesting, processing, reinjection, and recipient site preparation.However, it is difficult to determine the optimal method to be implemented because many factors may affect the final results of fat grafting to the breast.There is still a lack of standardization across all steps of fat grafting to the breast procedure, which makes comparison difficult and imprecise.Further randomized prospective clinical studies are needed to determine the optimal protocol for cosmetic augmentation using autologous fat grafts in the breast.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Authors’contributions

Cao W:Conceptualization,Writing-Original draft preparation.Sheng L: Writing-Reviewing and Editing.

Acknowledgments

This work was supported by the Shanghai Municipal Key Clinical Specialty Project(grant no.Shslczdzk00901).