Key Points
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Lymphedema staging
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Surgical treatment of lymphedema & lymphatic microsurgery
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SS-MLVA/single site – multiple lymphatic-venous anastomoses
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MLVLA – multiple lymphatic-venous-lymphatic anastomoses (autologous interpositioned vein graft)
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CLyFT – complete lymphedema functional treatment
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FLLA-LVSP/fibro-lipo-lymph-aspiration by lymph vessel sparing procedure
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BPV test – blue patent violet lymphochromic test
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ICG test – indocyanine green (fluorescent) lymphography (ICGL)
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Superficial and deep lymphoscintigraphy with transport index
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LyMPHA – lymphatic microsurgical preventive healing approach
Current Concepts of Peripheral Lymphedema
Chronic peripheral lymphedema is progressive and relatively painless swelling of any peripheral tissue, including the limbs, head and neck, breast, trunk, or genitals, that is the result of a reduced transport capacity of the lymphatic system. Chronic lymphedema can be classified as primary or secondary, according to the etiology. In patients with secondary lymphedema, a specific external cause (filariasis, previous surgery, radiation, malignancy, infection or inflammation, trauma, etc.) can be identified and is believed to impact on a presumed previously normally functioning lymphatic system by causing an obstruction in the lymphatic flow (either from the direct removal of lymph nodes and/or lymphatic vessels or damage to the same).
The majority of the clinical conditions that are considered to be primary lymphedema are due to truncular lymphatic malformations that arise during the final stages of the lymphangiogenesis, when there is the development of 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 of the lymphatic vessels. In reality, it is not possible to determine if a peripheral lymphedema is primary or secondary simply from a physical or instrumental examination of the affected limb, as the clinical picture is the same regardless of etiology. What is useful, however, is to classify the lymphedema by stage of disease, as this predicts treatment outcome.
In order to provide such 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 21.1 ). In clinical practice, stages IA, IB, IIA, and IIB can be considered as early manifestations of the disease, and stages IIIA and IIIB (properly known as elephantiasis), as chronic and advanced. It should be noted that lymphedema is a progressive disease and, without adequate treatment, can move rapidly between the stages.
| Stage I | A. Latent lymphedema, without clinical evidence of edema, but with impaired lymph transport capacity (provable by lymphoscintigraphy) and with initial immunohistochemical alterations of lymph nodes, lymph vessels, and extracellular matrix. |
| B. Initial lymphedema, totally or partially decreasing by rest and draining position, with worsening impairment of lymph transport capacity and of immunohistochemical alterations of lymph collectors, nodes, and extracellular matrix. | |
| Stage II | A. Increasing lymphedema, with vanishing lymph transport capacity, relapsing lymphangitic attacks, fibroindurative skin changes, and developing disability. |
| B. Column-shaped limb fibrolymphedema, with lymphostatic skin changes, suppressed lymph transport capacity, and worsening disability. | |
| Stage III | A. Properly called elephantiasis, with scleroindurative pachydermitis, papillomatous lymphostatic verrucosis, no lymph transport capacity, and life-threatening disability. |
| B. Extreme elephantiasis with total disability. |
The development, within the last 50 years, of newer surgical techniques to restore lymphatic flow in patients with lymphedema offers a treatment that targets more than symptomatic relief but provides a functional repair of the underlying problem of lymph-stasis. Initial surgical methods were ablative and employed in the advanced stages of disease, with significant levels of fibrotic tissue. However, these were often characterized by significant scarring, poor wound healing, and infection and have largely been abandoned as microsurgical techniques gained popularity.
Initial microsurgical procedures involved lymph nodal-venous shunts, but these had a high failure rate due to the thrombogenic effect of the lymph node pulp entering the venous system and re-endothelization of the lymph node surface. Subsequent approaches involved anastomosing lymphatic vessels directly to collateral veins (lymphatic-venous anastomoses [LVAs]) or to venular vessels (lymphatic-venular anastomoses; supermicrosurgery). These modifications improved the long-term outcome of lymphatic microsurgery, but the efficacy, in terms of volume reduction and long-term stability, remains highly variable between surgical centers worldwide.
The Center of Lymphatic Surgery and Microsurgery in Genoa, Italy, has obtained excellent stable clinical outcomes for over 40 years by utilizing multiple lymphatic-venous anastomoses (MLVA)/multiple lymphatic-venous-lymphatic anastomoses (MLVLA) techniques. Anastomoses are performed at a single surgical site using larger lymphatic vessels attached to collateral branches of the main veins close to vein valves to avoid backflow of blood and the closure of the anastomosis. A single-site approach also minimizes the number of incisions and, thereby, potential entry sites for infection. The retrospective evaluation of this considerable surgical experience is described with reference to the treatment of both primary and secondary peripheral lymphedema.
Patient Selection
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 (<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. Relative contraindications to lymphatic microsurgery are few but include lymphatic-lymph nodal aplasia (exceedingly rare), diffuse metastatic carcinomas, and extremely advanced lymphedema (stage IIIB) unresponsive to conservative measures.
Preoperative Management
Diagnosis
Diagnosis of lymphedema and other lymphatic disorders should be performed by clinicians and lymphologists experienced in this area. The essential diagnostic criteria is evidence of slow, reduced, or completely absent lymphatic flow in the tissue of the limb or body region affected by swelling. Lymphoscintigraphy is generally considered to be the gold standard procedure for measuring this flow, although procedures have yet to be standardized. In Genoa, Italy, lymphoscintigraphy, performed with either 99m Tc-labeled antimony sulfur colloid or 99m Tc-nanocolloid human serum albumin (90% of the particles >80 nm in size) is employed in the diagnostic workup prior to surgery to determine eligibility for derivative MLVA. Lymphoscintigraphy clearly indicates whether the edema is of lymphatic origin in the patients and provides useful data about the etiology and pathohistological nature of the lymphedema. A transport index (TI) is calculated to categorize the lymphatic flow in both the superficial and deep lymphatic vessels as normal or pathological. A score lower than 10 signifies a normal TI, and a score equal to or higher than 10 signifies a pathological TI. Scores are made bilaterally, even in the cases of unilateral swelling.
Our recent research studying the lymphoscintigraphic examinations of 248 patients with limb swelling has demonstrated that, predominantly, the deep subfascial lymphatic vessels are affected (either alone or in combination with the superficial vessels) in patients with primary or secondary upper or lower limb lymphedema. This underlines the importance of performing a lymphoscintigraphy that also includes the study of the deep lymphatic vessels, as there is a group of patients with only deep vessel impairment who would erroneously not receive a diagnosis of lymphedema with a traditional lymphoscintigraphy studying only the superficial vessels.
Recently, there has been a rise of new imaging technologies (including indocyanine green lymphography [ICGL] and lymphatic magnetic resonance imaging), which, while not yet entirely standardized may be useful to help qualitatively delineate lymph flow through vessels and nodes. ICGL is a useful tool for surgical planning and intraoperatively, as it allows for real-time viewing of lymph flow through the superficial vessels and can be helpful in ensuring the patency of LVA. We also use it preoperatively to map the lymphatic vessels and intraoperatively in our modified liposuction procedure for advanced stages of lymphedema (fibro-lipo-lymph-aspiration with lymph vessel sparing procedure), in order to subsequently avoid these channels with the liposuction cannula to prevent further damage to vulnerable lymphatic vessels.
However, it is very important to note that ICGL is limited to viewing the superficial lymphatic vessels. In this sense, it should not be used for diagnostic purposes in the initial evaluation of a person with swelling, as excluding superficial lymphatic vessel problems does not exclude the diagnosis of lymphedema, which may be based only on deep lymphatic vessel obstruction or damage. Instead, we recommend that the most appropriate tool be chosen for the particular purpose for which it is needed: lymphoscintigraphy for diagnosis, preoperative planning, and preventive approaches and ICGL for preoperative and intraoperative real-time viewing of superficial lymph flow.
General Considerations of the Surgical Treatment of Lymphedema
Derivative Approaches
LVA techniques involve joining an appropriate lymphatic vessel to a collateral branch of a main vein and ensuring that the vein has competent valvular function and continence. This is essential to prevent reflux of the blood into the lymphatic vessel and, thereby, thrombosis of the anastomosis. Anastomoses created in close proximity to a valve in the vein are able to overcome the difference in pressure between the venous and lymphatic systems. In this way, the valvular pumping creates a suction that pulls the lymph immediately through the anastomosis to prevent thrombosis. The Center of Lymphatic Surgery and Microsurgery in Genoa, Italy, has obtained excellent stable clinical outcomes for more than 40 years by utilizing MLVA/MLVLA techniques in a single surgical site. Anastomoses are performed at a single site using larger lymphatic vessels attached to collateral branches of the main veins close to vein valves in order to avoid backflow of blood and the closure of the anastomosis. As explained later, a single-site approach also minimizes the number of incisions and, thereby, the potential entry sites for infection.
Blue patent violet dye (BPV) (a sodium or calcium salt of diethylammonium hydroxide) is used intraoperatively to identify properly functioning lymphatic vessels at the surgical incision. Healthy-appearing lymphatics found at the site of surgical operation are directly introduced together into the vein by a U-shaped stitch and then fixed to the vein cut-end by means of additional stitches between the vein border and the perilymphatic adipose tissue. The MLVA we create by using lymphatic vessels with the perilymphatic tissue intact ensures that these vessels are well functioning, and this also helps to prevent thrombosis. At the end, the first U-shaped stitch is removed to avoid the risk of closure of lymphatic collectors. With the use of the BPV, properly functioning lymphatics appear blue, and the passage of blue lymph into the vein branch verifies the patency of the LVA under the operating microscope when the anastomosis is completed ( Fig. 21.1 ).
For lower limb lymphedema, the MLVAs are created at the site of a single incision made at the subinguinal region. For upper limb lymphedema, MLVAs are created in the upper middle-third of the volar surface of the arm, using both surface and deep afferent lymphatic collectors that are visualized by the BPV. Deep lymphatics are generally located between the humeral artery, vein, and medial nerve and introduced, with a telescopic technique, into a patent branch of one of the humeral veins containing a well-functioning valve.
Multiple Lymphatic-Venous-Lymphatic Anastomoses
It is possible to perform MLVAs at the same time. The most important requirement is that the vein branches are patent. Duplex scanning is performed in all patients to identify any venous disorders that might be contributing to the edema. In most patients, it is possible to correct these venous dysfunctions at the same time as the microsurgery, such as performing valvular-plasty for venous insufficiency with 6-0 nylon sutures. In the minority of cases, venous disease is an indication for performing a venous graft between the lymphatic collectors above and below the site of lymphatic obstruction, as the valvular incompetency of the diseased veins would compromise the efficacy of the anastomoses if MLVA were performed instead. This venous-bridge type of graft is called a lymphatic-venous-lymphatic anastomosis. Competent venous segments are harvested from the same operative site or can be taken from the forearm (usually the cephalic vein). The length of the grafted vein section varies from 7 to 15 cm as needed. It is essential to collect several lymphatic collectors to join to the distal end of the vein to ensure that the vein segment is filled with sufficient lymph to avoid closure due to subsequent fibrosis development. The competent valves of the vein segment are vital for directing the flow of lymph in the correct direction and avoiding gravitational backflow or reflux. As with the LVA, the lymphatic collectors are directly introduced into the vein cut-ends by means of a U-shaped stitch, which is then stabilized with additional peripheral stitches.
Clinical Experience
Between 1973 and May 2019, 5136 patients received microsurgical treatment for peripheral lymphedema in Genoa, Italy: both upper and lower limb lymphedema and primary and secondary etiology. Patients were followed for a minimum of 5 years to a maximum of 25 years postoperatively. The follow-up consisted of periodic clinical evaluations at 1, 3, 6, and 12 months after microsurgery, and then annually for a minimum of 5 years to more than 20 years. This close patient follow-up gives optimal control for the long-term clinical outcome.
Histological samples taken during surgery showed that primary lymphedemas typically involved lymph node dysplasias (LAD II according to Papendieck’s classifications ) with hypoplastic lymph nodes associated with sinus histiocytosis and a thick fibrous capsule and micro-lymphangio-adenomyomatosis. These dysplasias caused an obstruction to lymphatic flow that was evident in the changes in the afferent lymphatic collectors: these are dilated, swollen, and tortuous with thickened walls and reduced numbers of smooth muscle cells, which are further fragmented by numerous fibrotic elements.
In our clinical experience, secondary lymphedemas were usually related to lymphadenectomy and radiotherapy as part of oncological treatment (carcinoma of the breast, uterus, penis, bladder, prostate gland, and rectum and seminoma of the epididymis) or for complications of minor surgeries for varicose veins, groin and inguinal hernias, lipomas, tendinous cysts, or inguinal and axillary lymph nodal biopsies. Most of the lymphedemas treated were at stages IIA (39%) and IIB (52%), with 3.8% at stage IB and 5.2% at stages IIIA and B (according to the Campisi staging system for lymphedema—refer to Table 21.1 ).
Clinical outcomes improve the earlier that microsurgical techniques are applied in the treatment of peripheral lymphedema, due to the absence of, or minimal, fibrosclerotic tissue changes in the lymph vessels walls and surrounding tissues that occur as a result of lymph stasis. Compared to preoperative conditions, patients obtained significant reductions in excess limb volume of over 86%, with an average of 73%, as measured by limb water volumetry and circumference ( Figs. 21.2 and 21.3 ). These results were stable over an average of 13 years of follow-up. Over 87% of patients with stage I or IIA lymphedema gradually stopped using conservative therapies over the length of the follow-up period. In patients with more advanced lymphedema (stages IIB, IIIA, and IIIB), 45% could decrease the frequency of physical therapies in the long-term. In all patients, infective rates, particularly lymphangitis, cellulitis, and erysipelas, considerably reduced by over 95% compared to preoperative conditions.
