Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3783_Библиотеки_им_академика_М_И_Перельмана

Lymphedema can occur either as a primary condition or secondary to injury or insults to the lymphatic system. Primary lymphedema presents during infancy, childhood, or adolescence and is caused by genetic mutations that directly or indirectly regulate lymphatic differentiation and function [5]. Less frequently, primary lymphedema can appear after age 35 and is known as lymphedema tarda [2, 6]. Secondary lymphedema is the most common type of lymphedema and develops in response to direct or indirect injury to the lym­phatic system resulting from infectious diseases (lariasis), trauma or cancer surgery, or obesity [2, 7, 8]. Both primary and secondary lymphedemas share similar pathologic fea­tures, including chronic swelling, inammation, adipose deposition, and brosis; however, there is great variability in

Primary lymphedema is often classied based on the patient’s age at presentation. Congenital lymphedema presents within the rst 2 years of life, lymphedema praecox presents at puberty, and lymphedema tarda is diagnosed after age 35years. The phenotype of primary lymphedema varies with age of onset, anatomical location, inheritance patterns, and underlying genetic cause [9].

In Western countries, most patients develop secondary lymphedema after an iatrogenic injury to the lymphatic sys­tem in the course of their cancer treatment. Breast cancer, due to its high prevalence, is the most common cause of secondary lymphedema. Estimates of the rates of lymphedema in breast cancer survivors following axillary lymph node dissection vary widely—ranging from 15% to 50%—due to heteroge­nous methods used for diagnosis and follow-up time [14–16]. However, it is important to note that even minor disruption of the lymphatic system such as sentinel lymph node biopsy can cause lymphedema in 5–7% of patients [17–19]. Lymphedema is also not limited to breast cancer survivors and occurs com­monly following treatment for gynecological/urologic tumors, melanoma, sarcoma, and pelvic tumors [8, 20, 21]. On aver­age, breast cancer-related lymphedema usually develops approximately 8months following surgery, and nearly 80% of patients who will develop the disease do so within the rst 3years following lymphadenectomy [22]. In contrast, lower extremity lymphedema tends to develop more rapidly, usually presenting within 3–4months of surgery [23].

in the limb or mild aching and tightness. ISL Stage I is mild lymphedema with the accumulation of interstitial uid that subsides with compression. The skin is typically soft with no dermal brosis, and pitting edema is present. This is often called the reversible stage since the edema resolves within 24 h with compression. ISL Stage II is moderate lymph­edema characterized by the development of derma brosis. In Stage II, the edema does not subside with elevation or compression. ISL Stage III is severe lymphedema with per­manent limb swelling and trophic skin changes such as fat deposits, acanthosis, and verrucae [25].

Although there is some debate regarding the efcacy or timing of conservative treatments in preventing the develop­ment of lymphedema, early diagnosis and aggressive physi­cal therapy/compression are helpful in most patients and should be instituted as soon as possible [26, 27].

Historically, it was thought that lymphedema was caused by injury to the lymphatic system and the subsequent failure of the lymphatics to regenerate or form collateral pathways that bypass the zone of injury. This hypothesis was supported by invivo studies that showed that growth factors, such as vascu­lar endothelial growth factor (VEGF), promoted lymphatic regeneration with the resolution of lymphedema [28]. However, recent studies have shown that lymphedema is a progressive disease of the entire lymphatic vascular tree rather than an iso­lated injury at the site of lymph node dissection. The patho­physiology of secondary lymphedema is complex and affects different tissue compartments manifesting as chronic inam­mation, brosis, inhibition of collateral lymphatic vessel for­mation, and adipose tissue deposition [29, 30].

Fibrosis is characterized by the excessive deposition of extracellular matrix, eventually leading to tissue and organ dysfunction. In chronic lymphedema, the lymphatic vessels become progressively brosed with proliferation of smooth muscle cells, valvular dysfunction, and collagen deposition eventually obliterating the vessel lumen [30–33]. The dermal capillary lymphatic vessels also become leaky and encased in brous tissue with resultant dilatation of the lumen and formation of “lymphatic lakes.” These changes are respon­sible for interstitial uid backow in the skin and abnormal changes on indocyanine green lymphography [30, 34]. There is also substantial brosis of the skin and adipose tissue as evidenced by increased deposition of type I and type III col­lagen in the papillary and reticular dermis and subcutaneous fat (Fig.3.2) [35, 36].