autologous breast reconstruction bjs

Systematic review

Applicability and safety of autologous fat for reconstructionof the breast

F. Claro Jr1,2, J. C. A. Figueiredo2, A. G. Zampar2 and A. M. Pinto-Neto1

1Department of Gynaecology and Obstetrics, School of Medical Sciences, State University of Campinas, Campinas, and 2Santa Cruz Plastic SurgeryInstitute, Sao Paulo, BrazilCorrespondence to: Dr F. Claro Jr, Departamento de Ginecologia e Obstetrıcia da Faculdade de Ciencias Medicas da UNICAMP, R. Alexander Fleming,101, 13083-881 Campinas, SP, Brazil (e-mail: [email protected])

Background: Autologous fat grafting to the breast for cosmetic and reconstructive purposes is stillcontroversial with respect to its safety and efficacy. The objective of this study was to conduct asystematic review of the clinical applicability and safety of the technique.Methods: An online search of the Cochrane Library, MEDLINE, Embase and SciELO was conductedfrom July 1986 to June 2011. Studies included in the review were original articles of autologousliposuctioned fat grafting to the female breast, with description of clinical complications and/orradiographic changes and/or local breast cancer recurrence.Results: This review included 60 articles with 4601 patients. Thirty studies used fat grafting foraugmentation and 41 for reconstructive procedures. The incidence of clinical complications, identifiedin 21 studies, was 3·9 per cent (117 of 3015); the majority were induration and/or palpable nodularity.Radiographic abnormalities occurred in 332 (13·0 per cent) of 2560 women (17 studies); more than halfwere consistent with cysts. Local recurrence of breast cancer (14 of 616, 2·3 per cent) was evaluated inthree studies, of which only one was prospective.Conclusion: There is broad clinical applicability of autologous fat grafting for breast reconstruction.Complications were few and there was no evidence of interference with follow-up after treatment forbreast cancer. Oncological safety remains unclear.

Paper accepted 2 February 2012Published online 4 April 2012 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.8722

Introduction

The transfer of autologous fat for surgical reconstructiondates back to 1893, when Neuber described implantinga small piece of upper arm fat tissue to correct a scardepression in the face1,2. Since then, fat tissue has beenemployed for the correction of multiple body deformities3,4

and was reported to be the source of the first breastreconstruction. In 1895, Czerny used a large lipoma fromthe dorsal flank for breast reconstruction after excision ofa benign lesion5,6.

With the advent of liposuction in the 1970s, aspiratedfat could be reinjected without any preparation by plasticsurgeons7,8. Fat grafting has become widely used ingynaecological, urological, neurological, orthopaedic, ear,nose and throat, trauma and thoracic surgery. It is efficientin correcting deformities in virtually all body areas andis widely used in cosmetic procedures3,4,9,10. Unlike other

body areas, aesthetic and reconstructive results in the breastremained unsatisfactory, together with the appearance ofmany complications11,12. Furthermore, it was suggestedthat adipocytes might stimulate the formation of breastcancer or induce radiographic changes if used after breastcancer surgery. This could compromise the detectionof recurrence or new malignant lesions. In 1987, theAmerican Society of Plastic Surgeons prohibited the use ofautologous fat grafting to the female breast13.

Subsequently, Coleman14,15 formulated new concepts,standardizing the technique of structural fat grafting.This then became the therapeutic method used invarious surgical specialties for cosmetic and reconstructivepurposes.

In breast reconstruction, unlike elsewhere in the body,adipocytes are implanted in a poorly vascularized and loosespace. Therefore, the fat needs greater contact with the host

2012 British Journal of Surgery Society Ltd British Journal of Surgery 2012; 99: 768–780Published by John Wiley & Sons Ltd

Autologous fat for reconstruction of the breast 769

tissue to ensure adequate nutrition and immobilization foradipocyte survival in the first few days, as the adipocytesbecome incorporated. These anatomical characteristics inthe breast explain the poor results and the high rate ofcomplications. The concept of structural fat grafting is thatthe fat must be inserted in small amounts using multipletunnels, in many layers and directions, so that the largestpossible number of adipocytes are in contact with hosttissue and thus receive adequate nutrition for their survival(Fig. 1)14. Thin cannulas (1·2–3 mm) and syringes of lowvolume (1–20 ml) allow greater accuracy, avoiding bolusinjections (Fig. 2). Several authors used this method10,16–19

before it was formally described by Coleman. Anynecrotic tissue that is not completely absorbed causes aninflammatory reaction, resulting in fibrosis and/or cysticformation, with or without calcification, and also localinfection20–23.

A number of studies using structural fat grafting to thebreast have been published, with good results16,17,24. Thisled to renewed interest in the procedure; however, fatgrafting still raises doubts with respect to indication andsafety in clinical practice. In 2009, the American Society ofPlastic Surgeons did not prohibit the procedure (owing tolack of evidence), although they did not recommend it25.

The aim of this study was to identify the indications andsafety of the procedure, by means of a systematic review ofclinical complications, radiographic changes and incidenceof breast cancer (primary or recurrent) in women treatedwith fat grafting to the breast.

Fig. 1 Structural fat grafting. The fat is grafted in small amountsvia multiple tunnels in many layers, avoiding the gland tissue, asillustrated on the left breast with directions shown on the rightbreast. Thus the largest possible number of adipocytes are incontact with the host tissue and receive adequate nutrition forsurvival

Fig. 2 Thin cannulas (1·2–3 mm) and low-volume syringes(1–20 ml) allow greater accuracy of the amount grafted pertunnel, avoiding bolus injection. After preparation of theliposuctioned material (in the three syringes in the verticalposition), the lower and uppermost levels are discharged. Themiddle layer contains the viable adipocytes

Methods

Search strategy

A systematic review of autologous fat grafting to thefemale breast was conducted according to the guidelinesin the Preferred Reporting Items for Systematic Reviewsand Meta-Analyses (PRISMA) statement26. The searchfor articles published in the past 25 years (from July1986 to June 2011) was carried out independently bytwo reviewers after accessing the electronic databases ofthe Cochrane Library, US National Library of Medicine(MEDLINE), Embase and Scientific Electronic LibraryOnline (SciELO). Appropriate keywords in the Englishlanguage were combined by Boolean logical operators,as follows: ‘fat autografting’ OR ‘fat grafting’ OR ‘fatautograft’ OR ‘fat graft’ OR ‘fat transplantation’ OR‘fat injection’ OR ‘autologous fat’ OR ‘lipostructuring’OR ‘lipotransfer’ OR ‘lipomodelling’ OR ‘lipomodeling’AND ‘breast’, adapted to the appropriate syntax of eachdatabase. Studies that were considered potentially relevantbased on titles were cross-referenced in a search foradditional articles of potential interest, with no restrictionon language, type of study or publication media.

Inclusion criteria

Original articles concerning autologous fat grafting tothe human female breast, with fat recently removed

2012 British Journal of Surgery Society Ltd www.bjs.co.uk British Journal of Surgery 2012; 99: 768–780Published by John Wiley & Sons Ltd

770 F. Claro Jr, J. C. A. Figueiredo, A. G. Zampar and A. M. Pinto-Neto

by liposuction, were eligible for inclusion in thisreview. Only articles that mentioned results such asclinical complications and/or radiographic changes and/orincidence of breast cancer in patients treated with thepreviously described technique were included.

Exclusion criteria

Duplicate articles were excluded. Studies using recentlyaspirated mature adipocytes in a proportion lower than50 per cent, characterizing stem cell implants, and thosethat did not contain a description of the indication forthe procedure were not considered eligible for this review.Articles without original data, such as reviews or technicaldescriptions, were also ineligible.

Study selection

Abstracts of studies initially selected were evaluated by allfour reviewers independently to determine eligibility. Inthis case the full text of articles was retrieved for evaluation,data extraction and inclusion in the systematic review.When a selected study was not available in the electronicmedia or local libraries, the authors were contacted torequest a copy27.

Extraction of data

Data extracted from articles included: authors, dateof publication, number of subjects, indication for theprocedure, type of study, technique used for adipocyteimplantation, follow-up time, efficacy of treatment,clinical complications, radiographic changes, and incidenceof primary and recurrent breast cancer. They wereextracted independently and tabulated by two reviewers;discrepancies were discussed and reviewed by all fourreviewers until agreement was reached.

In clinical trial articles and observational cohort studies,case–control and case series with more than 20 patients, theoutcomes of interest previously defined were: indication,efficacy, clinical complications, radiological changes andbreast cancer. Although efficacy was described in asubjective and widely heterogeneous way among thestudies, it was presented according to the original authors’assessment. Case reports and case series with up to20 patients were used only as an additional sourcefor the summation analysis of types of complicationand radiographic changes, but were excluded from theassessment of their rates because of the likelihood of bias.

Assessment of study quality

The methodological quality of the studies was assessedby two independent reviewers; level of evidence andgrade of recommendation were scored according tothe criteria of the Oxford Centre for Evidence-basedMedicine28, and Grading of Recommendation Assessment,Development and Evaluation (GRADE)29. Observationalstudies and clinical trials lacking a detailed description ofthe randomization procedure were considered to have ahigh potential for bias30–32.

Statistical analysis

Outcomes of interest were tabulated, and shown in descrip-tive and individual form, considering the methodologicalquality of each study. The prevalence of clinical complica-tions and radiological changes was identified. Meta-analysiswas not done because of the heterogeneous methodologyamong studies30–32.

Results

A database search for the prespecified keywords identified302 articles (171 in Embase, 131 in MEDLINE and nonein the Cochrane Library or SciELO). After exclusionof duplicate articles and manual cross-referencing, twonew articles were included33,34, giving a total of 95.Of these, 23 articles were excluded after reading theabstracts and 72 were eligible for full-text reading.Among these, one was excluded for using fat blocktransplantation instead of liposuction35, two for using morethan 50 per cent immature adipocytes, which characterizesstem cell transplantation36,37, two for failing to recordthe outcomes of interest38,39 and seven that wereapparently repeat case studies40–46. Sixty articles (4601women) remained and were used in this systematicreview6,11,12,16–19,24,27,33,34,47–95. Only 27 articles wereassessed for incidence of clinical complications and/orradiological findings and/or breast cancer (Fig. 3). Of these,21 studies that included 3015 women were used to extractthe incidence of clinical complications, 17 studies with2560 women to calculate the incidence of radiographicchanges, and three studies with 616 women to evaluateoncological risk.

There were 58 observational studies: 37 case reportsand case series, seven retrospective cohort studies, 12prospective cohort studies, one diagnostic validation cohortstudy and one case–control study. Two studies were clinicaltrials without a description of the randomization. Themethodology and quality of each study are shown in Table 1.



Records identified by databasesearching n = 302 Embase = 171 MEDLINE = 131 SciELO = 0 The Cochrane Library = 0

Records after duplicates removedn = 167

Records screened for more detailedevaluation after reading title n = 95

Full-text articles assessed for eligibilityn = 72

Studies included in the systematicreview n = 60 Article assessed for incidence of clinical complications, radiological findings and breast cancer n = 27

Studies of potential interest identified by cross-referencing n = 2

Records excluded after reading abstract as failedinclusion/exclusion criteria n = 23

Articles excluded after reading full text n = 12 Fat block transplantation n = 1 Duplicate database n = 7 No numerical data on outcomes n = 2 Used more than 50% immature adipocytes n = 2

Fig. 3 Selection of articles for review

Clinical applicability

Thirty of the studies, with at least 930 patients, used fatgrafting to the breast for aesthetic augmentation; 41 studieswith more than 3646 patients described the procedure forbreast reconstruction. The majority of these articles wereconsidered to be of low or very low quality according to theGRADE criteria. In general, the procedure was reportedas being satisfactory (Table 1).

Clinical indications for autologous fat grafting accordingto the GRADE criteria for methodological qualityare illustrated in Fig. 4. In the aesthetic field, themain indication for the procedure was primary breastaugmentation (30 studies including about 1000 women),followed by secondary augmentation after removal of analloplastic implant, or to improve the contour of the breastsafter placement of the implant. All studies investigatingthese indications were observational. Most consisted ofcase reports and case series, of low or very low quality. Inthe reconstructive field, the procedure was used mainly forpartial breast reconstruction and/or correction of breastdeformities. This was the second most frequent indication

(15 studies, more than 365 women), followed by totalbreast reconstruction. In more recent studies (starting in2009), autologous fat grafting was reported as therapy forpostradiotherapy radiodermatitis67,84 and as treatment forcapsular contracture in breasts with alloplastic implants80

(Fig. 4).

Safety

Clinical complicationsInitially, all 60 studies were evaluated for clinicalcomplications, which were identified in 155 of 4601patients. Nodularity and/or induration was identified in 93patients (60·0 per cent), followed by deep infection in 19(12·3 per cent). There was no recorded death. Three casesof sepsis were identified in case reports of complicationswhen structured fat grafting was not used (Fig. 5). In oneof these, the patient received fat grafting to the breasts andbuttocks. She developed abscesses in one breast and in onegluteal region, requiring open drainage for both regions33.

Considering the 21 studies with better methodologicalquality, which described fixed follow-up, a standard



Table 1 Characteristics of included studies

No. of patients (breasts)

Reference Year Study design GRADE* Cosmetic augmentation Reconstruction Efficacy

Bircoll18 1987 Case report Very low 1 (2) – SatisfactoryBircoll and Novack19 1987 Case report Very low – 1 (1) SatisfactoryHorl et al.11 1989 Case report Very low 1 (2) – RCCMaillard12 1994 Case report Very low 1 (2) – RCCUchiyama et al.47 2000 Case report Very low 3 (6) – RARCheung et al.48 2000 Case report Very low 1 (2) – RARValdatta et al.49 2001 Case report Very low 1 (2) – RCCGulsun et al.50 2003 Case report Very low 1 (2) – RARKwak et al.51 2004 Case report Very low 1 (2) – RARSpear et al.24 2005 Retrospective cohort Low – 43 SatisfactoryPierrefeu-Lagrange et al.52 2006 Case series Low – 30 (34) SatisfactoryPulagam et al.53 2006 Case report Very low 1 (2) 1 (1) RARColeman and Saboeiro6 2007 Retrospective cohort Low 10 (20) 7 (11) SatisfactoryMissana et al.54 2007 Retrospective cohort Low – 74 SatisfactoryYoshimura et al.55 2008 Retrospective cohort Low 40 (80) – SatisfactoryCotrufo et al.56 2008 Case series Low – 42 SatisfactoryGosset et al.57 2008 Case series Low – 21 SatisfactoryPinsolle et al.58 2008 Case series Low – 7 SatisfactoryMojallal et al.27 2008 Case report Very low – 1 SatisfactoryZheng et al.59 2008 Case series Low 47 19 SatisfactoryZocchi and Zuliani60 2008 Retrospective cohort Low 181 (326) – SatisfactoryCarvajal and Patino61 2008 Case series Low 20 (40) – RARWang et al.62 2008 Case series Low 33 (66) – RARKaufman et al.63 2009 Prospective cohort Low – 9 (9) SatisfactoryElFadl et al.64 2009 Prospective cohort Low 1 21 SatisfactoryDelaporte et al.65 2009 Prospective cohort Low – 15 (15) SatisfactoryHyakusoku et al.66 2009 Case series Low 12 (24) – RCCPanettiere et al.67 2009 Clinical trial Moderate – 22 (22) SatisfactoryKanchwala et al.68 2009 Retrospective cohort Low – 110 SatisfactoryDel Vecchio69 2009 Case report Very low 1 (2) – SatisfactoryMu et al.70 2009 Case series Very low 17 (34) – RCCLazaretti et al.71 2009 Case report Very low 1 (2) – RCCDelay et al.17 2009 Case series Low 30 850 SatisfactoryIllouz and Sterodimas16 2009 Case series Low 385 (770) 435 (478) SatisfactorySalgarello et al.72 2010 Case report Very low – 2 (2) SatisfactoryPereira and Sterodimas73 2010 Case report Very low – 1 (2) SatisfactoryBabovic74 2010 Case report Very low – 1 (1) SatisfactoryRigotti et al.75 2010 Clinical trial Moderate – 911 SatisfactorySerra-Renom et al.76 2010 Case series Low – 65 (65) SatisfactoryErol et al.77 2010 Case report Very low 1 (2) 1 (1) RCCTalbot et al.33 2010 Case report Very low 1 (2) – RCCWang et al.78 2010 Prospective cohort Low 41 (82) – RARVillani et al.79 2010 Case series Low – 5 (5) SatisfactoryUeberreiter et al.80 2010 Prospective cohort Low 52 (104) 33 SatisfactoryVeber et al.81 2011 Diagnostic validation cohort Moderate 44 32 SatisfactoryDel Vecchio and Bucky82 2011 Prospective cohort Low NS NS SatisfactoryPettus et al.34 2011 Case report Very low – 1 (2) RARRietjens et al.83 2011 Prospective cohort Low 1 (2) 157 (192) SatisfactoryPanettiere et al.84 2011 Case report Very low – 1 (2) SatisfactorySerra-Renom et al.85 2011 Prospective cohort Low – 28 (56) SatisfactorySerra-Renom et al.86 2011 Prospective cohort Low – 8 (9) SatisfactoryLee et al.87 2011 Case report Very low 1 (2) – RCCSarfati et al.88 2011 Prospective cohort Low – 28 SatisfactoryLosken et al.89 2011 Case series Low – 107 SatisfactoryYang and Lee90 2011 Case report Very low – 1 (1) SatisfactoryYoung and Zellner91 2011 Case series Low – 100 (130) SatisfactoryMurphy et al.92 2011 Prospective cohort Low – 100 Satisfactory

(Continued overleaf)



Table 1 (Continued)

No. of patients (breasts)

Reference Year Study design GRADE* Cosmetic augmentation Reconstruction Efficacy

Beck et al.94 2012 Prospective cohort Low – 10 SatisfactoryIrani et al.95 2012 Retrospective cohort Low – 25 (25) SatisfactoryPetit et al.93 2012 Case–control Moderate – 321 NR

Overall 930 + NS 3646 + NS

*Methodological quality according to Grading of Recommendation Assessment, Development and Evaluation (GRADE) classification29. RCC, report ofclinical complication; RAR, report of radiological alteration; NS, number of patients not specified; NR, not reported.

(928 + NS)

(365 + NS)

(524 + NS)

(325 + NS)

(59 + NS)

(74 + NS)

(26 + NS)

(133)

(273 + NS)

(46 + NS)

(27)

Methodology quality accordingto GRADE

Very low quality

(21)

(15)

Aesthetic augmentation

Partial breast reconstruction or correction ofdeformities

Total breast reconstruction associated withmyocutaneous flaps

Total breast reconstruction associated withbreast implant

Poland's syndrome or congenital deformity

Total breast reconstruction associated withmyocutaneous flaps and breast implant

Total breast reconstruction with fat grafting alone

Total breast reconstruction before implantation ofbreast prosthesis or myocutaneous flaps

Augmentation after removal of breast implant

Tuberous breast

Cosmetic improvement after breast implant

Treatment of radiological sequelae

Treatment of capsular contracture

0 5 10 15 20 25 30No. of studies

Low quality

Moderate quality

High quality

Fig. 4 Indications for autologous fat grafting to the breast in relation to methodological quality of studies assessed according to theGrading of Recommendation Assessment, Development and Evaluation criteria. Numbers of patients are shown in parentheses. NS,number of patients not specified

(60·0)Palpable induration/nodule

Deep infection

Dysaesthesia

Haematoma

Superficial infection

Pain

Sepsis

Abnormal breast secretion

Pneumothorax

(12·3)

(9·0)

(7·7)Structured fat grafting

(5·8)

(1·9)

(1·9)

(0·6)

(0·6)

100 20 30 40 50 60 70 80 90

No. of complications

Non-structured fat grafting

Fig. 5 Distribution of 155 complications described in 60 studies according to fat grafting technique. Values in parentheses arepercentages



Table 2 Incidence of clinical complications after fat grafting in studies with better methodological quality

Reference Year No. of patients Technique Mean follow-up (months) Clinical complications

Spear et al.24 2005 37 Structured fat graft 15 3 of 37Missana et al.54 2007 69 Structured fat graft 12 0 of 69Yoshimura et al.55 2008 40 Structured fat graft 6 0 of 40Cotrufo et al.56 2008 42 Structured fat graft 7 1 of 42Zheng et al.59 2008 66 Structured fat graft 37 1 of 66Zocchi and Zuliani60 2008 181 Structured fat graft 12 19 of 181Wang et al.62 2008 33 Non-structured fat graft 3 14 of 33ElFadl et al.64 2009 22 Structured fat graft 5 2 of 22Kanchwala et al.68 2009 110 Structured fat graft 21 0 of 110Delay et al.17 2009 880 Structured fat graft 12 35 of 880Illouz and Sterodimas16 2009 820 Structured fat graft 12 17 of 820Serra-Renom et al.76 2010 65 Structured fat graft 12 0 of 65Ueberreiter et al.80 2010 85 Structured fat graft 6 2 of 85Del Vecchio and Bucky82 2011 25 Structured fat graft 6 0 of 25Rietjens et al.83 2011 158 Structured fat graft 18·3 7 of 158Serra-Renom et al.85 2011 28 Structured fat graft 12 0 of 28Sarfati et al.88 2011 22 Structured fat graft 17 0 of 22Losken et al.89 2011 107 Structured fat graft 8 12 of 107Young and Zellner91 2011 100 Structured fat graft 8 2 of 100Murphy et al.92 2011 100 Structured fat graft NR 0 of 100Irani et al.95 2012 25 Structured fat graft 6 2 of 25

Overall 3015 12·35 117 of 3015 (3·9)

Values in parentheses are percentages.

89·4

74·613·4

5·44·7

2·0

Mammography

Solid mass (hypoechoic or isoechoic area)

Sclerotic nodule

15 30 45 60 75 90

Cyst and liponecrotic cyst

Cyst and solid massCyst (anechoic area)

Mass with or without calcificationIncreased density

Benign-type calcificationsMicrocalcification

Cyst

Ultrasound imaging

Magnetic resonance imaging

% of abnormalities

6·04·5

65·234·8

Fig. 6 Prevalence of radiological changes identified in 60 studies among 299 abnormal findings described on mammography, 331 onultrasound imaging and 46 on magnetic resonance imaging

technique and more than 20 patients, the incidence ofclinical complications was 3·9 per cent (117 of 3015)(Table 2). Among these, the most serious complicationreported was pneumothorax (Fig. 5).

Radiographic changesA total of 299 abnormal radiological findings were iden-tified on mammography during follow-up; 74·6 per centwere consistent with cysts and 13·4 per cent with micro-calcification. On ultrasound imaging, 89·4 per cent ofthe 331 radiographic changes were consistent with cystand/or liponecrotic cysts. Magnetic resonance imaging

also showed images consistent with cystic change in65·2 per cent of the 46 findings identified, and nodula-tion in 34·8 per cent (Fig. 6). The overall rate of abnormalradiological findings during follow-up was 13·0 per cent(332 of 2560 patients), taken from the studies with bettermethodology (Table 3).

Breast cancer riskThree studies that evaluated 616 patients (mean follow-up45·2 months) were used to identify the oncological risk inwomen with breast cancer treated with fat grafting. Four-teen recurrent cancers were described (2·3 per cent)75,83,93.



Table 3 Incidence of radiographic changes

Reference Year No. of patients Technique Mean follow–up (months) Radiological changes

Pierrefeu-Lagrange et al.52 2006 30 Structured fat graft 12 12 of 30Missana et al.54 2007 69 Structured fat graft 12 5 of 69Yoshimura et al.55 2008 40 Structured fat graft 6 2 of 40Gosset et al.57 2008 21 Structured fat graft 12 18 of 21Zheng et al.59 2008 66 Structured fat graft 37 11 of 66Zocchi and Zuliani60 2008 181 Structured fat graft 12 7 of 181Wang et al.62 2008 33 Non-structured fat graft 3 14 of 33ElFadl et al.64 2009 22 Structured fat graft 5 2 of 22Delay et al.17 2009 880 Structured fat graft 12 176 of 880Illouz and Sterodimas16 2009 820 Structured fat graft 12 17 of 820Wang et al.78 2010 41 Non-structured fat graft 16 34 of 41Ueberreiter et al.80 2010 85 Structured fat graft 6 0 of 85Veber et al.81 2011 31 Structured fat graft 12 20 of 31Del Vecchio and Bucky82 2011 25 Structured fat graft 6 0 of 25Rietjens et al.83 2011 79 Structured fat graft 18·3 4 of 79Losken et al.89 2011 107 Structured fat graft 8 1 of 107Murphy et al.92 2011 30 Structured fat graft NR 9 of 30

Overall 2560 12·3 332 of 2560 (13·0)

Values in parentheses are percentages.

In all these women the initial treatment was mastectomyfor breast cancer. No report described a new primary breastcancer.

Discussion

This systematic review was performed with informationfrom different studies using a wide range of methods.The majority had a low grade of recommendation, witha high likelihood of bias30–32. Despite these difficultiesand some limitations, after organization and assessmentof the results it was possible to demonstrate the relativesafety of autologous fat grafting to the female breast withfat removed by recent liposuction for the aesthetic andreconstructive treatment of diverse breast disorders.

Although some studies recorded the site of fat harvestand its method of preparation, previous studies havenot reported any effect on the outcomes96–100 so thesetechnical aspects were not studied here. Fat is usuallyharvested from the abdomen, hip and inner thigh. Mostauthors centrifuge the liposuctioned material at 3000 r.p.m.for 3 min, as this gives a higher adipocyte concentration,allowing greater predictability of outcome.

The technique is carried out mainly for aesthetic breastaugmentation (30 of 60 articles used in this review). Mostarticles were observational and there were not enough datato provide an accurate assessment of efficacy. This will beassessed in ongoing prospective studies.

In the field of breast reconstruction, the articles werealso observational and descriptive; however, it was possibleto conclude that fat grafting may be used for total and

partial reconstruction, and usually requires more than oneapplication session. It may also be used in combinationwith myocutaneous flaps, such as the transverse rectusabdominis myocutaneous flap, latissimus dorsi muscleflap or even free microsurgical flaps, to improve breastshape and volume. In addition, fat grafting may be usedwith alloplastic implants, to prepare the recipient sitein women with thin subcutaneous tissue or previouslyirradiated skin67. Other improvements in irradiated skininclude ulcer healing and regeneration of fibrotic areasof the breast36,67,84. Finally autologous fat grafting hasbeen used successfully to correct congenital deformitiessuch as Poland’s syndrome6,16,27,58,81,82,83,90 and tuberousbreast6,81,85.

In this review, the authors found 155 reportedcomplications among 4601 women treated with breast fatgrafting in the 60 studies identified. Most of the reportedcomplications (60·0 per cent) were breast mass and/orinduration, disorders of low morbidity and commonlyreported after breast surgery. Fat grafting uses the patient’sown tissue, so an immune response is not elicited. Threecases of severe sepsis were identified33,49,87; however, theauthors did not describe the technique used, and someproblems may have occurred because bolus liposuction wasemployed rather than structural fat grafting.

In this review, the rate (3·9 per cent within 12 months inhigher-quality publications) and severity of clinical com-plications after autologous fat grafting were lower thanthose described after breast cosmetic and reconstructionprocedures performed with breast implants and/or myocu-taneous flaps101–113. Some specialists still believe that the



palpable nodularity responsible for most clinical complica-tions could interfere with future breast cancer screening,in addition to causing anxiety among patients.

Similarly, in the 17 articles (2560 patients) used toassess the risk of abnormal radiographic changes, therate was 13·0 per cent after a mean of 12 months, similarto that following other breast surgical procedures52,57.Veber et al.81 compared mammograms obtained before andafter autologous fat grafting to the breast, and observedan improvement in radiological pattern 1 year after theprocedure. They concluded that fat grafting did notcause additional difficulties in differentiating a suspectedradiological change.

Concerning the potential risk of breast cancer,experimental studies in the scientific environment havereported that recently grafted adipocytes and preadipocytes(representing around 10 per cent of fat cells in thelipoaspirate) have carcinogenic potential108–112. The risk isbased on a higher local concentration of oestrogen resultingfrom aromatases derived from adipocytes, and someadipocytokines released from these cells that can stimulateangiogenesis and induce cancer113,114. The theory wasrefuted in a recent systematic review of experimentalstudies on the subject by Lohsiriwat and co-workers113.

Of all the studies included in this review, only threewere designed to assess oncological risk. A prospectivecohort study by Rietjens and colleagues83 with follow-up of 18 months analysed 155 patients treated for breastcancer (191 breasts; 114 total mastectomies, 77 partialmastectomies) and found only one recurrence, whichwas diagnosed shortly after the fat grafting procedure,and considered not relevant. Similarly, Rigotti andco-workers75 compared tumour recurrence in a non-randomized study of patients treated for breast cancer withmodified radical mastectomy and autologous fat graftingfor breast reconstruction. Although five of the 137 patientsdeveloped recurrence, the authors concluded that therewas no higher oncological risk in patients treated withlipofilling than in the control group. Finally, Petit et al.93

conducted a case–control study, in which 321 womentreated by fat grafting were matched and compared with642 women who received similar oncological treatmentduring a mean of 26 months. There were eight localrecurrences in the lipofilling group compared with 19 incontrols, suggesting that fat grafting was not contributory.

In this review the rate of breast cancer recurrence inwomen who had fat grafting to the breast was similar topublished rates for patients undergoing mastectomy whodid not receive fat grafting115–119. At present there isno evidence that fat grafting increases the risk of breast

cancer25,75,83,93, but confirmation of oncological safetyawaits the results of controlled trials.

Acknowledgements

This research was funded by Coordenacao deAperfeicoamento de Pessoal de Nıvel Superior (CAPES),the Brazilian federal institution for post graduation pro-grammes.Disclosure: The authors declare no conflict of interest.

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