Whereas the mainstay of treatment of lymphedema and other lymphatic disorders has long been non-operative, there is, nonetheless, a century of history of attempts to simplify management and improve patient outcomes using a variety of surgical approaches. These have included efforts to remove unsightly tissue overgrowth and lymphatic tumor masses; promote lymph drainage through prelymphatic tissue channels, skin flaps, and omental transplants; and reroute obstructed lymph flow through direct lymphatic and lymph node shunts back into the venous system. Recent advances in microsurgery, refinements in noninvasive dynamic lymphatic system imaging, and improved approaches to resection have built upon this historic tradition and the contributions of pioneering surgical lymphologists to make lymphatic microsurgery and surgery of lymphatic disorders an increasingly important, safe, and practical option in these chronic vexing disfiguring, disabling, and at times, life-threatening congenital and acquired conditions. Moreover, future improvements in the scope and outcome of these procedures include minimally invasive and robotic approaches possibly coupled along with tissue engineering and stem cell and tissue transplantation. These improvements, and ultimately fetal restitution or reconstruction, to prevent or treat these lymphatic disorders will require both the intellect and skill of surgeons on research teams and in clinical multimodal management.

Operations for the treatment of patients with lymphatic disorders can be traced back to 1908 when Handley¹ described his technique of “lymphangioplasty,” consisting of running silk threads subcutaneously in an effort to provide a conduit for lymphatic drainage. The procedure was eventually abandoned because postoperative infection and spontaneous extrusion of the implanted foreign material commonly occurred. Shortly after this, in 1912, Kondoleon² introduced the predominant surgical procedure for lymphedema that would be used for 50 years thereafter. He based the procedure named after him on observations in dogs that lymph flow passed through the muscular system and drained through the subcutaneous tissue and that furthermore, in human elephantiasis, that fascia was unusually hard, thickened, and fixed to the surrounding adipose tissue.³ The Kondoleon procedure, which consists of a wide excision of the fascia with a concomitant partial excision of the hypertrophic adipose tissue, was hailed as a unique advance in surgical treatment for patients with elephantiasis at the 1918 American Medical Association meeting⁴ and was widely used by leading surgeons around the world up until the 1960s. Other excisional operations, such as Charles’ total resection of subcutaneous tissue,⁵ Thompson’s subfascial drainage of a scarified skin flap,⁶ and Servelle’s total surface lymphangiectomy,⁷ also aimed at removing excess tissue to decrease volume of the swollen extremity.^{8,9,10,11,12,13,14,15,16} However, prolonged hospitalization, poor wound healing, long surgical scars, sensory nerve loss, residual edema of the foot and ankle, and poor cosmetic results have been important problems resulting from these major debulking operations. Their use today is largely restricted to only the most advanced cases of elephantiasis that do not respond to conservative measures; localized nodules of lipolymphedema in massive obesity¹⁷; and swelling deformities in body regions less accessible to effective compression, such as the genitalia (Figure 42-1). Because adipose hypertrophy is commonly seen in chronic advanced lymphedema, Brorson et al^18,19 recently refined liposuction techniques to debulk upper limb adipose volume in breast cancer patients and in selected cases of lower limb lymphedema.

The first use of microsurgery was described in 1962 when Cockett and Goodwin²⁰ performed an anastomosis of a dilated lumbar lymphatic to the spermatic vein to treat a patient with chyluria. From this first procedure, subsequent developments in microsurgical techniques (as described below) have enabled lymphatic–venous anastomosis to emerge as a feasible treatment option for patients with lymphedema.

In 1977, O’Brien and coworkers^21,22 described their use of microlymphatic surgery for the treatment of patients with secondary obstructive lymphedema. They used three or more lymphaticovenous anastomoses at or above the elbow (or knee) and observed a reduced incidence of cellulitis postoperatively. The microlymphatic techniques were applicable to both the upper and lower limbs, and they also applied them to localized cases of obstructive lymphedema after trauma and congenital constriction bands. They emphasized that considerable experience in microvascular surgery was required for performing the procedure. Their results in obstructive secondary lymphedema were encouraging, even though the authors remarked that a long-term evaluation of the clinical outcome was required before judging the potential of these techniques.

The field was advanced in 1981 when Degni^23,24 introduced an original technique of lymphatic–venous anastomosis for use in lymphedema of the limbs. The procedure was easily performed and was applicable to both the upper and lower limbs and for the thoracic duct or any blocked lymphatic vessels of the abdomen. He used this technique to treat lymphedema caused by surgical resection of benign tumors (lipomas of the thigh), reconstructive procedures (pendulous abdomen, plastic surgery of the thigh), orthopedic operations on the knee, and after varicose vein stripping. The purpose was to divert the lymph into a vein in cases of blocked lymphatic vessels, particularly when lymphographic findings demonstrated good function and intact permeability of lymphatic vessels. A longitudinally divided needle was used to introduce the lymphatic trunk into the vein, pulling the lymphatic into the venous lumen and fixing the lymphatic to the upper venous wall with one suture.

At almost the same time (1982), Clodius^25,26 reported that microsurgery for primary and secondary lymphedema, consisting of shunts between lymphatic vessels and veins, was a well-established surgical technique. Problems arose from irreversible changes in the peripheral lymphatic system and in the connective tissues as well as the obliteration of the deep lymphatics best suited for lymphaticovenous anastomoses in more chronic lymphedema. He therefore cautioned that lymphaticovenous shunts should be performed early before fibrotic tissue changes appear.

As the techniques were becoming more widespread, two groups reported larger data sets. In 1985, Huang and coworkers²⁷ described their experience of 110 cases of lymphedema treated by microlymphaticovenous anastomosis with very satisfactory immediate and long-term results in 79.1%. Their data suggested that the quality of results was proportional to the number of anastomoses. Krylov and coworkers²⁸ reported an experience of 510 patients with primary (~two-thirds of cases) or secondary lymphedema in the upper and lower extremities. Notably, the most favorable results were obtained in secondary obstructive lymphedema cases associated with lymphatic hypertension, which contributed to better functioning of the lymphaticovenous anastomoses. In 1987, Zhu and coworkers²⁹ reported a clinical experience of 185 limbs with lymphedema treated by lymphaticovenous anastomosis with excellent results achieved in 73% of cases.

In 1988, Al Assal and coworkers³⁰ reported on experimental studies in dogs using a new technique of microlympho–venous anastomosis to improve long-term patency rates and clinical results in lymphedema therapy. Technical points, such as an oval window on the wall of the vein and a few sutures piercing only two lymphatic layers, adventitia and media, outside the lumen, were emphasized for successful results. Three methods for assessment of patency of anastomoses were used: observation with the operating microscope of dye transit across the anastomotic site, lymphography, and histopathologic examination. Based on encouraging results, the authors suggested that end-to-side anastomosis might be the technique of choice.

In 1988, Olszewski^31,32,33,34 published his personal 20-year clinical experience in diagnosis and treatment of patients with various types of lymphedema of the lower limbs with microsurgical lymph node–vein and lymph vessel–vein anastomoses. He limited indications for surgical therapy of lymphedema to a carefully selected group of patients with local, segmental obstruction of proximal lymphatics with demonstrably patent peripheral lymphatics and at least partial preservation of contractility. He reported that in his practice, long-term penicillin therapy was indispensable before surgery in patients with a history of lymphangitis.

A critical review of microsurgical lymphovenous anastomosis (LVA) for the treatment of patients with lymphedema was published by Gloviczki and coworkers³⁵ in 1988. Their group performed LVAs to treat patients with chronic lymphedema and reported a mean follow-up at 36.6 months. They concluded that LVA offered a promising physiologic treatment, particularly in the secondary lymphedemas, and that lymphoscintigraphy was found to be a suitable method for both identifying patent lymphatic channels before surgery and determining the function of LVA after operation.

Ho and coworkers,³⁶ also in 1988, reported their results in a series of patients with secondary obstructive lymphedema treated by microlymphatic bypass. The procedures in the lower and upper limbs were described. Preoperative assessment with lymphangiography and lymphoscintigraphy was used to assess suitability for the procedure. Postoperatively, patent lymph collectors were demonstrated by lymphoscintigraphy. The authors also emphasized that microlymphatic bypass should be carried out before the peripheral lymph collectors were destroyed or permanently damaged by increasing backpressure and recurrent infection.

In a different approach, in 1990, Baumeister and Siuda³⁷ described their initial experience with microsurgical lymphatic grafting in the treatment of patients with lymphedemas. Lymphatic grafts were anastomosed to peripheral lymphatics distal to and central lymphatics proximal to the regional blockade. In the case of unilateral blockade at the groin or pelvis, the grafts connected the lymphatics of the thigh of the affected leg with lymphatics in the contralateral healthy groin. They have continued to perform this procedure albeit in a relatively small number of selected cases using lymphoscintigraphy to document graft patency.

In 1990, O’Brien and coworkers^38,39 reported their cumulative clinical experience in the treatment of patients with obstructive lymphedema by microlymphaticovenous anastomoses. They described subjective improvement in 73% of patients and, objectively, volume changes showed a significant improvement in 42% of cases, with an average reduction of 44% of the excess volume. The authors also emphasized the significant reduction in the incidence of cellulitis episodes after surgery. Their long-term results (average follow-up, 4 years) indicated that microlymphaticovenous anastomoses had a valuable place in the treatment of patients with obstructive lymphedema and perhaps should be the treatment of choice in selected patients. They also pointed out (as Clodius and Ho above) that improved results could be expected with earlier operations because patients referred earlier usually have less lymphatic disruption.

Despite advances in microsurgery, the most suitable operation for primary lymphedema remained unclear. A variety of tissue transplants and artificial substances had been used to facilitate drainage of peripheral lymph.^40,41,42 The greater omentum was used experimentally in the treatment of canine obstructive lymphedema by O’Brien and coworkers³⁸ in 1990 and Abalmasov and coworkers⁴³ in 1994. The findings indicated that experimental obstructive lymphedema in the dog could be reduced significantly by insertion of a vascularized omental graft. However, because there is no natural lymph nodal–venous (L-V) shunt within the greater omentum, the addition of an L-V shunt to omental transplantation in dogs seemed to increase the effectiveness of the autotransplanted omentum for draining hindlimb lymph. Continued use of omental transplants has continued in select situations.

Derivative Approaches

The first microsurgical derivative operations were those using L-V shunts. These have been largely abandoned (except in endemic areas of lymphatic filariasis such as India where thousands of these procedures have been performed and lymphatic channels, even in lymph nodes, are often widely dilated) because of the high rate of anastomotic closures caused by the thrombogenic effect of lymph nodal pulp on the venous blood and the frequent re-endothelization of the lymph nodal surface. One of the possible modifications of this technique is the use of lymph nodal capsular patch with its afferent lymphatics (lymph nodal capsular–venous anastomosis). This method has been carried out predominantly in children because it is technically feasible even in cases of very small lymphatic and venous structures.

Because of the difficulties encountered with L-V shunts by surgeons worldwide, the next approach was to use lymphatic vessels and directly anastomose them to veins. The first of these operations at the University of Genoa were performed using an end-to-side (lymph to blood) technique.⁴⁴ Lymphatic collectors were introduced inside the vein, and the inferior edge of the lymphatics introduced into the vein lumen acted as valves to avoid backflow of blood into the lymphatics and thereby preventing occurrence of thrombosis. More recently, the preferred techniques has been telescopic multiple lymphatic–venous anastomoses (Figures 42-2, 42-3, 42-4). 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. At the end, the first U-shaped stitch is removed to avoid the risk of closure of lymphatic collectors. With the use of patent blue dye (a sodium or calcium salt of diethylammonium hydroxide), properly functioning lymphatics appear blue, and the passage of blue lymph into the vein branch verifies the patency of the lymphatic–venous anastomosis under the operating microscope when the anastomosis is completed (see Figures 42-2 and 42-4).

For patients with lower limb lymphedema, anastomoses are performed at the subinguinal region. Lymphatic–lymph nodal superficial structures are isolated, and all afferent lymphatics are used for the operation. Lymph nodes are subjected to histopathologic examination. The usual finding in primary lower limb lymphedemas is a varying grade of nodal fibrosclerosis and thickening of the nodal capsule but with normal afferent lymphatic vessels.

Alternative technical microsurgical solutions are available depending on the anatomical conditions at the site of operation. It is possible to perform multiple lymphatic–venous anastomoses at the same time, and the important feature is that the vein branch is patent. It is necessary to test the patency of venous valves because it is mandatory to carry out an external valvuloplasty to correct the valvular insufficiency before performing anastomoses in cases of incompetent venous valves.^45,46

For upper limb lymphedema, lymphatic–venous anastomoses are performed at the medium third of the volar surface of the arm using both superficial and deep lymphatic collectors, evidenced by the blue dye. Deep lymphatics are found in between the humeral artery and vein and the median nerve. The vein used for anastomoses is a patent branch of one of the humeral veins, and the technique most performed often is the telescopic one.

More than 1500 patients affected by peripheral primary and secondary lymphedema have been treated over the past 30 years at the University of Genoa mostly using lymphatic–venous derivative techniques. Primary lymphedemas largely included lymph nodal dysplasias (LAD II), according to Papendieck’s classification,^47,48 consisting of hyperplastic lymph nodes with sinus histiocytosis and a thick and fibrous capsule with microlymphangioadenomyomatosis. In these cases, lymph flow obstruction was apparent as seen by alterations of the afferent lymphatics, which appear dilated and swollen with thickened walls and where smooth muscle cells are reduced in number and appear fragmented by associated fibrous elements.⁴⁹ In our experience, secondary lymphedemas^50,51,52 are largely caused by lymphadenectomy and radiotherapy performed for oncologic reasons (i.e., carcinoma of the breast, uterus, penis, bladder, prostatic gland, rectum, and seminoma of the epididymis), as well as for complications of minor operations for varicose veins, crural and inguinal hernias, lipomas, tendinous cysts, or axillary and inguinal lymph node biopsies. Most of the lymphedemas treated by microsurgery were at stages II (39%) and III (52%), and 3% of the patients were at stage Ib and 6% were at stages IV and V (Table 42-1).

Lymphoscintigraphy, performed with either technetium-99m(^99mTc)–labeled antimony sulfur colloid or ^99mTc-nanocolloid human serum albumin (90% of the particles >80 nm in size), was used in the diagnostic workup of patients with lymphedema and as a test for selecting patients for derivative microsurgical operations. Lymphoscintigraphy clearly discriminated whether edema was of lymphatic origin and provided important data about the etiologic and pathophysiologic aspects of the lymphedema.^{53,54,55,56,57,58,59,60,61,62}

Echo Doppler was performed in all patients to identify any venous disorders possibly associated with lymphedema. In most patients, venous dysfunctions were corrected at the same time of microlymphatico–venous anastomoses (i.e., valvuloplasty in case of venous insufficiency). In other cases, finding venous dysfunction contraindicated derivative lympho–venous shunts but at the same time facilitated referral of the patient for reconstructive microsurgical operations.

Conventional oil contrast lymphangiography was used only in selected patients with lymphedema caused by gravitational reflux to define more clearly the extension of the pathologic alterations and sites of lymphatic and chylous leakage.^63,64,65

Reconstructive Techniques

In cases involving the lower limbs, in which surgically uncorrectable venous disease exists, it is not advisable to use derivative lymphatic–venous techniques; therefore, reconstructive methods are used.^66,67,68 The most commonly used technique is the interposition of an autologous vein graft between lymphatics above and below the obstacle to lymph flow (see Figure 42-2D). The venous segment can be obtained from the same operative site or from the forearm (mostly the cephalic vein). The length of the graft is variable from 7 to 15 cm, and it is important to collect several lymphatics at the distal cut end of the vein so as to maintain the segment filled with lymph and avoid closure because of fibrosis. The valves of the veins are useful for the correct direction of the lymphatic flow and to avoid gravitational backflow. The technique of anastomosis is the telescopic one with introduction of lymphatics inside the vein cut ends by a U-shaped stitch, which is then fixed by some peripheral stitches.^69,70,71

Patients, Timing, and Results

The clinical outcome improves the earlier microsurgery performed owing to absent or minimal fibrosclerotic alterations of the lymphatic walls and surrounding tissues. Long-term results after more than 10 years have been excellent (>75% excess limb volume reduction compared with preoperative conditions) in 83% of patients, good (25%–50% decrease) in 14%, and poor (<25% edema reduction) in 3%.

Lymphoscintigraphy helps to verify the patency of microanastomoses long term after operation by direct and indirect findings (see Figures 42-3 and 42-4), including reduction of dermal backflow together with the appearance of preferential lymphatic pathways not visible before microsurgery, disappearance of the tracer at the site of lymphatic–venous anastomoses caused by direct tracer passage into the bloodstream, and earlier liver uptake compared with preoperative parameters (indirect patency test).

The optimal indications for lymphatic microsurgery are represented by early stages (1b, 2, early 3), lymphoscintigraphy showing a low inguinal or axillary lymph nodal uptake and minimal or absent passage of the tracer beyond this proximal nodal area, excellent patient compliance, and a lymphologic center where the patient can easily refer for any needs in addition to a center of lymphatic surgery where the patient undergoes this specialized surgery.

At later stages (advanced 3, 4, and 5), with absent visualization of lymphatic channels and regional lymph nodes, it is necessary to reduce the stage of the lymphedema by non-operative methods before microsurgery. After surgery, it is particularly important for these patients to be followed closely to improve the clinical outcome and maintain the short-term operative results for the long term (complete lymphedema functional therapy [CLyFT therapy]; Figure 42-5). In case of poor patient compliance, the results may be unsatisfactory. Relative contraindications to lymphatic microsurgery are represented by cases of lymphatic–lymph nodal aplasia (extremely rare), diffuse metastatic disease, and an advanced stage (V) not responsive to conservative therapy.

Lymphatic microsurgery represents a means to bypass the obstacle to lymph flow through lymphatic–venous drainage (lymphatic–venous anastomoses) or by using venous grafts between lymphatic collectors below and above the obstruction (lymphatic–venous–lymphatic plasty).^{72,73,74,75,76,77} Combined physical therapy^{78,79,80,81,82,83,84,85,86,87,88,89,90} nonetheless represents the initial treatment of patients affected by peripheral lymphedema, and it is best performed in specialized centers. The surgical timing occurs after completion of conservative treatment when further clinical improvement can no longer be achieved or recurrent lymphangitic attacks are not further reduced. Microsurgical operations can then be performed and provide further improvement in the condition.

Traditional debulking operations are presently used less often to treat patients with lymphedema except in cases of late stage lymphedema to reduce skin folds after marked edema reduction obtained by conservative physical and microsurgical methods, in body regions relatively inaccessible to effective compression such as the genitalia (see Figure 42-1), in advanced lymphatic filariasis at times combined with lymphatic–venous or nodal–venous anastomosis in the setting of widely dilated lymphatic channels (Figure 42-6),⁹¹ and in localized lipolymphedema associated with massive obesity and forced immobility.¹⁷