LETTERS AND INVITED COMMENTARY A Classification System for Fat Necrosis in Autologous Breast Reconstruction To the Editor: e read with great interest the recent article of Wagner et al1 describing a new classification system for fat necrosis in autologous breast reconstruction. The authors hypothesized that a classification system for fat necrosis would detect a higher grade of fat necrosis in pedicled f laps as compared with free f laps. To validate the new grading system, it was applied to 2 different cohorts of patients. One group consists of 69 patients receiving a pedicled transverse rectus abdominis myocutaneous, and the other group consists of 69 patients receiving perforator flaps for immediate or delayed autologous breast reconstruction. Reviewing the medical records of these patients, the authors focus their interest especially on type and timing of breast reconstruction, on tobacco and radiation history, as well as on clinical and radiologic signs of fat necrosis and confirm their hypothesis that fat necrosis occurs more often in pedicled flaps as compared with free flaps. They also recommend a treatment algorithm for every group of their classification system. We would like to comment on some issues raised. First of all, the authors point out that, to date, no classification system exists to describe fat necrosis. This is confusing because Russo and Taghian2 describe 5 fat necrosis toxicity scales in their review article. The authors also do not mention on which literature or experience they base their controversial discussed hypothesis. Tan et al3 could not elaborate a significant difference in developing fat necrosis either in pedicled or in free f laps in autologous breast reconstruction, whereas Garvey et al4 confirm the hypothesis. Unfortunately, the authors fail to report whereon the decision to use either pedicled transverse rectus abdominis myocutaneous or perforated f lap technique was dependent. Factors inf luencing the choice of the best reconstructive option are well described in the current literature and should be taken into consideration. These factors include clinicopathologic factors (ie, stage of breast cancer), status of the axillary lymph node, anatomical considerations (ie, obesity, diastasis recti, thin patients with small breasts), extensive abdominal scars, previous radiation therapy, neoadjuvant or adjuvant chemotherapy, and intraoperative technical details.4,5 Damen et al6 presented an algorithm for f lap selection according to the size and the number of perforators.

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It is known that smoking, body mass index of greater than 30 kg/m2, postoperative radiotherapy, and ischemic time are risk factors of the development of fat necrosis in autologous breast reconstruction.7,8 The authors did not consider these correlations in their analysis of the results. Considering the fact that little is known about the pace of growth of fat necrosis, it would have been helpful if the authors mentioned their period of observation. It is reported that the time to diagnosis of fat necrosis ranges from 7.5 to 66 months, with a mean time of 30.7 months.9,10 In this context and besides the described radiologic imaging findings, the authors should also discuss further the inf luencing factors of the development of fat necrosis such as radiation type, volume of tissue receiving different fractional doses, seroma formation, use of hormone therapy, and development of infection.2 Clarke et al11 were the first who reported, in 1983, fat necrosis after breast conservation therapy and described 4 of 8 patients developing fat necrosis at approximately 2 to 23 months after treatment. The chronological correlation of radiation therapy and surgery especially is not pointed out in the current article. Furthermore, radiation before and after reconstruction was combined in 1 group. Because of the substantial variation in the scoring of fat necrosis across studies, we support the need for a universal scoring system to be adopted and implemented for future research on this topic. The practice of autologous breast augmentation will increase considering the newest studies on prosthetic breast augmentation and its complications.12 Thus, a standardized observation and treatment algorithm will be helpful.

So¨ren Ko¨nneker, MD Peter M. Vogt, MD, PhD Andreas Jokuszies, MD Department of Plastic Hand and Reconstructive Surgery Hannover Medical School Hannover, Germany REFERENCES 1. Wagner IJ, Tong WM, Halvorson EG. A classification system for fat necrosis in autologous breast reconstruction. Ann Plast Surg. 2013;70:553Y556. 2. Russo AL, Taghian AG. Fat necrosis of the breast in the accelerated partial breast irradiation era: the need for a universal grading system. Breast Cancer Res Treat. 2013;140:1Y11. 3. Tan S, Lim J, Yek J, et al. The deep inferior epigastric perforator and pedicled transverse rectus abdominis myocutaneous flap in breast reconstruction: a comparative study. Arch Plast Surg. 2013;40:187Y191.

4. Garvey PB, Buchel EW, Pockaj BA, et al. DIEP and pedicled TRAM flaps: a comparison of outcomes. Plast Reconstr Surg. 2006;117:1711Y1719. 5. Kronowitz SJ, Kuerer HM. Advances and surgical decision-making for breast reconstruction. Cancer. 2006;107:893Y907. 6. Damen TH, Morritt AN, Zhong T, et al. Improving outcomes in microsurgical breast reconstruction: lessons learnt from 406 consecutive DIEP/TRAM flaps performed by a single surgeon. J Plast Reconstr Aesthet Surg. 2013;66:1032Y1038. 7. Albino FP, Koltz PF, Ling MN, et al. Irradiated autologous breast reconstructions: effects of patient factors and treatment variables. Plast Reconstr Surg. 2010;126:12Y16. 8. Lee KT, Lee JE, Nam SJ, et al. Ischemic time and fat necrosis in breast reconstruction with a free deep inferior epigastric perforator flap. J Plast Reconstr Aesthet Surg. 2013;66:174Y181. 9. Chen PY, Vicini FA, Benitez P, et al. Long-term cosmetic results and toxicity after accelerated partial-breast irradiation: a method of radiation delivery by interstitial brachytherapy for the treatment of early-stage breast carcinoma. Cancer. 2006; 106:991Y999. 10. Wazer DE, Lowther D, Boyle T, et al. Clinically evident fat necrosis in women treated with high-doseY rate brachytherapy alone for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2001;50:107Y111. 11. Clarke D, Curtis JL, Martinez A, et al. Fat necrosis of the breast simulating recurrent carcinoma after primary radiotherapy in the management of early stage breast carcinoma. Cancer. 1983;52:442Y445. 12. Quaba O, Quaba A. PIP silicone breast implants: rupture rates based on the explantation of 676 implants in a single surgeon series. J Plast Reconstr Aesthet Surg. 2013;66:1182Y1187.

Lipotransfer: The Potential From Bench to Bedside To the Editor: ipotransfer continues to be one of the most frequently performed aesthetic surgical procedures in recent years. The review of Tocco et al1 summarized the potential of lipotransfer from bench to bedside. Recent bench approaches have been proposed to improve the efficacy of lipotransfer; on the other hand, the safety issues of fat grafting are also important issues which were not included in the review of Tocco et al. As plastic surgeons, we have performed lipotransfer since 1997 and we would like to share our opinions on this topic. First, the complications of fat grafting including liquefaction, necrosis caused by insufficient blood supply, were not totally solved. There were many retrospective researches that

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Conflicts of interest and sources of funding: none declared. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved ISSN: 0148-7043/15/7402-0269 DOI: 10.1097/SAP.0000000000000303

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implied liponecrotic cysts, nodules, or calcifications occurrence during follow-up.2,3 All these complications were high risks for patients; meanwhile, the nodules or calcifications might also disturb the diagnosis of breast tumor. Second, adipose-derived stem cellsY enriched fat grafts might be important progress in lipotransfer because the efficacy of the procedure was increased, but in experimental study, it was found that mesenchymal stem cells within tumor stroma promote cancer metastasis which brought patients large safety problems.4,5 Although there was no randomized controlled trial studies for relationships between stem cells treatment and tumorigenesis, it still needs to be cautious with stem cellsYassisted lipotransfer. Lipotransfer is still in the stage of technical evolution. For scientists, the biological behavior of fat after lipotransfer still needs to be clarified, and for surgeons, the safety issues should be given the same importance as efficacy issues for fat grafting. We hope that with more study on the lipotransfer from bench to bedside, more progresses would be made. Chen Cheng, MD Danning Zheng, MD Yun Xie, MD Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai, People’s Republic of China

Qingfeng Li, MD, PhD Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai, People’s Republic of China [email protected]

REFERENCES 1. Tocco I, Widgerow AD, Lalezari S, et al. Lipotransfer: the potential from bench to bedside. Ann Plast Surg. 2014;72:599Y609. 2. 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;61:792Y798. 3. Coleman SR, Saboeiro AP. Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg. 2007;119:775Y785; discussion 786Y777. 4. Eterno V, Zambelli A, Pavesi L, et al. Adiposederived mesenchymal stem cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling. Oncotarget. 2014;5:613Y633. 5. Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557Y563.

Lipotransfer: The Potential From Bench to Bedside: Reply

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e appreciate the letter by Tocco et al regarding complications of fat grafting.

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We agree wholeheartedly with the sentiments of caution expressed particularly relating to postcancer breast reconstruction. In light of this letter pertaining to our referenced review paper, we would add the following comments related to lipotransfer complications. The 2 concerns with fat grafting to the breast relate to interference with breast screening and the possible stimulation of growth of breast cancer cells. The breast cancer screening concern relates to the possible impact of microcalcification, oil cyst formation, and fat necrosis changes evident on mammography. However, more recent publications conducted by various researchers in multicenter studies appear to demonstrate that the changes did not impair breast cancer screening and radiologic follow-up even after breast-conserving surgery.1Y3 The ASPS in their 2012 postmastectomy fat graft guidelines offer the following advice ‘‘When reviewed by experienced radiologists, the presence of oil cysts and fat necrosis on mammography, ultrasound and MRI imaging is distinguishable from suspicious lesions. Surveillance should continue to be rigorous and it is encouraged that radiologists who are experienced in breast imaging work with plastic surgeons to facilitate imaging accuracy.’’4 Additionally, as harvesting and grafting techniques discussed in the review improve, screening of patients for breast cancer should not be adversely affected. As far as the oncologic safety of fat transfer is concerned, definitive recommendations are less apparent and we are in agreement with Tocco et al. Although, as noted and referenced by ASPS,4 evidence suggests that in postmastectomy breast reconstruction patients, fat grafting does not increase the risk of breast cancer recurrence, recent publications have highlighted potential problems with stem cells and breast cancer cells. This concern particularly relates to the fat transfer enriched with adipose-derived stem cells (ADSCs), which may provide stromal support, cytokines, and growth factor delivery facilitating cancer cell growth and promotion of metastases.5,6 It seems that ADSCs may enhance the growth of active cells but not resting dormant cells; in practical terms, there has been no increase in breast cancer observed in many autologous (and enriched) fat reconstructed cases.7 Thus, current recommendations are that reconstructive therapy using ADSC or stromal vascular fraction-enriched fat should be postponed until Received May 20, 2014, and accepted for publication, after revision, June 5, 2014. Conflicts of interest and sources of funding: none declared. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved ISSN: 0148-7043/15/7402-0270 DOI: 10.1097/SAP.0000000000000304

& Volume 74, Number 2, February 2015

there is no evidence of active disease for a period of years7 or until such time that definitive studies allow us to make more informed decisions. We thank the authors for their comments and the publishers for the opportunity to respond. Alan David Widgerow, MBBCh, FACS MMed, FCS (SA Plast) Plastic Surgery Department Center for Tissue Engineering University of California Irvine, CA [email protected]

Ilaria Tocco-Tussardi, MD Plastic Surgery Department Center for Tissue Engineering University of California Irvine, CA

REFERENCES 1. Petit JY, Lohsiriwat V, Clough KB, et al. The oncologic outcome and immediate surgical complications of lipofilling in breast cancer patients: a multicenter studyVMilan-Paris-Lyon experience of 646 lipofilling procedures. Plast Reconstr Surg. 2011;128:341Y346. 2. Philips BJ, Marra KG, Rubin JP. Healing of grafted adipose tissue: current clinical applications of adipose-derived stem cells for breast and face reconstruction. Wound Repair Regen. 2014;22:11Y13. 3. Brenelli F, Rietjens M, De Lorenzi F, et al. Oncological safety of autologous fat grafting after breast conservative treatment: a prospective evaluation. Breast J. 2014;20:159Y165. 4. http://www.plasticsurgery.org/Documents/medicalprofessionals/health-policy/guiding-principles/2012PostMastectomyFatGraft-FatTransferASPSGuidingPrinciples. pdf. Accessed July 01, 2014. 5. Scioli MG, Cervelli V, Gentile P, et al. Human adipose tissue-derived stem cells in breast reconstruction following surgery for cancer: a controversial issue. Stem Cell Discovery. 2013;03:164Y166. 6. Rowan BG, Gimble JM, Sheng M, et al. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS One. 2014;9:e89595. 7. Zimmerlin L, Donnenberg AD, Rubin JP, et al. Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue Eng Part A. 2011;17:93Y106.

Outcomes of Immediate Tissue Expander Breast Reconstruction Followed by Reconstruction of Choice in the Setting of Postmastectomy Radiation Therapy To the Editor: irsch and coworkers1 have recently published on the Annals of Plastic Surgery an interesting paper entitled ‘‘Outcomes of

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* 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Lipotransfer: the potential from bench to bedside.

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