Babak J Mehrara

Boston Children's Hospital, Boston, Massachusetts, United States

Are you Babak J Mehrara?

Claim your profile

Publications (231)649.7 Total impact

  • [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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 · 2.33 Impact Factor
  • Plastic &amp Reconstructive Surgery 12/2014; 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
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE Both rates of breast reconstruction and implant use have increased in the last decade (1,2). Despite this trend, it is not uncommon for women to elect autologous reconstruction following successful tissue expander/implant reconstruction. The aim of this study was to determine whether satisfaction and HR-QOL differs following each breast reconstruction procedure for individual conversion patients. METHODS From 1991-2013, 242 patients at a single intuition were identified as conversion patients. The BREAST-Q Reconstruction module consists of independent scales (scores 0-100) that evaluate two domains, 1) Satisfaction: Satisfaction with Breasts, Outcome, Care and 2) HR-QOL: Psychosocial, Sexual, and Physical well-being. Prospectively collected BREAST-Q data was available for n=59 (24.4%) patients at one of three time points (post-tissue expander placement, post-implant placement, post-autologous reconstruction). Twenty-seven patients completed at least one BREAST-Q scale post-tissue expander/implant placement AND post autologous reconstruction. Paired t-tests were conducted for each scale to assess individual change in patient satisfaction and HR-QOL. RESULTS The study sample (n=59) was characterized by a mean age at tissue-expander placement of 48.3 ± 7.5 (34.0–64.0) years; average months between autologous reconstruction and BREAST-Q scale completion of 33.8 ± 32.7 (1.3 –119.3); 52% underwent unilateral reconstruction, and 33.9% did not receive radiotherapy. On paired analysis, between post-TE/implant surgery and post autologous surgery, patients reported a higher mean score for Satisfaction with Breasts (37 v 69, P=0.001), Satisfaction with Outcome (61 v 84, P=0.050), Sexual Well-being (33 v 52, P=0.044) and Physical Well-being (67 v 79, P=0.001). Satisfaction with Care scales (surgeon, information, medical team and office staff) did not differ on individual or group-level analysis following implant and autologous breast reconstruction. CONCLUSIONS Achieving patient satisfaction and improving or maintaining HR-QOL are important outcomes of breast reconstruction surgery. As healthcare resources are under increasing scrutiny, understanding how different techniques of breast reconstruction impact patient satisfaction and HR-QOL is crucial information for patients, clinicians, policy-makers and quality-improvement efforts. This study suggests that patients who have experienced both implant and autologous breast reconstruction report significant improvements in Satisfaction and HR-QOL following autologous reconstruction.
    Plastic &amp Reconstructive Surgery 10/2014; 134(4S-1 Suppl):89. DOI:10.1097/01.prs.0000455437.12637.41 · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: In 2012, 12,533 abdominal flap breast reconstructions were performed in the USA, 63.8% of all autologous breast reconstructions performed.1The purpose of this study was to compare patient-reported satisfaction and quality of life between pedicled and free abdominal flap reconstruction using the BREAST-Q. Methods: Women undergoing post-mastectomy breast reconstruction using pedicled or free abdominal flaps were identified from two prospectively maintained databases at two sites in North America from 2008-2013, and were asked to complete the BREAST-Q post-operatively. BREAST-Q scores were assessed for each domain and compared between pedicled and free abdominal flap patients, with higher scores indicating greater satisfaction/outcome. Results: Of the 171 patients who completed the BREAST-Q, 96 (56.1%) underwent pedicled flap reconstruction and 75 (43.9%) underwent free flap reconstruction. Pedicled patients were older (mean 54.1 years v 51.1, p=0.020), had longer length of time from reconstruction to BREAST-Q completion (mean 47.5 months v 35.9, p=0.000), and were more likely to have unilateral (87.5% v 72.0%, p=0.011) and immediate reconstruction (79.2% v 64.0%, p=0.044). Overall, patients who underwent pedicled flap reconstruction scored significantly higher on the BREAST-Q compared to free flap reconstruction patients in Satisfaction with Breasts (+5.9, p=0.043), Sexual Well-Being (+7.5, p=0.045), and Physical Well-Being Chest (+5.6, p=0.022). There was no significant difference in the Physical Well-Being Abdomen (+3.0, p=0.394) or Satisfaction with Outcome (+2.6, p=0.450) scores. However, when post-operative follow-up time was controlled for to include only patients at ≥36 months post-op (mean 57.8 months for pedicled (N=68 patients) v 56.3 months for free (N=34 patients), p=0.544), there were no significant differences in BREAST-Q scores, including Satisfaction with Breasts (+3.1, p=0.474), Outcome (-2.5, p=0.547), Sexual Well-Being (+0.3, p=0.955), Chest (+3.3, p=0.292), and Abdomen (-1.5, p=0.764). Conclusions: Decision-making in breast reconstruction can be difficult as patients are often offered many options, including pedicled and free abdominal flap reconstruction. In this study, patients who underwent pedicled flap reconstruction had greater initial satisfaction compared to those who underwent free flap reconstruction. However, when post-operative time was controlled for, there were no significant differences between the two. Thus, patients may be equally satisfied with either reconstruction, or rather patient satisfaction equalizes between the two over time. These results can be used to facilitate clinical and patient decision-making in the setting of autologous breast reconstruction.
    Plastic &amp Reconstructive Surgery 10/2014; 134(4S-1 Suppl):88. DOI:10.1097/01.prs.0000455435.05014.77 · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: The lymphatic system is commonly injured during cancer treatment. However, despite the morbidity of these injuries, there are currently no options for replacing damaged lymphatics. The purpose of this study was to optimize methods for decellularization of murine lymph nodes (LN) and to determine if these scaffolds can be used to tissue engineer lymph node-like structures. Methods and Results: LNs were harvested from adult mice and subjected to various decellularization protocols. The degree of decellularization and removal of nuclear material was analyzed histologically and quantitatively using DNA isolation. In addition, we analyzed histological architecture by staining for matrix proteins. After the optimal method of decellularization was identified, decellularized constructs were implanted in the renal capsule of syngeneic or allogeneic recipient mice and analyzed for antigenicity. Finally, to determine if decellularized constructs could deliver lymphocytes to recipient animals, the matrices were repopulated with splenocytes, implanted in submuscular pockets, and harvested 14 days later. Decellularization was best accomplished with the detergent sodium dodecyl sulfate (SDS), resulting in negligible residual cellular material but maintenance of LN architecture. Implantation of decellularized LNs into syngeneic or allogeneic mice did not elicit a significant antigenic response. In addition, repopulation of decellularized LNs with splenocytes resulted in successful in vivo cellular delivery. Conclusions: We show, for the first time, that LNs can be successfully decellularized and that these matrices have preserved extracellular matrix architecture and the potential to deliver leukocytes in vivo. Future studies are needed to determine if tissue engineered lymph nodes maintain immunologic function.
    Lymphatic Research and Biology 08/2014; DOI:10.1089/lrb.2013.0054 · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphedema is a chronic debilitating condition and curative treatment is yet to be found. Tissue engineering approach, which combines cellular components, scaffold, and molecular signals hold great potential in the treatment of secondary lymphedema with the advent of lymphatic graft to reconstruct damaged collecting lymphatic vessel. This review highlights the ideal characteristics of lymphatic graft, the limitation and challenges faced, and the approaches in developing tissue-engineered lymphatic graft.
    Journal of Surgical Research 07/2014; DOI:10.1016/j.jss.2014.07.059 · 2.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphödem ist eine häufige Erkrankung, bei der das Lymph­ system nicht in der Lage ist, interstitielle Flüssigkeit adäquat zu beseitigen. Dabei handelt es sich um eine chronische und progressive Krankheit, die mit einer Akkumulation von Flüssigkeit beginnt, im Laufe der Zeit verändert sich die Pathologie aber zu einer Anreicherung von adipofibrotischem Gewebe. Die Einla­ gerung von Fettgewebe ist ein histologischer und patho­ logischer Schlüsselprozess beim chronischen Lymph­ ödem. Obwohl dieser Prozess dazu führt, dass das Lymphödem auf herkömmliche Behandlungsmethoden wie Manuelle Lymphdrainage und Kompressionsbe­ strumpfung nicht mehr reagiert, ist wenig darüber bekannt, wie die Fetteinlagerung in das Lymphödem reguliert wird. Unsere Forschungsgruppe konnte kürzlich zeigen, dass eine lymphatische Verletzung zu einer Aktivierung von Fettdifferenzierungsgenen führt, was in einer Hypertro­ phie und Proliferation von Adipozyten resultiert (1, 2). Genau genommen haben wir herausgefunden, dass das in einem Lymphödem eingelagerte Fettgewebe histolo­ gisch ähnlich ist zu demjenigen bei einer generalisierten Fettleibigkeit, was durch eine Infiltration chronisch inflammatorischer Zellen sichtbar ist (3, 4). Diese Erkenntnisse deuten darauf hin, dass Adipozyten und der Prozess der Fetteinlagerung eine Rolle in der Pathologie des Lymphödems spielen können. Dieses Konzept wird von der Tatsache unterstützt, dass eine Fetteinlagerung ein Schlüsselregulator einer Vielzahl von Erkrankungs­ prozessen ist. Ein Mechanismus, bei dem das Fettgewebe eine Patholo­ gie moduliert, ist die Entstehung von Wachstumsfaktoren und Zytokinen wie Interleukin­6 (IL­6). In der laufenden Studie haben wir beschlossen, uns auf IL­6 zu fokussie­ ren, weil frühere Studien gezeigt haben, dass die Expres­ sion von IL­6 signifikant erhöht ist bei beiden Tiermo­ dellen für primäre und sekundäre Lymphödeme. Auch ist IL­6 dafür bekannt, bei der Fettgewebe­Homöostase eine kritische Rolle zu spielen (5, 6). Was noch ausführlich beschrieben werden muss ist, wel­ cher Verbindungsmechanismus zwischen Entzündung und Fetthomöostase beim Lymph ödem zugrunde liegt. In dieser Studie möchten wir die Rolle von IL­6 bei der Fetteinla­ gerung im Lymphödem untersu­ chen. Wir fanden heraus, dass klinische Biopsieproben und Serum von Lymphödempatien­ ten signifikant erhöhte IL­6­Werte ebenso im Serum wie auch im ödematösen Gewebe aufwiesen. Diese Expres­ sion von IL­6 war stark assoziiert mit der Fetteinlagerung und Entzündung in unserem Maus­Lymphödem­Modell. Interessanterweise scheint die CD4 +
    Vasomed 07/2014; 26(3):146-149.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The aim of this study was to determine whether sterile inflammatory reactions can serve as a physiologic means of augmenting lymphangiogenesis in transplanted lymph nodes using a murine model. Methods: The authors used their previously reported model of lymph node transfer to study the effect of sterile inflammation on lymphatic regeneration. Mice were divided into three groups: group 1 (controls) underwent lymphadenectomy followed by immediate lymph node transplantation without inflammation; group 2 (inflammation before transfer) underwent transplantation with lymph nodes harvested from donor animals in which a sterile inflammatory reaction was induced in the ipsilateral donor limb; and group 3 (inflammation after transfer) underwent transplantation with lymph nodes and then inflammation was induced in the ipsilateral limb. Lymphatic function, lymphangiogenesis, and lymph node histology were examined 28 days after transplantation and compared with those of normal lymph nodes. Results: Animals that had sterile inflammation after transplantation (group 3) had significantly improved lymphatic function (>2-fold increase) on lymphoscintigraphy, increased perinodal lymphangiogenesis, and functional lymphatics compared with the groups with no inflammation and inflammation before transplantation (p < 0.01). Inflammation after transplantation was associated with a more normal lymph node architecture, expansion of B-cell zones, and decreased percentage of T cells compared with the other experimental groups. Conclusions: Sterile inflammation is a potent method of augmenting lymphatic function and lymphangiogenesis after lymph node transplantation and is associated with maintenance of lymph node architecture. Induction of inflammation after transplantation is the most effective method and promotes maintenance of normal lymph node B- and T-cell architecture.
    Plastic &amp Reconstructive Surgery 07/2014; 134(1):60-68. DOI:10.1097/PRS.0000000000000286 · 3.33 Impact Factor
  • Babak J Mehrara, Arin K Greene
    [Show abstract] [Hide abstract]
    ABSTRACT: Lymphedema is a chronic disorder that, in developed countries, occurs most commonly after lymph node dissection for cancer treatment. Although the pathophysiology of lymphedema is unknown, the disease is characterized histologically by fibrosis and abnormal adipose deposition. Clinical studies have provided evidence that obesity and postoperative weight gain are significant risk factors for the development of lymphedema. In fact, recent studies have shown that extreme obesity can result in markedly impaired lymphatic function and primary lymphedema. The aim of this Special Topic article is to review evidence linking obesity and lymphedema. In addition, the authors review recent studies that have analyzed the cellular mechanisms that may be responsible for this relationship, with a goal of highlighting areas of research that may have significant translational potential.
    Plastic &amp Reconstructive Surgery 07/2014; 134(1):154e-160e. DOI:10.1097/PRS.0000000000000268 · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Although obesity is a major clinical risk factor for lymphedema, the mechanisms that regulate this effect remain unknown. Recent reports have demonstrated that obesity is associated with acquired lymphatic dysfunction. The purpose of this study was to determine how obesity induced lymphatic dysfunction modulates the pathologic effects of lymphatic injury in a mouse model. Methods: We used a diet-induced model of obesity in adult male C57BL/6J mice in which experimental animals are fed a high fat diet and controls are fed a normal chow diet for 8-10 weeks. We then surgically ablated the superficial and deep lymphatics of the mid-portion of the tail. Six weeks postoperatively, we analyzed changes in lymphatic function, adipose deposition, inflammation, and fibrosis. We also compared responses to acute inflammatory stimuli in obese and lean mice. Results: Compared with lean controls, obese mice had baseline decreased lymphatic function. Lymphedema in obese mice further impaired lymphatic function and resulted in increased subcutaneous adipose deposition, increased CD45(+) and CD4(+) cell inflammation (p<0.01), and increased fibrosis, but caused no change in the number of lymphatic vessels. Interestingly, obese mice had a significantly increased acute inflammatory reaction to croton oil application. Conclusions: Obese mice have impaired lymphatic function at baseline that is amplified by lymphatic injury. This effect is associated with increased chronic inflammation, fibrosis, and adipose deposition. These findings suggest that obese patients are at higher risk for lymphedema due to impaired baseline lymphatic clearance and an increased propensity for inflammation in response to injury.
    AJP Heart and Circulatory Physiology 05/2014; 307(2). DOI:10.1152/ajpheart.00244.2014 · 4.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Indications for radiotherapy in breast cancer treatment are expanding. Long-term satisfaction and health-related quality of life (HR-QOL), important outcomes after alloplastic breast reconstruction and radiation, have not been measured in irradiated patients by using a condition-specific, validated patient-reported outcomes instrument. The aim was to evaluate patient satisfaction and HR-QOL in patients with implant breast reconstruction and radiotherapy. A multicenter cross-sectional survey of patients who underwent implant-based breast reconstruction from three centers in the United States and Canada, with and without radiation, was performed. Satisfaction with breasts, satisfaction with outcome, psychosocial well-being, sexual well-being, and physical well-being outcomes were evaluated using the BREAST-Q(©) (Reconstruction Module). Multivariable analysis was performed to evaluate the effect of radiotherapy on patient satisfaction with breasts with adjustment by patient and treatment characteristics. The response rate was 71 %, with 633 completed questionnaires returned. Mean follow-up was 3.3 years for irradiated patients (n = 219) and 3.7 years for nonirradiated patients (n = 414). Patients with radiation had significantly lower satisfaction with breasts (58.3 vs. 64.0; p < 0.01), satisfaction with outcome (66.8 vs. 71.4; p < 0.01), psychosocial well-being (66.7 vs. 70.9; p < 0.01), sexual well-being (47.0 vs. 52.3; p < 0.01), and physical well-being (71.8 vs. 75.1; p < 0.01) compared with nonirradiated patients. Multivariable analysis confirmed the negative effect of radiotherapy on satisfaction with breasts (β = -2.6; p = 0.03) when adjusted for patient and treatment factors. Radiotherapy has a negative effect on HR-QOL and satisfaction with breasts in patients with implant reconstruction compared with nonirradiated patients. The information provided here can inform decision-making and help set appropriate expectations for patients undergoing implant breast reconstruction and radiation.
    Annals of Surgical Oncology 04/2014; 21(7). DOI:10.1245/s10434-014-3483-2 · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Lymphedema (LE) is a morbid disease characterized by chronic limb swelling and adipose deposition. Although it is clear that lymphatic injury is necessary for this pathology, the mechanisms that underlie lymphedema remain unknown. Interleukin-6 (IL-6) is a known regulator of adipose homeostasis in obesity and has been shown to be increased in primary and secondary models of lymphedema. Therefore, the purpose of this study was to determine the role of IL-6 in adipose deposition in lymphedema. Methods: The expression of IL-6 was analyzed in clinical tissue specimens and serum from patients with/without LE, as well as in 2 mouse models of lymphatic injury. In addition, we analyzed IL-6 expression/adipose deposition in mice deficient in CD4(+) cells (CD4K0), IL-6 expression (IL-6KO), or mice treated with a small molecule inhibitor of IL-6 or CD4 depleting antibodies, to determine how IL-6 expression is regulated and the effect of changes in IL-6 expression on adipose deposition after lymphatic injury. Results: Patients with LE and mice treated with lymphatic excision of the tail had significantly elevated tissue and serum expression of IL-6 and its down-stream mediator. The expression of IL-6 was associated with adipose deposition and CD4+ inflammation and was markedly decreased in CD4KO mice. Loss of IL-6 function resulted in significantly increased adipose deposition after tail lymphatic injury. Conclusion: Our findings suggest that IL-6 is increased as a result of adipose deposition and CD4(+) cell inflammation in lymphedema. In addition, our study suggests that IL-6 expression in lymphedema acts to limit adipose accumulation.
    AJP Heart and Circulatory Physiology 03/2014; 306(10). DOI:10.1152/ajpheart.01019.2013 · 4.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent trends in U.S. breast oncology and autologous reconstruction, such as greater use of contralateral prophylactic mastectomies and microsurgery, may have increased reconstructive complication rates and costs. Simultaneously, with the increased complexity of autologous reconstruction in the setting of declining reimbursement, there may be market concentration of these procedures to specialized high-volume centers. This study aimed to (1) measure cost of autologous reconstruction in the setting of microsurgical technique, contralateral prophylactic mastectomies, and high-volume centers; and (2) analyze trends in market share of these procedures. Inflation-adjusted hospital charges were analyzed for autologous procedures using the Nationwide Inpatient Sample database (1998 to 2010), including a subgroup of microsurgical cases. Median charges were adjusted by patient case mix and analyzed by outcome, procedure type, and hospital volume using the Mann-Whitney test. Market share was evaluated through examination of trends in hospitals performing autologous reconstruction and procedures at high-volume centers. Median charges for 21,016 autologous reconstructions were $22,198. Costs were higher for bilateral reconstruction ($34,202) and microsurgical cases ($57,449). Hospital charges increased from $20,315 (no complications) to $42,210 when both surgery-specific and systemic complications were present (p < 0.01). High-volume hospitals reduced charges by 7.5 percent and had lower costs in the setting of complications (p < 0.01). The number of hospitals performing autologous reconstructions decreased 35 percent, with increasing annual procedures in high-volume centers (48.3 to 73.3, p < 0.01). Bilateral reconstructions and microsurgical technique are associated with greater health care costs. The market concentration of autologous reconstruction to high-volume centers is associated with reduced charges. The long-term implications of this trend are unknown.
    Plastic and Reconstructive Surgery 03/2014; 133(3):463-70. DOI:10.1097/PRS.0000000000000039 · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.
    Plastic and Reconstructive Surgery 02/2014; 133(2):301-10. DOI:10.1097/01.prs.0000436840.69752.7e · 3.33 Impact Factor
  • Article: Abstract 45
    Plastic &amp Reconstructive Surgery 01/2014; 133:10-99. DOI:10.1097/01.prs.0000445078.16709.13 · 3.33 Impact Factor
  • Plastic &amp Reconstructive Surgery 01/2014; 133:180. DOI:10.1097/01.prs.0000444992.83055.8d · 3.33 Impact Factor

Publication Stats

5k Citations
649.70 Total Impact Points

Institutions

  • 2014
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2003–2014
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Plastic and Reconstructive Surgical Service
      New York, New York, United States
  • 1999–2013
    • NYU Langone Medical Center
      • Department of Surgery
      New York, New York, United States
  • 2011
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 2008–2011
    • Royal Free London NHS Foundation Trust
      • Department of Plastic and Reconstructive Surgery
      Londinium, England, United Kingdom
    • Louisiana State University Health Sciences Center New Orleans
      New Orleans, Louisiana, United States
    • University of Pittsburgh
      • Department of Plastic and Reconstructive Surgery
      Pittsburgh, PA, United States
    • New York Presbyterian Hospital
      New York City, New York, United States
  • 2000–2011
    • University of California, Los Angeles
      • • Department of Surgery
      • • Division of Plastic Surgery
      Los Angeles, CA, United States
  • 2010
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2009
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2005
    • University of Rochester
      • Division of General Medicine
      Rochester, New York, United States
  • 2001–2002
    • Stanford University
      • Department of Surgery
      Stanford, CA, United States
    • New York University
      • Institute of Reconstructive Plastic Surgery
      New York, New York, United States
  • 1998–2002
    • State University of New York Downstate Medical Center
      • Department of Surgery
      Brooklyn, NY, United States
  • 2000–2001
    • CUNY Graduate Center
      New York, New York, United States
    • Medical College of Wisconsin
      • Department of Plastic Surgery
      Milwaukee, WI, United States
  • 1999–2001
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      New York City, New York, United States
    • University of Connecticut
      • Department of Surgery
      Mansfield City, CT, United States