Fibrosis and secondary lymphedema: chicken or egg?

Kataru, Raghu P.; Wiser, Itay; Baik, Jung Eun; Park, Hyeung Ju; Rehal, Sonia; Shin, Jin Yeon; Mehrara, Babak J.

doi:10.1016/j.trsl.2019.04.001

Cited by 64 publications

(52 citation statements)

References 54 publications

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“…However, chronic inflammation-related fibrosis plays a key role in recent publications. Lymphatic damage is associated with a chronic immune response (T helper cell) that causes fibrosis and lymphatic leakage, decreased lymphatic pumping, and impaired collateral lymphatic formation ( 22 ) .…”

Section: Discussionmentioning

confidence: 99%

Prevelance of upper extremity lymphedema and risk factors in patients with mastectomy: Single-center, observational, cross-sectional study

Koca

Aktaş

Kurtgil

2020

tjod

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Amaç: İn vitro fertilizasyon (İVF) ve embriyonik manipülasyonlar yoluyla gebe kalan kadınlarda hormon kullanımı, pulmoner hipertansiyon olasılığı da dahil olmak üzere yenidoğanların sağlığıyla ilgili endişeleri artırmıştır. Bu nedenle bu çalışma, term İVF yenidoğanlarında pulmoner arter basıncını değerlendirmeyi amaçlamıştır. Gereç ve Yöntemler: Bu prospektif kesitsel çalışma Mart 2013 ile Ekim 2017 arasında gerçekleştirilmiştir ve 160 İVF yenidoğanı (grup 1) 160 doğal yolla olan yenidoğanla (grup 2) karşılaştırmaktadır. Her iki gruptaki yenidoğanlar, gebelik ve yenidoğan yaşı açısından eşleştirilmiş sezaryen ile doğan yenidoğanlardı. Yenidoğanlar üç-yedi günlük idi, 37-39 hafta ve 6 günlük tam dönem gebelik yaşına sahipti ve yenidoğanların doğum ağırlığı normal sınırlarda (2500-4000 g) idi. Sistolik pulmoner arter basıncı (SPAB), triküspit yetersizlik jetinin pik akış hızını temel alan gerçek zamanlı ekokardiyografi kullanılarak tahmin edildi. Bulgular: İki grup arasındaki ortalama SPAB açısından anlamlı bir fark gözlendi (p<0,001). Her ne kadar gestasyonel yaşın SPAB'yi düşürücü etkisi grup 1'de daha fazla ve istatistiksel olarak anlamlı olsa da, doğumdan sonra PAB'de kademeli azalma bu grupta daha yavaş gözlenmiştir. Ayrıca, her iki grupta da gebelik yaşının SPAB'yi düşürücü etkisi yenidoğan yaşına göre daha belirgindi. Ayrıca, her iki grupta da SPAB ile yenidoğan ağırlığı arasında anlamlı bir ters korelasyon gözlendi; ancak bu korelasyonun grup 1'de daha kuvvetli olduğu görüldü. Sonuç: Çalışmamız, İVF'yi yenidoğanlarda pulmoner hipertansiyon insidansında artış ile ilişkili bulmuştur. Bu nedenle, İVF yenidoğanlarında pulmoner

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Section: Discussionmentioning

confidence: 99%

Prevelance of upper extremity lymphedema and risk factors in patients with mastectomy: Single-center, observational, cross-sectional study

Koca

Aktaş

Kurtgil

2020

tjod

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“…Indeed, a recent study showed that fibrosis induced by chronic inflammation plays a key role in the pathophysiology of the later stages of postoperative lymphedema. 46 This reflects the fact that lymphatic injury activates chronic immune responses that promote fibrosis and decrease lymphatic pumping. Attention should therefore be paid to whether the observed tail thickening is mainly caused by impaired lymphatic capillary formation or enhanced fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Endogenous Calcitonin Gene–Related Peptide Deficiency Exacerbates Postoperative Lymphedema by Suppressing Lymphatic Capillary Formation and M2 Macrophage Accumulation

Matsui

Tanaka

Kamiyoshi

et al. 2019

The American Journal of Pathology

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Lymphedema is a chronic condition caused by disruption of lymphatic vessels, which often occurs after invasive surgery. Calcitonin geneerelated peptide (CGRP) is a 37-amino acid peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene (Calca). CGRP was initially identified as a neuropeptide released primarily from sensory nerves and involved in regulating pathophysiological nociceptive pain. However, recent studies have shown CGRP is also released from a variety of other cells and possesses multiple functions. In this study, CGRP knockout (À/À) mice were used to show the actions of endogenous CGRP in postoperative lymphedema. After generating a mouse postoperative tail lymphedema model, the edema was observed to be more severe in CGRP À/À mice than in wild-type mice. Numbers of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1)epositive lymphatic capillaries were decreased and lymphatic capillary formationerelated factors were down-regulated in CGRP À/À mice. In addition, accumulation of M2 but not M1 macrophages was selectively reduced in the edematous tissue of CGRP À/À mice. Selective depletion of M2 macrophages decreased lymphatic capillary formation and worsened lymphedema in wild-type mice but not CGRP À/À mice, where numbers of M2 macrophages were already diminished. These findings suggest that endogenous CGRP acts to ameliorate postoperative lymphedema by enhancing lymphatic capillary formation and that M2 macrophages play critical roles. CGRP may be a useful therapeutic target for the treatment of postoperative lymphedema.

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“…Recent studies have shown that chronic fibrosis plays a key role in the pathophysiology of lymphedema [16,17]. When opening the axilla, one of the goals is to remove the scars/fibrosis completely or as much as possible [3].…”

Section: Axillary Scar Removal and Fat Advancement Flapmentioning

confidence: 99%

Patient-specific surgical options for breast cancer-related lymphedema: technical tips

et al. 2021

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In order to provide a physiological solution for patients with breast cancer-related lymphedema (BCRL), the surgeon must understand where and how the pathology of lymphedema occurred. Based on each patient’s pathology, the treatment plan should be carefully decided and individualized. At the authors’ institution, the treatment plan is made individually based on each patient’s symptoms and relative factors. Most early-stage patients first undergo decongestive therapy and then, depending on the efficacy of the treatment, a surgical approach is suggested. If the patient is indicated for surgery, all the points of lymphatic flow obstruction are carefully examined. Thus a BCRL patient can be considered for lymphaticovenous anastomosis (LVA), a lymph node flap, scar resection, or a combination thereof. LVA targets ectatic superficial collecting lymphatics, which are located within the deep fat layer, and preoperative mapping using ultrasonography is critical. If there is contracture on the axilla, axillary scar removal is indicated to relieve the vein pressure and allow better drainage. Furthermore, removing the scars and reconstructing the fat layer will allow a better chance for the lymphatics to regenerate. After complete removal of scar tissue, a regional fat flap or a superficial circumflex iliac artery perforator flap with lymph node transfer is performed. By deciding the surgical planning for BCRL based on each patient’s pathophysiology, optimal outcomes can be achieved. Depending on each patient’s pathophysiology, LVA, scar removal, vascularized lymph node transfer with a sufficient adipocutaneous flap, and simultaneous breast reconstruction should be planned.

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Fibrosis and secondary lymphedema: chicken or egg?

Cited by 64 publications

References 54 publications

Prevelance of upper extremity lymphedema and risk factors in patients with mastectomy: Single-center, observational, cross-sectional study

Prevelance of upper extremity lymphedema and risk factors in patients with mastectomy: Single-center, observational, cross-sectional study

Endogenous Calcitonin Gene–Related Peptide Deficiency Exacerbates Postoperative Lymphedema by Suppressing Lymphatic Capillary Formation and M2 Macrophage Accumulation

Patient-specific surgical options for breast cancer-related lymphedema: technical tips

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