Babak J Mehrara

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (254)754.66 Total impact

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    ABSTRACT: The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
    Journal of Investigative Dermatology 07/2015; DOI:10.1038/jid.2015.283 · 6.37 Impact Factor
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    ABSTRACT: Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC) proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2) cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4) and interleukin-13 (IL-13) have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.
    Plastic &amp Reconstructive Surgery 06/2015; 135(6):140-141. DOI:10.1097/01.prs.0000465652.62786.ae · 3.33 Impact Factor
  • Article: Abstract 71
    Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):55-56. DOI:10.1097/01.prs.0000465519.85176.cd · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):26-27. DOI:10.1097/01.prs.0000465470.54750.e5 · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):106-107. DOI:10.1097/01.prs.0000465597.12099.1e · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):103-104. DOI:10.1097/01.prs.0000465593.19723.95 · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):106. DOI:10.1097/01.prs.0000465596.04476.e8 · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):109-110. DOI:10.1097/01.prs.0000465602.42594.9b · 3.33 Impact Factor
  • Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):30-31. DOI:10.1097/01.prs.0000465478.30986.61 · 3.33 Impact Factor
  • Article: Abstract 96
    Plastic and Reconstructive Surgery 05/2015; 135(5S Suppl):71. DOI:10.1097/01.prs.0000465544.96851.0e · 3.33 Impact Factor
  • Katie E Weichman · Leo Urbinelli · Joseph J Disa · Babak J Mehrara
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    ABSTRACT: Breast reduction in patients with a history of lumpectomy and irradiation is controversial because of a heightened risk of infection and wound healing complications. Persistent macromastia or asymmetry remains a problem in this patient population that is commonly not addressed. The authors studied the safety and efficacy of a central mound technique with minimal dissection for breast reduction or mastopexy in patients with a history of breast irradiation. A case-control study of all patients undergoing bilateral breast reduction mammaplasty between 2008 and 2013 at Memorial Sloan Kettering Cancer Center was conducted. Patients who had unilateral breast irradiation and bilateral reduction using the central mound technique were included. Each patient had a control breast and an irradiated breast. Complications and outcomes were analyzed. Thirteen patients were included for analysis. Their average age was 50.23 ± 9.9 years, and average time from irradiation to breast reduction mammaplasty was 41.3 ± 48.5 months (range, 9 to 132 months). The average specimen weight of irradiated breasts was less than that of control breasts; however, this failed to reach statistical significance (254.2 ± 173.5 g versus 386.9 ± 218.5 g; p = 0.099). One patient developed fat necrosis in the previously irradiated breast and underwent biopsy. There was no incidence of nipple necrosis or breast cancer in either irradiated or nonirradiated breasts. Breast reduction mammaplasty in patients who have had irradiation is feasible and can be performed safely in select cases. The central mound technique provides reliable and reproducible results and should be considered in patients with macromastia/asymmetry and a history of irradiation. Therapeutic, III.
    Plastic and Reconstructive Surgery 05/2015; 135(5):1276-1282. DOI:10.1097/PRS.0000000000001147 · 3.33 Impact Factor
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    ABSTRACT: Lower extremity reconstruction following resection of long bone tumors is challenging because of the unique functional demands and growth potential of the lower extremity in children. The use of a free fibula flap inside a massive bone allograft provides a reliable reconstructive option. The authors evaluate the surgical and functional outcomes of using this technique. This is a retrospective review of 12 consecutive patients who underwent reconstruction of segmental femur or tibia defects using a free fibula flap inside a massive bone allograft from 2003 to 2011. Complications and functional outcomes are reported. Twelve patients with a mean age of 15.8 years (range 3 to 49 years) were included in the study. Eight femur defects and four tibia defects were reconstructed. The mean follow up time was 41.4 months. Two constructs were removed because of infection, three patients required bone grafting for nonunion, one patient required an additional operation to excise a skin paddle, and one patient experienced a lower extremity DVT. The mean time to achieve full weight bearing was 14.3 months. The use of a free fibula flap inside a massive bone allograft following bone tumor resection provides an option for lower extremity reconstruction. The allograft component increases the initial strength of the reconstruction while the vascularized fibula component is thought to increase the biologic potential for osteosynthesis and ultimately provide a potentially life-long durable reconstruction. Patients who achieve oncologic control are likely to enjoy a high functional long-term outcome. IV.
    Plastic and Reconstructive Surgery 04/2015; DOI:10.1097/PRS.0000000000001463 · 3.33 Impact Factor
  • Babak J Mehrara
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    ABSTRACT: Introduction: Lymphedema, a common complication of cancer treatment, is characterized by inflammation, fibrosis, and adipose deposition. We previously have shown that macrophage infiltration is increased in mouse models of lymphedema. Because macrophages are regulators of lymphangiogenesis and fibrosis, this study aimed to determine the role of these cells in lymphedema using depletion experiments. Methods: Matched biopsy specimens of normal and lymphedema tissues were obtained from patients with unilateral upper extremity breast cancer-related lymphedema and macrophage accumulation was assessed using immunohistochemistry. In addition, we used a mouse tail model of lymphedema to quantify macrophage accumulation and analyze outcomes of conditional macrophage depletion. Results: Histological analysis of clinical lymphedema biopsies revealed significantly increased macrophage infiltration. Similarly, in the mouse tail model, lymphatic injury increased the number of macrophages and favored M2 differentiation. Chronic macrophage depletion using lethally irradiated wild-type mice reconstituted with CD11b-DTR mouse bone marrow did not decrease swelling, adipose deposition, or overall inflammation. Macrophage depletion after lymphedema had become established significantly increased fibrosis, accumulation of CD4+ cells, and promoted Th2 differentiation while decreasing lymphatic transport capacity and VEGF-C expression. Conclusion: Our findings suggest that macrophages home to lymphedematous tissues and differentiate into the M2 phenotype. In addition, our findings suggest that macrophages have an anti-fibrotic role in lymphedema and either directly or indirectly regulate CD4+ cell accumulation and Th2 differentiation. Finally our findings suggest that lymphedema associated macrophages are a major source of VEGF-C and that impaired macrophage responses after lymphatic injury results in decreased lymphatic function. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 02/2015; 308(9):ajpheart.00598.2014. DOI:10.1152/ajpheart.00598.2014 · 4.01 Impact Factor
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    ABSTRACT: To decrease the rate of infectious complications, surgeons have begun to use Biopatch (Ethicon, Somerville, N.J.) disks at drain exit sites. The authors investigated whether use of a Biopatch disk could convey a reduction in perioperative infections in patients undergoing immediate tissue expander breast reconstruction. A retrospective review was conducted of all patients undergoing tissue expander/implant breast reconstruction from November of 2010 to November of 2012 at a single institution. Breasts were divided into two cohorts: controls with traditional adhesive dressings and those with Biopatch disks at drain sites. Breasts were compared based on demographics, complications, drain duration, and antibiotic type. A total of 1211 breasts met inclusion criteria. The control group (November of 2010 to October of 2011) included 606 breasts. The Biopatch cohort (November of 2011 to October of 2012) included 605 breasts. When comparing breasts with disks to controls, there were no statistical differences in overall infection (6.2 versus 7.4 percent; p = 0.4235), major infection (4.0 versus 4.3 percent; p = 0.8853), need for explantation (2.2 versus 1.8 percent; p = 0.5372), and mastectomy skin flap necrosis (12.6 versus 14.6 percent; p = 0.3148). However, age greater than 50 years, diabetes mellitus, hypertension, hypercholesterolemia, obesity, history of prior breast irradiation, and mastectomy skin flap necrosis were independent predictors of infectious complications. Biopatch disks do not reduce the rate infectious complications in patients undergoing immediate tissue expander breast reconstruction. Other conventional risks, including medical comorbidities, obesity, and mastectomy skin flap necrosis, remain significantly associated with infectious complications. Therapeutic, III.
    Plastic &amp Reconstructive Surgery 01/2015; 135(1):9e-17e. DOI:10.1097/PRS.0000000000000810 · 3.33 Impact Factor
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    ABSTRACT: Abstract Introduction: Recent advances in microsurgery such as lymphaticovenous bypass (LVB) have been shown to decrease limb volumes and improve subjective symptoms in patients with lymphedema. However, to date, it remains unknown if these procedures can reverse the pathological tissue changes associated with lymphedema. Therefore, the purpose of this study was to analyze skin tissue changes in patients before and after LVB. Methods and Results: Matched skin biopsy samples were collected from normal and lymphedematous limbs of 6 patients with unilateral breast cancer-related upper extremity lymphedema before and 6 months after LVB. Biopsy specimens were fixed and analyzed for inflammation, fibrosis, hyperkeratosis, and lymphangiogenesis. Six months following LVB, 83% of patients had symptomatic improvement in their lymphedema. Histological analysis at this time demonstrated a significant decrease in tissue CD4(+) cell inflammation in lymphedematous limb (but not normal limb) biopsies (p<0.01). These changes were associated with significantly decreased tissue fibrosis as demonstrated by decreased collagen type I deposition and TGF-β1 expression (all p<0.01). In addition, we found a significant decrease in epidermal thickness, decreased numbers of proliferating basal keratinocytes, and decreased number of LYVE-1(+) lymphatic vessels in lymphedematous limbs after LVB. Conclusions: We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps to improve pathologic changes in the skin. These findings suggest that the some of the pathologic changes of lymphedema are reversible and may be related to lymphatic fluid stasis.
    Lymphatic Research and Biology 12/2014; 13(1). DOI:10.1089/lrb.2014.0022 · 1.66 Impact Factor
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    ABSTRACT: Background: Reimbursement has been recognized as a physician barrier to autologous reconstruction. Autologous reconstructions are more expensive than prosthetic reconstructions, but provide greater health-related quality of life. The authors’ hypothesis is that autologous tissue reconstructions are cost-effective compared with prosthetic techniques when considering health-related quality of life and patient satisfaction. Methods: A cost-effectiveness analysis from the payer perspective, including patient input, was performed for unilateral and bilateral reconstructions with deep inferior epigastric perforator (DIEP) flaps and implants. The effectiveness measure was derived using the BREAST-Q and interpreted as the cost for obtaining 1 year of perfect breast health-related quality-adjusted life-year. Costs were obtained from the 2010 Nationwide Inpatient Sample. The incremental cost-effectiveness ratio was generated. A sensitivity analysis for age and stage at diagnosis was performed. Results: BREAST-Q scores from 309 patients with implants and 217 DIEP flap reconstructions were included. The additional cost for obtaining 1 year of perfect breast-related health for a unilateral DIEP flap compared with implant reconstruction was $11,941. For bilateral DIEP flaps compared with implant reconstructions, the cost for an additional breast health-related quality-adjusted life-year was $28,017. The sensitivity analysis demonstrated that the cost for an additional breast health-related quality-adjusted life-year for DIEP flaps compared with implants was less for younger patients and earlier stage breast cancer. Conclusions: DIEP flaps are cost-effective compared with implants, especially for unilateral reconstructions. Cost-effectiveness of autologous techniques is maximized in women with longer life expectancy. Patient-reported outcomes findings can be incorporated into cost-effectiveness analyses to demonstrate the relative value of reconstructive procedures.
    Plastic &amp Reconstructive Surgery 12/2014; 135(4). DOI:10.1097/PRS.0000000000001134 · 3.33 Impact Factor
  • Lisa F Schneider · Babak J Mehrara
    Journal of the American College of Surgeons 12/2014; 220(3). DOI:10.1016/j.jamcollsurg.2014.12.004 · 4.45 Impact Factor
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    ABSTRACT: Background Over the past decade there has been a rise in US breast reconstruction rates with a greater expansion in prosthetic based techniques relative to autologous transfer. Immediate reconstruction in high-risk oncologic and surgical patients may be a contributing factor to these trends. Study Design The National Cancer Data Base from the American College of Surgeons and the American Cancer Society was used to identify a breast cancer cohort(1998-2011) treated with mastectomy. The patients were divided into high and low-risk based on presence or absence of historical surgical or oncologic relative contraindications. Reconstructions were categorized as either autologous or implants. To understand trends for each high-risk characteristic, rates were adjusted by 1000 total mastectomies performed for patients within each specific group and analyzed with Poisson regression. Results Information from 1,040,088 patients with mastectomy was included. Rates of high risk features did not change from 1998-2011. The increase in immediate reconstruction rates was greater for high than low-risk patients(IRR 1.09 versus 1.06, p<.05 for both). There was a greater rate increase in implant than autologous reconstructions for both high and low-risk groups. For high risk patients, implant use increased for all features but with the greatest change for elderly, comorbidities, and post-mastectomy radiotherapy(p<.01). For high risk patients autologous tissue use increased significantly for all features except premastectomy radiotherapy. Conclusions Breast reconstruction increased in high-risk surgical and oncologic patients, suggestive of a diminishing set of relative contraindications. Increased implant use in high-risk patients may be a contributing factor towards the preferential national expansion of prosthetic techniques.
    Journal of the American College of Surgeons 10/2014; 219(4). DOI:10.1097/PRS.0000000000000478 · 4.45 Impact Factor
  • Journal of the American College of Surgeons 10/2014; 219(4):e31. DOI:10.1016/j.jamcollsurg.2014.07.467 · 4.45 Impact Factor

Publication Stats

5k Citations
754.66 Total Impact Points

Institutions

  • 2003–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Plastic and Reconstructive Surgical Service
      • • Department of Surgery
      New York, New York, United States
  • 2011
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 2010
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2009
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2008
    • Louisiana State University Health Sciences Center New Orleans
      New Orleans, Louisiana, United States
    • New York Presbyterian Hospital
      New York City, New York, United States
  • 2000–2006
    • University of California, Los Angeles
      • • Department of Surgery
      • • Division of Plastic Surgery
      Los Angeles, California, United States
    • Medical College of Wisconsin
      • Department of Plastic Surgery
      Milwaukee, Wisconsin, United States
  • 2005
    • University of Rochester
      • Division of General Medicine
      Rochester, New York, United States
  • 2000–2001
    • CUNY Graduate Center
      New York, New York, United States
  • 1999–2001
    • University of Connecticut
      • Department of Surgery
      Mansfield City, CT, United States
    • Stanford University
      • • Department of Surgery
      • • Division of Plastic and Reconstructive Surgery
      Palo Alto, California, United States
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      New York City, New York, United States
  • 1998–1999
    • NYU Langone Medical Center
      • Department of Surgery
      New York, New York, United States