Autologous Fat Grafting for Cosmetic Breast Augmentation: A Systematic Review

Transcription

1 Breast Surgery Review Article Autologous Fat Grafting for Cosmetic Breast Augmentation: A Systematic Review Aesthetic Surgery Journal 2015, Vol 35(4) The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com DOI: /asj/sjv030 Marie Voglimacci, MD; Ignacio Garrido, MD, PhD; Ali Mojallal, MD, PhD; Charlotte Vaysse, MD, PhD; Nicolas Bertheuil, MD; Audrey Michot, MD; Jean Pierre Chavoin, MD; Jean Louis Grolleau, MD; and Benoit Chaput, MD Abstract Background: Breast augmentation is one of the most popular aesthetic surgical procedures. The only potential alternative is autologous fat grafting (AFG), which is not new in principle. This procedure has been used on native breasts since 2009, following the recommendations of some learned societies. Objectives: We performed a systematic review to determine the current worldwide status of fat grafting for aesthetic breast augmentation. Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria was conducted using the PubMed, EmBASE, and Cochrane library databases. This protocol was registered at the National Institute for Health Research, Prospective Register of Systematic Reviews. Results: A total of 42 articles published between 1987 and July 2014 were included. Most of the studies had a low level of evidence, with only one level 2 study, published by Spear (2014), a prospective cohort study which included 10 patients. The publications were from North America, Europe, and Asia. The indications were aesthetic augmentation (92.4%) and congenital malformation (7.6%). Two cases of cancer were reported among the 2023 patients included (0.09%), with a mean follow-up of 22 months, although the follow-up was insufficient for medium- and long-term cancer diagnoses. Conclusions: AFG seems to be a major tool in this field, but we must remain cautious about its systematization for this indication. Preoperative patient selection is essential but underreported. AFG appears particularly relevant in breast malformations. We believe that this method should be practiced within the scope of a national or international registry with proper follow-up of patients. Level of Evidence: 3 Accepted for publication February 3, Therapeutic Drs Voglimacci and Chaput are Staff Surgeons and Drs Garrido, Grolleau, and Chavoin are Professors in the Department of Plastic, Reconstructive, Burns, and Aesthetic Surgery at the University of Toulouse Rangueil, France. Dr Mojallal is a Professor in the Department of Plastic, Aesthetic, and Reconstructive Surgery at Edouard Herriot Hospital, University of Lyon, France. Dr Vaysse is a Staff Surgeon in the Department of Surgery and Gynecology and a member of the Faculty of Medicine at the University of Toulouse Rangueil, France. Dr Bertheuil is a Staff Surgeon in the Department of Plastic, Reconstructive, and Aesthetic Surgery at the Hospital Sud, University of Rennes 1, France. Dr Michot is a Staff Surgeon in the Department of Surgical Oncology at the Institut Bergonié and a member of the Faculty of Medicine at the University of Bordeaux Segalen, France. Corresponding Author: Dr Benoit Chaput, Department of Plastic, Reconstructive, Burns, and Aesthetic Surgery, CHU Rangueil, 1, Avenue Jean Poulhès, Toulouse, France. benoitchaput31@gmail.com

2 Voglimacci et al 379 Breast augmentation is one of the most frequently performed cosmetic surgical procedures, according to statistics released in 2013 by the International Society of Aesthetic Plastic Surgery 1 and the American Society for Aesthetic Plastic Surgery. 2 The only alternative is autologous fat grafting (AFG), or lipofilling, which is not new. In 1893, Neuber first described filling retractile scars with fat, 3 followed by Czerny, 4 who reported a back lipoma transfer for breast reconstruction in The procedure continued to develop during the 1950s, but its use in breasts was forbidden by the American Society of Plastic Surgeons (ASPS) in because of issues related to efficacy and safety. Nevertheless, there is increasing interest in lipofilling for other indications. 6,7 The ASPS Fat Graft Task Force was created in Its objective was to assess the efficacy and safety of lipofilling in breast surgery and establish evidence-based recommendations in order to promote its use. Many articles have been published, and have brought about a change in the position of the learned societies: AFG was not contraindicated for native breasts, but was regulated in the USA in 2009, following the ASPS Fat Graft Task Force report, 8 and in France in Figure 1 shows the growing interest in this procedure. Some teams remain reluctant to perform this procedure, claiming a lack of reliability and efficacy with respect to the volume, radiological impact, and interference with breast cancer screening, as well as an uncertain oncological outcome. In this context, we conducted a literature review to determine the worldwide status of fat grafting for aesthetic breast augmentation in METHODS Study Design A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria. The protocol followed the a measurement tool to assess systematic review (AMSTAR) criterion, was registered at the National Institute of Health Research, and was published on the Prospective Register of Systematic Reviews website. 14 PubMed, EmBASE, and Cochrane Library searches were performed in July 2014 using the following terms: fat grafting, fat transplantation, fat injection, lipofilling, lipotransfer, lipomodeling, lipostructuring, and breast. Selection Criteria We included all original articles concerning patients who had undergone AFG on native healthy breasts that were Figure 1. Publications concerning autologous fat grafting in healthy breasts by year.

3 380 Aesthetic Surgery Journal 35(4) published between January 1987 and July Reviews and studies on breast reconstruction after cancer were excluded. Data Collection The full text of each article was read critically by two independent surgeons (B.C. and M.V.) to obtain precise information on the study data, including authors, publication date, study location, type of study, evidence level, number of patients, indication(s), perioperative management, surgical procedures, efficacy, complications, and radiological and oncological impact. We included only articles providing average follow-up figures, and we indexed the study patient numbers to assess the global average follow-up. Finally, we studied the explicit application (or lack) of the main recommendations of American, French, and British learned societies, including patient information, current state of scientific knowledge on lipofilling, exclusion of patients at risk of breast cancer (aged 35 years, family history, breast cancer (BRCA) susceptibility gene mutation), and preoperative imaging. These recommendations were published by the ASPS in 2009, 8 bythesociétéfrançaisedechirurgie Plastique Reconstructrice et Esthétique (SoFCPRE) in 2011, 9 and by the British Association of Aesthetic Plastic Surgeons (BAAPS) in We also included the explicit agreements of the Institutional Review Boards (IRBs) and Ethics Committees, where present. RESULTS Among the 860 articles initially identified by the search, 42 were selected. They were published between January 1987 and July 2014, with 2023 patients included in total (Figure 2). Most of these studies had a low evidence level (Table 1) The only study with level 2 evidence was a prospective cohort study of 10 patients followed-up for 12 months, published by Spear in The publications were essentially North American, European, and Asian (Table 2). Most of the studies were published after Indications, Procedures, and Perioperative Management Indications The operative indications were primary or secondary aesthetic breast augmentation for 92.4% of patients (n = 1870) and congenital malformations (Poland syndrome, tuberous breasts) for 7.6% (n = 153 patients, seven specific studies). Perioperative Management Table 3 shows the implementation of the recommendations by the authors of the studies (n = 20). Six studies reported an ethics committee or IRB agreement. Surgery was practiced under general anesthesia in most cases. No recommendations were provided concerning antibiotic prophylaxis: five studies used antibiotics but their use was not specified in the others. Pre-expansion with a BRAVA device was used in five studies and included 764 patients. The main objective was to improve the surfaces that interfere with AFG, helping their neovascularization by preexpanding the receiving tissues. In a study of 81 patients, Khouri et al 50 reported a survival rate for grafted fat tissue that was higher than those reported in procedures without pre-expansion (82 ± 18% vs. 55% ± 18%; p <.01). More recently, the same authors proposed the megavolume fat transfer theory by means of BRAVA, 52 reporting an AFG survival rate of 76.9%. Procedure: Fat Harvesting No preferred donor site was provided in the studies; fat can be harvested from the abdomen, hips, thighs, or buttocks, depending on patient morphology. The fat-harvesting techniques were essentially the same in all studies and followed the non-traumatic harvesting method of Coleman, using a small-diameter cannula and a low-pressure aspiration system (Table 4). 6,7 Technique: Fat Processing The fat tissue was almost always processed by centrifugation, and pure fat tissue was harvested, corresponding to the intermediate portion. Five studies, 27,36,40,54 with a total of 123 patients, reported techniques for stem cell autoenrichment. Four of these were published by Japanese authors and promote the principle of cell-assisted-lipotransfer, where the stromal vascular fraction is isolated from the first half of the harvested tissue and added to the second half. The fifth article was a Slovenian publication that reported a case of auto-enrichment with bone marrow derived mononuclear cells harvested from the iliac crest. No major differences in results were observed when these five studies were compared to those utilizing more usual techniques: fat resorption rates were 40 60% and volume gains were a maximum of 200 ml/breast. Technique: Fat Reinjection The injections were made using small syringes (3 20 ml) and a small-diameter cannula following the micro-tunnel technique, with the material released as a multilayer trellis. Most authors recommend avoiding the mammary gland and describe injecting into the subcutaneous, retro-glandular, or pre- and retro-muscular spaces, but there was no official recommendation. In our opinion, the absolute avoidance of glandular injection seemed illusory. Postoperative Management and Follow-up Patients underwent one to five sessions (Table 4). In some studies, the patients were required to wear a contention bra for

4 Voglimacci et al 381 Figure 2. Flow chart of articles research and inclusion criteria. 1 month. The postoperative follow-up was up to 1 year, with scheduled clinical and radiological controls. The overall follow-up was from 6 months to 13 years (mean = 22 months). Efficacy, Complications, Radiological Impact, and Oncological Risk Volume Gain and Patient Satisfaction The volume gain assessment was described in 17 articles with 1106 patients. Objective measurements were collected by three-dimensional magnetic resonance imaging (MRI) reconstruction in 14 studies (885 patients), ultrasonographic measurements in 1 study (33 patients), interferometry tri-dimensional measurements in 1 study (136 patients), and clinically simple measurements in 1 study (52 patients). Table 5 shows the assessment modalities and results. The patients were satisfied in most cases, but many studies had no objective method of assessing satisfaction (such as a validated questionnaire or quality-of-life scale). Complications A total of 256 complications were found (12.6% of procedures). Thirty-seven were reported as case reports or series, but the adverse events and initial surgery were not provided in sufficient detail. We did not have precise data on the technical aspects of the surgery or the perioperative management of these patients. There were 60 cases (<3%) of cytosteatonecrotic lesions, 1 case of pneumothorax, and 18 cases of infection (including 3 patients with sepsis who were admitted to the intensive care unit). Sixteen patients required a further surgical procedure following the complications.

5 382 Aesthetic Surgery Journal 35(4) Table 1. General Presentation of Included Articles, Sorted by Evidence Level Article Study Location Study Design Evidence Level (Provided by Origin Journal) Number of Included Patients Mean Age (Range When Mean not Reported) Bircoll and Novack, USA Case report Bircoll, USA Case report 5 1 NR Hörl et al, Germany Case report 5 1 NR Maillard, Switzerland Case report Castello et al, Spain Case report Valdatta et al, Italy Case report Kwak, South Korea Case report Pulagam et al, USA Case report Wang et al, China Case series Carjaval and Patiño Colombia Case series Pinsolle et al, France Case series Yosshimura et al, Japan Case series Mu et al, China Case series Lazzaretti et al, Italy Case report 5 1 NR Yoshimura et al, Japan Case series Lee et al, South Korea Case report Delay et al, France Case report Talbot et al, USA Case report Wang et al, China Case series Kim et al, South Korea Case report Yang and Lee, South Korea Case report Kamakura and Ito, Japan Prospective cohort Del Vecchio, USA Case report La Marca et al, France Case series Auclair et al, France, USA Case series NR Bulgin et al, Slovenia Case report Matsudo and Toledo, Brazil Case series 4 21 NR Coleman and Saboeiro, USA Retrospective cohort Zheng et al, China Case series 4 66 NR Zocchi and Zuliani, Italy Retrospective cohort Hyakusoku et al, Japan Case series Delay et al, France Case series NR (Continued )

6 Voglimacci et al 383 Table 1. (Continued) Article Study Location Study Design Evidence Level (Provided by Origin Journal) Number of Included Patients Mean Age (Range When Mean not Reported) Illouz and Sterodimas, France Case series Herold et al, Germany Prospective cohort 4 10 NR Ueberreiter et al, Germany Prospective cohort 4 52 NR Del Vecchio and Bucky, USA Prospective cohort Khouri et al, USA, Germany, GB Prospective cohort Fiaschetti et al, Italy Prospective cohort Khouri et al, USA, Italy Case series Veber et al, France Retrospective cohort Rubin et al, Japan (fat grafting), USA (breast reduction) Controlled retrospective cohort, no randomization Spear and Pittman, USA Prospective cohort NR, not reported. Table 2. Geographical Distribution of Publications Country of Origin Number of Articles Number of Patients USA France Japan Table 3. Explicit Application of Recommendations of Learned Societies in Articles Published Since 2010 Exclusion of breast cancer high-risk patients (BRCA mutation, family or personal history) Yes No NR 1 (5%) 0 19 (95%) China Italy South Korea 4 4 Germany 3 63 Brazil 1 21 Colombia 1 20 Spain 1 1 Switzerland 1 1 Slovenia 1 1 Exclusive inclusion of patients aged <35 Preoperative general information on procedure Specific information on lack of high-level scientific evidence of efficacy and safety Preoperative radiologic control examination Postoperative mammographic control examination at 1 year 5 (25%) 13 (65%) 2 (10%) 5 (25%) 0 15 (75%) (100%) 12 (60%) 3 (15%) 5 (25%) 10 (50%) 5 (25%) 5 (25%) Imaging Nineteen articles conducted preoperative imaging (mammography, ultrasonography, and MRI) in 1195 patients (ie, >50%). Follow-up modalities varied, but almost all of the more recent publications reported a control radiological examination 1 year postoperatively. More than 50% of the authors reported postoperative radiological changes or abnormalities in 1531 (75.7%) patients. These changes were usually benign calcifications or liponecrotic cysts evoking cytosteatonecrosis scars. NR, not reported. Number of published articles since 01/01/2010, n = 20. Five articles (527 patients) described mammographic assessments following the American College of Radiology (ACR) criteria, and >80% of the exams occurred 1 or 2 years after surgery. Most mammographies classified as ACR 3 were re-classified as ACR 1 or 2 after the control examination 6 months later. Ten articles exclusively studied radiological assessments of the procedure, including 201 patients followed for 6 24 months; none showed any interference with breast cancer screening.

7 Table 4. Details on Fat Grafting Technique Article Donor Site Fat Harvesting Fat Processing Injection Injection Sites Injected Volume (ml) Bircoll and Novack, NR NR Addition of insulin: cc for 100 cc of fat tissue 16G Canula, small syringe Number of Sessions Antibioprophylaxy Subcutaneous Yes Bircoll, NR NR NR NR NR NR NR NR Matsudo and NR NR NR NR NR NR NR NR Toledo, Hörl et al, NR NR NR NR NR NR NR NR Maillard, NR NR NR NR NR NR 1 NR Castello, et al Abdomen, trochanters NR NR NR NR NR 1 NR Valdatta et al, NR NR NR NR NR NR 1 NR Kwak, Hips NR NR NR NR NR 1 NR Pulagam et al, Hips NR NR NR NR NR 1 NR Coleman and Saboeiro, Zheng et al, NR Abdomen, hips, trochanters 10 cc syringe, Coleman canula 3 mm canula, vacuum Centrifugation 3 cc syringe Intra-, retro-, and pre- muscular; subcutaneous; ±intra glandular Saline solution cleaning, centrifugation 600 rpm 2 minutes Wang et al, Abdomen NR Centrifugation at ambient gravity 5 cc syringe, 3 mm canula Subcutaneous; retro glandular Carjaval and Patiño, NR NR NR NR Retro muscular; retro and intra glandular Pinsolle et al, Abdomen, trochanters Zocchi and Zuliani, Trochanter, gluteal 2 mm canula, cc syringe 278.6/breast/ session 1to3 NR to 2 NR NR Retro glandular 50/breast/session 1 to 5 NR NR Syringe Centrifugation 1.5 mm canula NR 96/session 1 to 5 NR Saline solution washing, stratification by vibration then decanting 60 cc syringe, 2 mm canula Subcutaneous; retro glandular Associated Techniques 375/breast 1 NR BRAVA (Continued ) 384 Aesthetic Surgery Journal 35(4)

8 Table 4. (Continued) Article Donor Site Fat Harvesting Fat Processing Injection Injection Sites Injected Volume (ml) Number of Sessions Antibioprophylaxy Hyakusoku et al, NR NR NR NR NR NR NR NR Yoshimura et al, NR 2.5 mm canula, classic lipoaspiration Cell Assisted Lipotransfer. Fat divided into 2 equal parts: first used to isolate vascular stromal fraction, second centrifugated, then two parts mixed. 17G canula, cc syringe Peri glandular; subcutaneous; intra muscular Associated Techniques NR Stem cells autoenrichment Mu et al, NR NR NR NR NR /breast NR NR Delay et al, Abdomen, hips Specific canula, no infiltration Illouz and Sterodimas, Abdomen, hips, flanks, knees 60 cc syringe, 4 mm canula Centrifugation 3200 rpm 3 min 2 mm canula, 10 cc syringe, injection of 140 cc for an expected grafting of 100 cc Decantation 10 cc syringe, 2.5 mm canula NR NR NR Non Subcutaneous; intra glandular 145/breast/session 1 to 5 NR Lazzaretti et al, NR NR NR NR NR NR NR NR Yoshimura et al, NR 2.5 mm canula, classic lipoaspiration Herold et al, NR BEAULI : water-jet assisted lipoaspiration, Bodyjet device Lee et al, Hips Lipokit, after tumescent solution injection Cell Assisted Lipotransfer. Fat divided into 2 equal parts: first used to isolate vascular stromal fraction, second centrifugated, then two parts mixed. 17G canula, cc syringe Plane formed between skin and periprosthetic capsula 268/259 1 NR Stem cells autoenrichment Separation of fat and NR NR NR BEAULI : water water : Lipocollector jet assisted Lipokit, centrifugation 4500 rpm 3 min Injection canula Intra and pre muscular; retro glandular; subcutaneous Yes (Continued ) Voglimacci et al 385

9 Table 4. (Continued) Article Donor Site Fat Harvesting Fat Processing Injection Injection Sites Injected Volume (ml) Delay et al, Abdomen, hips, buttocks Manual lipoaspiration 3 mm canula Centrifugation 3000 rpm 3 min 10 cc syringe, 17G canula NR Volume per session : 127/209/82/206/ 185 Number of Sessions Antibioprophylaxy 5 NR Talbot et al, Abdomen NR NR NR NR NR 1 Oui Ueberreiter et al, NR BEAULI : water-jet assisted lipoaspiration, Bodyjet device Wang et al, NR Manual lipoaspiration 20 cc syringe Associated Techniques Separation of fat and NR NR 184 ( ) 1 to 2 NR BEAULI : water water : Lipocollector jet assisted Sedimentation NR Retro glandular to 4 NR Kim et al, Abdomen NR NR NR NR NR 2 NR Yang and Lee, NR Lipokit, after tumescent solution injection Squeeze centrifugation NR NR 212 to 295/session 4 Oui Veber et al, NR Coleman NR NR Retro muscular and subcutaneous Kamakura and Ito, Abdomen, hips 3 mm canula after infiltration Fat tissue divided into 2 equal parts: first used to isolate stem cells (Celution 800 System + enzymatic protéolytic agent), then added to second part and processed with Celution 800 System Del Vecchio and NR NR Low force Bucky, centrifugation Rubin and Yoshimura, NR 2.5 mm canula Cell Assisted Lipotransfer. Fat divided into 2 equal parts: first used to isolate vascular stromal fraction, second centrifugated, then two parts mixed. Seringue Cellbrush and multilayer injection Retro and intra muscular; subcutaneous; retro glandular to 3 NR and Yes Stem cells autoenrichment NR NR NR BRAVA Reinjection in small aliquots Intra muscular; subcutaneous (374 to 678) NR NR (Continued ) 386 Aesthetic Surgery Journal 35(4)

10 Table 4. (Continued) Article Donor Site Fat Harvesting Fat Processing Injection Injection Sites Injected Volume (ml) Del Vecchio, Abdomen, hips 3.5 mm canula, after infiltration Khouri et al, NR 2.7 mm canula, aspiration syringe 300 mmhg, closed system La Marca et al, Abdomen, gluteal, thighs 3 mm canula, syringe with minimal depression Auclair et al, NR 3 mm canula, classic lipoaspiration 500 mmhg Fiaschetti et al, NR Specific canula Coleman Kit after infiltration Bulgin et al, Abdomen, hips, flanks Manual lipoaspiration after PureGraft infiltration Spear and Pittman, Abdomen, hips 3 mm canula, classic lipoaspiration 500 mmhg Khouri et al, NR 2.7 mm canula, aspiration syringe 300 mmhg, closed system NR, not reported. Centrifugation at ambient gravity then centrifugation at 300 to 450 rpm 2 min Centrifugation 15 g 3 minutes Centrifugation 3000 rpm 4 min Centrifugation 3000 rpm 2 min Centrifugation 3000 rpm 4 min, combined with platelet-enriched plasma PureGraft device Centrifugation 3000 rpm 3 min Centrifugation 15 g 3 min 14G canula and 60 cc syringe Injection canula 2.4 mm, 1 needle Canule 17G or Coleman 10 cc syringe, 1.5 mm canula Microcanule Coleman Kit 10 cc syringe, Cellbrush canula Number of Sessions Antibioprophylaxy Associated Techniques Subcutaneous 600/breast 1 NR BRAVA Retro and intra muscular; subcutaneous; retro glandular 282 (90-600) 1 NR BRAVA multilayer 255/session 1 to 5 NR Retro and pre glandular; subcutaneous avoiding intraglandular injection NR Retro glandular; prefascial; subcutaneous 10 cc syringe Intra muscular; retro glandular; subcutaneous 55/breast 1 NR Associated with inserting or changing implants 187/patient/ session 2 NR 185/breast 1 NR Enrichment in bone-marrow stem cells, taken from iliac crest 236/250 1 NR 2.4 mm canula NR 346 NR NR BRAVA Voglimacci et al 387

11 388 Aesthetic Surgery Journal 35(4) Table 5. Objective Assessment of Volume Gain Article Number of Included Patients Timing of Measurement, in Months After Last Session Volume Measurement Method Fat Resorption Rate Average Volume Gain per Breast in Milliliters (cc), or Chest Measurement in Centimeters (cm) Wang et al, Ultrasonography 57% 1 cm Yoshimura et al, Clinical NR 4 to 8 cm Delay et al, Clinical, 3D interferometry 30% NR Yoshimura et al, Clinical, MRI 20% to 60% 155 cc/143 cc Herold et al, MRI NR 147 cc ± 18 Delay et al, MRI NR NR Ueberreiter et al, MRI NR 110 cc Yang and Lee, Clinical, MRI NR 628 cc Kamakura and Ito, Clinical, MRI NR 3.3 cm Del Vecchio and Bucky, 25 6 MRI NR 272 cc ( ) Del Vecchio, MRI NR Volume equivalent to preoperative (with prosthetic implant) Khouri et al, MRI NR 233 cc ± 108 Auclair et al, MRI 43% (measured in 20 patients) Fiaschetti et al, et 12 MRI 15.36% +/1.76 at 6 months; 28.23% ± 1.55 at 12 months NR NR Bulgin et al, Clinical, MRI NR 5.5 cm Spear and Pittman, Clinical, MRI 36%/39.5% 85 cc/98 cc Khouri et al, MRI NR 266 cc NR, not reported. Rubin et al 54 compared mammographic changes 1 year postoperatively between 27 patients who had undergone fat grafting breast augmentations and 23 patients who had undergone breast reductions. In that study, the radiologists read the mammographies in a blinded fashion, and fat grafting produced comparable radiographic abnormalities, with more favorable breast imaging reports and data system scores for AFG. Oncological Risk Among the 2023 included patients who were followed-up for a mean of 22 months, two patients were diagnosed with breast cancer (0.09% of the study population). These two cases were reported in a case series of 15 patients published by Coleman and Saboeiro in One of the two cases developed cancer in a non-grafted zone and the other in a zone that could have been grafted. No published study was dedicated exclusively to an oncological risk assessment. DISCUSSION Over the last few years the renewed interest in lipofilling has been primarily concerned with its use in breast reconstruction, which has led to discussions in scientific and learned societies. The development of the AFG technique for aesthetic breast augmentation, and discussions about it, were limited until a few years ago. Our bibliographic study included more than 2000 cases of aesthetic breast augmentation by AFG conducted during the last 28 years, and attempted to provide a global view of its current international practice.

12 Voglimacci et al 389 No randomized clinical trial has compared this procedure to the gold standard technique of using prosthesis. Only one German study included patients with breast prostheses as a control population for an MRI volumetric assessment. 50 Furthermore, 41 out of 42 articles had a low evidence level (3, 4, or 5), and the studies were heterogeneous with regard to their inclusion criteria and analyses, so our results must be treated with caution. The geographical distribution of the studies was quite extensive. A British publication in 2013 assessed the practical behavior of 228 plastic and breast surgeons with regard to lipofilling. 56 Among them, 48 of 70 plastic surgeons (69%) and 17 of 158 breast surgeons (11%) used this procedure in routine practice. Despite criticism and the lack of long-term data concerning the oncological and radiological effects, as well as the long-term efficacy, most of the plastic surgeons answered that they practice lipofilling. These observations support the establishment of a national register for surgeons who use this technique, similar to those that exist for organ grafts. In the same way as mammary implants are tagged with serial numbers, this would ensure traceability and accountability. The main operative indication for lipofilling is classic aesthetic breast augmentation, but several studies reported interesting results for malformations. 26,32,38 The latter indication is specific, as the population characteristics are different, the number of cases is restricted, the patients differ in age, and there may be complex mammary glandular architecture or anatomical abnormalities that are difficult to correct with prosthetic implants. Additional studies should confirm the interest in lipofilling for this patient subgroup and integrate the concept of a customized autologous implant. In terms of fat harvesting, processing, and re-injection, the operative procedure lacks standardization and therefore differs among surgical teams. Nonetheless, at present there is no evidence in the literature that supports specific procedural standardization according to Gir et al. 57 The main innovations have been the development of associated techniques to improve graft tissue survival rate, receiving site pre-expansion, and stem cell enrichment. The methods to improve the graft tissue survival rate are encouraging, but their broad application is difficult because of their cost and the constraints of wearing a BRAVA device. There is currently no consensus concerning stem cell enrichment, due to the oncogenic potential of multipotent stem cells. 58,59 The postoperative follow-up differed widely among the studies. In most cases it was clearly scheduled at 1 year postoperatively. Follow-up has been described as late as 25 years postoperatively in large cohorts by Illouz and Sterodimas 46 but concerned only a small sample of patients and was not described systematically in the initial protocol. The learned societies clearly recommend that patients should remain under medical surveillance for the rest of their life. Who should assume the cost of such a follow-up? This problem should also be explained to patients before the procedure. Procedural costs were not well evaluated and differed by country and practitioner. The cosmetic results seemed to be satisfactory according to most authors. The most recently published studies reported injection of ml/breast, with a volume gain equal to or more than one cup. Nevertheless, an objective evaluation of these results was difficult, as measurement methods, particularly when conducted by MRI, were not systematic. Among the 42 publications, only 17 objectively evaluated volume enhancement during the postoperative period, but these evaluations were difficult to interpret due to the heterogeneity of the reported methodologies. Analysis of the data did not lead to conclusive findings concerning the actual volume gain after fat grafting in the healthy breast. In future, the establishment of an MRI-based measurement system that is used in all relevant studies would allow comparisons of the long-term results obtained by different teams. Cosmetic results were rarely assessed by independent practitioners, and should have been compared in a blinded fashion, with prosthetic augmentation as a reference technique. This is really the only way in which a technique can be assessed in comparison to the gold standard. The same observations apply for patient satisfaction, evaluations of which were highly subjective and lacked any validated and reproducible measurement methods. The reported complication rates were low (<15% of procedures), and most were minor. The cytosteatonecrosis rate was notably low when compared to that found during breast reconstruction, which is 5%. 60 This difference is possibly due to an underestimation of cytosteatonecrosis by the authors due to its benign nature, or by better vascularization of the healthy breast than the neoplastic breast, which is traumatized by surgery and radiotherapy, causing less cytosteatonecrosis. As a mammary implant technique, lipofilling can lead to initial complications, including infections, hematoma, inflammatory reactions, and wound dehiscence. However, very few medium- to long-term complications have been reported, demonstrating a significant advantage with this procedure. Prosthetic augmentation historically had a medium- and longterm complication rate of 10%. 61,62 Most of the complications were periprosthetic capsular contracture, nipple sensory loss, late seroma, and ruptured prostheses, 62,63 and they typically occurred several years after initial surgery. This was particularly the case for periprosthetic capsular contracture, which has a low incidence (1 3%) during the first few years after the procedure. 64,65 Hidalgo reported an incidence of secondary surgery of 0 36% over 10 years, with implant failure, capsular contracture, and malposition as the most common causes. 62 Concerning lipofilling, the included studies did not allow for analysis of medium- and long-term complication rates; therefore, our observation of a low complication rate after an average follow-up of 22 months should be

13 390 Aesthetic Surgery Journal 35(4) interpreted with caution. Lazzaretti et al 29 reported a case of a late complication occurring 10 years after AFG, leading to a skin-sparing mastectomy for a giant liponecrotic cyst that appeared like eggshells on mammography. This isolated case is not representative, but it emphasizes the potential for long-term complications. Overall, the lower rate of medium- and long-term complications would support lipofilling, as it would reduce the need for reinterventions. Preoperative patient selection was rarely discussed by the authors. Which patient has a good indication? Who will have a better cosmetic result with lipofilling than with prosthesis? Is lipofilling relevant in underweight patients? Following Chui, 66 a BMI <18.5 does not decrease the breast enlargement observed after lipofilling compared to normal-weight females. Therefore, it is important to determine whether a given patient population is representative of the best candidates for this procedure. The radiological data obtained were highly heterogeneous with regard to follow-up modalities, examination types, radiological criteria, and observed results. No study provided evidence of the interference of lipofilling with breast cancer mammographic screening. Many articles focused on minor radiological changes with this procedure. A trained radiologist finds little difficulty interpreting the images. 53,67,68 Nevertheless, few of the articles used the ACR classification, and long-term effects were almost impossible to assess because most of the radiological controls were performed 12 months after the initial surgery. From comparing mammographic changes after lipofilling versus breast reduction, Rubin et al 54 concluded that lipofilling has a lower impact. However, that study had several methodological weaknesses, as the populations were different (35.9 ± 9.9 years old Japanese vs. 50 ± 8.9 years old American females); the volume differences pre- and postoperatively also differed (the Japanese females received ml of AFG vs an 800-g withdrawal in the American females for breast reduction). Numerous authors presented MRI control results, allowing for the interpretation of suboptimal images, but the feasibility and cost of this type of monitoring in routine practice remains a problem. We found a very low rate of breast cancer: only two cases occurred among more than 2000 included patients. However, the follow-up was limited to a few years, which is insufficient for medium- and long-term breast cancer diagnoses. This insufficient follow-up duration prevents the use of evidencebased medicine principles in drawing conclusions; it is impossible to know if the low rate was due to a lack of effective over-risk or to non-detection of cases. This emphasizes the importance of controlling the long-term follow-up of patients undergoing lipofilling for breast enlargement. The fundamental oncological research emphasizes the importance of the microenvironment in malignant pathology. 69 Interactions between tumor cells and adipocytes are well established, 70 and phenotype-modified adipocytes have been identified as cancer-associated adipocytes. In this context, several studies reported a positive estrogenicdependent effect of adipocytes on the growth of tumor cells and their metastatic potential, 71 but the role of other fat tissue components should also be considered. 72 These theoretical data indicate that injection of fat tissue into a breast should be performed cautiously. However, only a few isolated cases of breast cancer recurrence after lipofilling during breast reconstruction have been published, 13,73,74 and no study has shown that this practice increases the incidence of breast cancer. To establish lipofilling as a routine procedure, it is essential to conduct prospective clinical trials, such as the Adipose Tissue Transfer for Moderate Breast Cancer Conservative Treatment Sequella (GRATSEC) national study, 75 which is currently underway in our unit. If prohibiting the lipofilling of healthy breasts is unreasonable, its practice must be clearly and strictly regulated by learned societies or sanitary authorities. We have observed an explosive increase in the use of this procedure because of the ease with which it can be performed and a lack of legal and scientific supervision. We fear that increasing numbers of surgeons will practice this technique without relevant information, preoperative imaging, adequate skills, or appropriate follow-up procedures. We found that recommendations of best practices were not applied systematically. The recommendations of the SoFCPRE consider lipofilling during breast augmentation as a surgical option, in cases with a low breast cancer risk (age <35 years and no personal or family history of breast cancer). A preoperative radiological control (mammography and ultrasonography) conducted by a trained radiologist is necessary, and a normal appearance (ACR 1 or 2) is a condition sine qua non for the surgery. Furthermore, patients must commit to obtaining the radiologic control one year after surgery and remain under regular medical monitoring. However, which specialist should perform this monitoring and what type of monitoring should be conducted (eg, clinical or complementary examination, frequency, etc) are unclear. American recommendations suggest that the procedure is safe under some medical conditions. 8 Nonetheless, with high-risk breast cancer patients (BRCA-1/BRCA-2 mutation and a personal or family history of breast cancer), it seems safer to avoid AFG completely. The ASPS guidelines also specify that informed consent must be obtained and that patients should be informed that scientific data concerning the efficacy and safety of the procedure are limited. BAAPS also provided recommendations in 2012 that essentially limit the indications for lipofilling to treatment of sequelae after breast conservation surgery. Furthermore, a preoperative radiological control is required, as well as regular radiographic follow-up for several years. Official documents for patients issued by the above-mentioned

14 Voglimacci et al 391 institutions include these recommendations as part of the preoperative information. Finally, learned societies agree on the following points: - Exclude patients at high risk for breast cancer. - Conduct a preoperative radiological check-up. - Conduct regular postoperative medical follow-ups. The recommendations differ among countries regarding preoperative patient selection and practical modalities for follow-up. The current thinking in the US regarding postlipofilling screening is the same as for the general public. Mammograms have been shown to be safe and effective in detecting lesions in patients who have undergone fat grafting. The current protocol for cancer screening recommended by the American College of Surgeons should be sufficient for women undergoing lipofilling as well. Nevertheless, no clear recommendations concerning postoperative follow-up procedures (in terms of clinical and radiological exams and also the periodicity of follow-up) are available in the US or in any other countries at this time. Experts emphasize the operator-dependent character of the procedure, and the lack of high-level scientific evidence in publications. All recommendations considered lipofilling as a surgical option reserved for particular indications and to be performed only by trained and skilled surgeons. Prosthetic breast augmentation remains the reference technique for most cases. A limitation of this study was the large heterogeneity among lipofilling practices in native breast. The low level of evidence in the majority of the articles did not allow us to reach firm conclusions regarding several aspects of this procedure, which would require long-term, high-level evidence studies. CONCLUSION The literature analysis revealed this aesthetic breast augmentation procedure to be an easy-to-perform and reliable technique, with satisfactory results and few complications. The long-term results are largely unknown, but the procedure seems to be safe and is becoming a useful and practical tool in plastic surgery. Preoperative patient selection to define a good indication was not discussed in the reviewed studies and requires further investigation. AFG for breast enlargement is a surgical option for which the indication must be evaluated on a case-by-case basis. The recommendations must be strictly applied, due to the lack of scientific evidence. The surgeon must be aware of the current state of knowledge, keep the patient fully informed, and understand the necessity for postoperative medical follow-ups. This procedure should be reserved for trained and highly-skilled teams, and supported by an official national or international registry. This registry would allow the collection of prospective data, which would validate the procedure in accordance with evidencebased medical principles. Homogenization of the recommendations should be clarified on an international scale. Disclosures The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. ISAPS International Survey on Aesthetic/Cosmetic Procedures Performed in news/isaps-global-statistics. Accessed July 24, Cosmetic Surgery National Data Bank: Statistics Aesthet Surg J. 2014;34(1 suppl):1s-22s. 3. Neuber F. Fettransplantation. Chir Kongr Verhandl Dtsch Ges Chir. 1893;22: Czerny V. Plastic replacement of the breast with a lipoma. Chir Kongr Verhandl Dtsch Ges Chir. 1895;7(2): American Society of Plastic and Reconstructive Surgeons (AS-PRS). Ad-hoc committee on new procedures. Report on autologous fat transplantation. Plast Surg Nurs. 1987; 7: Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthet Plast Surg. 1995;19:421e5. 7. Coleman SR. Facial recontouring with lipostructure. Clin Plast Surg. 1997;24:347e Gutowski KA, ASPS Fat Graft Task Force. Current applications and safety of autologous fat grafts: a report of the ASPS Fat Graft Task Force. Plast Reconstr Surg. 2009; 124: Tansfert graisseux dans les cas d augmentation mammaire a visée esthétique ou pour malformations congénitales. 14_Tansfert_graisseux_%20augmentation_mammaire_a_ visee_esthetique_ou_malformations_congenitales.pdf. Accessed November Garrido I, Leguevaque P, Gangloff D, Mojallal A. [The adipose tissue transfer in the mammary parenchyma ( part II): Review of the literature on the carcinologic risks]. Ann Chir Plast Esthet. 2011;56: Hyakusoku H, Ogawa R, Ono S, Ishii N, Hirakawa K. Complications after autologous fat injection to the breast. Plast Reconstr Surg. 2009;123: ; discussion Wang C-F, Zhou Z, Yan Y-J, Zhao D-M, Chen F, Qiao Q. Clinical analyses of clustered microcalcifications after autologous fat injection for breast augmentation. Plast Reconstr Surg. 2011;127: Chaput B, Grolleau JL, Bertheuil N, Eburdery H, Chavoin JP, Garrido I. Another suspected case of breast cancer

15 392 Aesthetic Surgery Journal 35(4) recurrence after lipofilling? Remain cautious. J Plast Reconstr Aesthet Surg. 2014;67(8): PROSPERO International prospective register of systematic reviews. record.asp?id=crd #.u5gjdxyysc8.accessed May Fat Transfer to Breast. fat-transfer-to-breast. Accessed Bircoll M, Novack BH. Autologous fat transplantation employing liposuction techniques. Ann Plast Surg. 1987;18: Bircoll M. Cosmetic breast augmentation utilizing autologous fat and liposuction techniques. Plast Reconstr Surg. 1987;79: Hörl HW, Feller AM, Biemer E. Technique for liposuction fat reimplantation and long-term volume evaluation by magnetic resonance imaging. Ann Plast Surg. 1991;26: Maillard GF. Liponecrotic cyst after augmentation mammaplasty with fat injections. Aesthet Plast Surg. 1994;18: Castello JR, Barros J, Vazquez R. Giant liponecrotic pseudocyst after breast augmentation by fat injection. Plast Reconstr Surg. 1999;103: Valdatta L, Thione A, Buoro M, Tuinder S. A case of lifethreatening sepsis after breast augmentation by fat injection. Aesthet Plast Surg. 2001;25: Kwak JY. Sonographic identification of complications of cosmetic augmentation with autologous fat obtained by liposuction. Ann Plast Surg. 2004;64: Pulagam SR, Poulton T, Mamounas EP. Long-term clinical and radiologic results with autologous fat transplantation for breast augmentation: case reports and review of the literature. Breast J. 2006;12: Wang H, Jiang Y, Meng H, Yu Y, Qi K. Sonographic assessment on breast augmentation after autologous fat graft. Plast Reconstr Surg. 2008;122:36e-38e. 25. Carvajal J, Patiño JH. Mammographic findings after breast augmentation with autologous fat injection. Aesthet Surg J. 2008;28: Pinsolle V, Chichery A, Grolleau J-L, Chavoin JP. Autologous fat injection in Poland s syndrome. J Plast Reconstr Aesthet Surg. 2008;61: Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthet Plast Surg. 2008;32:48-55; discussion Mu D, Luan J, Mu L, Xin M. Breast augmentation by autologous fat injection grafting: management and clinical analysis of complications. Ann Plast Surg. 2009;63: Lazzaretti MG, Giovanardi G, Gibertoni F, Cagossi K, Artioli F. A late complication of fat autografting in breast augmentation. Plast Reconstr Surg. 2009;123:71ee2e. 30. Yoshimura K, Asano Y, Aoi N, et al. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2009;16: Lee KS, Seo SJ, Park MC, et al. Sepsis with multiple abscesses after massive autologous fat grafting for augmentation mammoplasty: a case report. Aesthet Plast Surg. 2011;35: Delay E, Sinna R, Chekaroua K, Delaporte T, Garson S, Toussoun G. Lipomodeling of Poland s syndrome: a new treatment of the thoracic deformity. Aesthet Plast Surg. 2010;34: Talbot SG, Parrett BM, Yaremchuk MJ. Sepsis after Autologous Fat Grafting. Plast Reconstr Surg. 2010;126: 162e-164e. 34. Kim H, Yang E-J, Bang S-I. Bilateral Liponecrotic Pseudocysts After Breast Augmentation by Fat Injection: A Case Report. Aesthet Plast Surg. 2012;36: Yang H, Lee H. Successful use of squeezed-fat grafts to correct a breast affected by Poland syndrome. Aesthet Plast Surg. 2011;35: Kamakura T, Ito K. Autologous Cell-Enriched Fat Grafting for Breast Augmentation. Aesthet Plast Surg. 2011;35: Del Vecchio DA. SIEF --simultaneous implant exchange with fat: a new option in revision breast implant surgery. Plast Reconstr Surg. 2012;130: La Marca S, Delay E, Toussoun G, Ho Quoc C, Sinna R. [Treatment of Poland syndrome thorax deformity with the lipomodeling technique: about ten cases]. Ann Chir Plast Esthet. 2013;58: Auclair E, Blondeel P, Del Vecchio DA. Composite Breast Augmentation: Soft-Tissue Planning Using Implants and Fat. Plast Reconstr Surg. 2013;132: Bulgin D, Vrabic E, Hodzic E. Autologous bone-marrowderived-mononuclear-cells-enriched fat transplantation in breast augmentation: evaluation of clinical outcomes and aesthetic results in a 30-year-old female. Case Rep Surg. 2013; 2013: Matsudo PK, Toledo LS. Experience of injected fat grafting. Aesthet Plast Surg. 1988;12: Coleman SR, Saboeiro AP. Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg. 2007;119: ; discussion Zheng DN, Li QF, Lei H, et al. Autologous fat grafting to the breast for cosmetic enhancement: experience in 66 patients with long-term follow up. J Plast Reconstr Aesthet Surg. 2008;61: Zocchi M, Zulani F. Bicompartmental breast lipostructuring. Aesthet Plast Surg. 2008;32: Delay E, Garson S, Tousson G, Sinna R. Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009;29: Illouz YG, Sterodimas A. Autologous fat transplantation to the breast: a personal technique with 25 years of experience. Aesthet Plast Surg. 2009;33: Herold C, Ueberreiter K, Vogt PM. Brava and autologous fat transfer is a safe and effective breast augmentation alternative: results of a 6-year, 81-patient, prospective multicenter study. Plast Reconstr Surg. 2012;130:479e-480e. 48. Ueberreiter K, von Finckenstein JG, Cromme F, Herold C, Tanzella U, Vogt PM. BEAULI --a new and easy method