There remains significant confusion about the relationship between primary lymphedema and lymphatic malformations, which is further complicated by disagreements surrounding the definition of primary lymphedema. However, primary lymphedema is regarded as a clinical manifestation of a lymphatic malformation that developed during the later stage of lymphangiogenesis  . Lymphatic malformations are low flow vascular malformations and can be divided into extra-truncular and truncular forms. The truncular lymphatic malformations are further divided into: primary lymphedema and visceral Forms (those which include lymphangiectasis, lymphangiomatosis). Some truncular and visceral lymphatic malformations have proliferative potential (lymphangiomatosis). Truncular and extra-truncular lymphatic malformations can co-exist (ISSVA Classification International Consensus, 11 Workshop, Rome, 1996).
The majority of the clinical conditions that are considered to be primary lymphedema are due to truncular lymphatic malformation that arise during the final stages of the lymphangiogenesis . when there is the formation of the lymphatic trunks, vessels, and nodes . These malformations result in hypoplasia, hyperplasia, or aplasia of the lymphatic vessels and/or the lymph nodes and may clinically manifest as obstruction or dilatation. When the malformations result in the absence or defectiveness of the endoluminal valves, reflux of lymph is the primary clinical manifestation. In contrast, the extra-truncular lymphatic malformations develop at an earlier stage of the embryogenesis and are associated with immature embryonic tissue that fails to involute, remaining in the earlier embryonic stages .
Some primary or congenital lymphedemas are not true congenital defects but occur due to postnatal destruction of the lymphatic collectors or nodes. These mimic the congenital condition in terms of clinical presentation and are classified as congenital lymphedema because the symptoms are present at birth . Other primary lymphedemas do not have anatomically evident truncular malformations of the lymphatic system but represent a functional defect that is molecular in origin .
Primary lymphedemas have typically been classified into 3 groups, depending on the age of the onset of clinical manifestations: congenital (before age 2 years), praecox (between age 2 and 35 years), and tarda (after age 35 years). However, there is significant criticism of this arbitrary categorization as it is not clinically useful . In addition, the category of primary lymphedema often includes other types of lymphedema of an idiopathic nature without an identifiable etiology (that is, radiation, surgery, or infection). Some experts also believe that all lymphedema and lymphatic malformations are genetically derived and have proposed that lymphedema should be considered as an abnormality of lymph drainage and classified only by the tissue territory drained. We prefer to classify the lymphedemas using an etiological basis, as can be seen in Figure 1.
Figure 1. Etiological classification (C. Campisi, 2001)
In order to provide a comprehensive classification system of lymphedema that encompasses immunohistopathological criteria, level of clinically evident edema, lymphoscintigraphic findings, and level of physical disability, we developed a three stage model (Table 1). In clinical practice, stages IA, IB, IIA and early IIB can be considered as early manifestations of disease and late IIB, IIIA and IIIB stages to be chronic and advanced. It should be noted that lymphedema is a progressive disease and can move rapidly between the stages without adequate treatment.
GENERAL CONSIDERATIONS OF THE SURGICAL TREATMENT OF LYMPHEDEMA
Refractory lymphedema unresponsive to conservative treatment measures may be appropriately managed by surgical means. Indications for surgery include: insufficient volume reduction by appropriate conservative methods (less than 50% reduction), recurrent lymphangitis or erysipelas episodes, intractable pain or discomfort usually associated with the excess swelling and inflammation, loss of limb function and increasing disability, patient dissatisfaction with previous treatment outcomes and willingness to proceed with surgery.
Lymphatic microsurgery represents a means to restore lymphatic drainage by bypassing the obstruction in the lymphatic pathway and directing the flow of lymph into the veins (MLVA) or, in the case of an associated venous pathology, by using an autologous vein graft to bridge the gap in the lymphatic collectors around the obstruction (MLVLA).
The Center of Lymphatic Surgery and Microsurgery in Genoa, Italy, has obtained excellent stable clinical outcomes for over 40 years by utilizing MLVA/MLVLA techniques , . Anastomoses are performed at a single-site using larger lymphatic vessels attached to collateral branches of main veins. Some surgeons using lymphatic microsurgery have adopted other techniques of making multiple incisions distally down the lymphedematous limb and performing a lymphatic-venular anastomosis at each incision. The rationale behind using a single-site technique is two-fold. First, a proximal single-site surgery likely lowers the risk of infection, as there is less surface area for bacteria to breach the skin barrier. Second, pressure differentials between veins and lymphatics are more easily overcome with larger vessels obtained at a single-site .
The retrospective evaluation of over 2600 patients affected by upper and/or lower limb lymphedema, between 1973 and 2013, who underwent lymphatic microsurgery for primary and secondary peripheral lymphedemas is described. Compared to pre-operative conditions, patients obtained significant reductions in excess limb volume of over 84%, with an average follow-up of 10 years or more. Over 86% of patients with earlier stages of disease (stages IB or IIA) progressively stopped using conservative therapies and 42% of patients with later stages (stages IIB and III) decreased the frequency of physical therapies [Figure 2, 10].
Figure 2. Pre- and post-operative photos of patient with lymphedema of the left leg
Primary lymphedema is regarded as a clinical manifestation of a lymphatic malformation that developed during the later stage of lymphangiogenesis, where the crucial symptom is chronic lymph stasis. Lymphatic microsurgery provides a means to restore lymphatic drainage. MLVA and MLVLA techniques when performed at a single-site produce excellent outcomes in the treatment of both primary and secondary lymphedemas, giving the possibility of a complete restoration of lymphatic flow in early stages of disease when tissue changes are minimal.
Table 1. Three-Stage Classification of Lymphedema
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