For decades, bipedal lymphangiography was the standard imaging test for nonsurgical assessment of the lymphatic system. At Stanford University (Stanford, CA), several thousands of lymphangiographies were performed over 20 to 25 years beginning in the 1960s.¹

The technique allows detection of enlarged lymph nodes in lymphadenopathy but may also demonstrate internal architectural derangements within normal-sized lymph nodes. It may further demonstrate the lymphatic origin of a known fluid collection as in cases with chylaskos, lymphocele, chylothorax, or lymphatic fistula. Using an iodinated glycerol ester (lipiodol) as a contrast agent, the technique has also been shown to induce granulomatous reactions at the site of lymphatic leakage and thereby may support its successful treatment.

Because lymphangiography is invasive and technically challenging and requires an experienced investigator as well as a compliant patient, its application has continuously decreased with the introduction of cross-sectional imaging.¹

Today sonography often serves as a first test for depiction of lymph nodes.² Image characteristics, such as a rounded shape, loss of the hyperechoic hilus reflex, node enlargement, and an enhanced cortical Doppler signal from increased vascularity, have been shown to indicate malignancy.^3,4 As a drawback, sonography is investigator dependent, may be time consuming, interferes with bowel gas, and often fails to precisely specify the origin of a fluid collection.

Indirect lymphangiography by intradermal pump injection of nonionic, water-soluble, dimeric, hexaiodinated contrast agents has been proposed but did not find its way into clinical routine.^5,6

Lymphangioscintigraphy is valuable in the assessment of lymphedema and the detection of the sentinel node as the first tumor-draining lymph node in patients with melanoma and breast cancer.^{7,8,9,10,11,12,13,14,15,16,17,18}

With cross-sectional imaging being optimized and broadly available, criteria for computed tomography (CT) and magnetic resonance (MR) detection of lymph nodes and lymphadenopathy has been described.^{19,20,21,22,23} These techniques offer three-dimensional capabilities, depict both lymphatic structures and the surrounding tissues and organs, and may even allow visualization of lymphatic structures not depictable by pedal lymphangiography (e.g., hypogastric and mesenteric nodes). On the other hand, these techniques often do not allow precise evaluation of the origin of a fluid collection and its leakage site and furthermore have no direct therapeutic potential.

Because CT and standard MR imaging (MRI) mainly apply size criteria for the assessment of lymph nodes, both techniques fail to detect lymphatic micrometastases within normal-sized lymph nodes. Therefore, the intravenous (IV) application of ultrasmall particles of iron oxide (USPIO) has been investigated for MR lymphography.²⁴ These particles are absorbed by the reticuloendothelial system (RES), which leads to a signal loss in normal nodes in T2-weighted sequences. Metastatic nodes, in which the RES is replaced by tumor cells, do not absorb USPIO and therefore do not show signal loss.²⁵ This technique may in the future allow better differentiation of benign and malignant lymphadenopathy. Fludeoxyglucose positron emission tomography (FDG-PET/CT), on the other hand, was shown to add important metabolic information to the anatomic CT depiction and thereby allows further characterization of lymph nodes²⁶ provided the nodes are sufficiently large to be detected by PET.

If both FDG-PET/CT and bipedal lymphangiography are to be performed in the same patient, lymphangiography should be performed after PET/CT to obviate false-positive findings in PET/CT.²⁷

The lymphatic system has two major functions. It is a major pathway for the drainage of interstitial fluid to the bloodstream, and it serves as a crucial component in the immune system.

Anatomy

The lymphatic circulation can be regarded as a one-way transport system, taking its origin at the capillary level. The lymphatic capillaries lie within the interstitial compartment of the connective tissue. The endothelial lining of these capillaries has gaps, so not only interstitial fluid, but also larger proteins, blood cells, and cellular debris can enter the lumen. The capillaries unify to lymphatic precollectors and lymphatic collectors consecutively. The afferent lymphatics anastomose with each other and drain to a regional lymph node. The lymph node is supplied by multiple afferent lymphatics, passing through its capsule into a subcapsular plexus. From this plexus, the lymphatic fluid passes through the sinuses of the cortex to the sinuses of the medulla and leaves the node through only one efferent lymphatic vessel. After passage of several lymph nodes, larger efferent lymphatic trunks carry the lymphatic fluid. These trunks have smooth muscle cells in their walls and valves, which allow centripetal flow only.²⁸ Although smaller, peripheral lymphatics run superficially underneath the skin, the more central trunks run deeply and adjacent to blood vessels in the abdomen and thorax. Paired lumbar trunks, draining both the legs and the pelvis, join at the level of the first or second lumbar vertebra to form a collecting space, known as the cisterna chyli. This space also receives the intestinal trunk from the region of the inferior and superior mesenteric arteries. The cisterna chyli is a saccular structure about 5 cm long. It gives rise to the largest lymphatic vessel, the thoracic duct, which runs along the spine and parallel to the descending aorta, passes the upper thoracic aperture, and finally drains into the left venous angle after receiving inflow from the left jugular and left subclavian trunk. On the opposite site, the right lymphatic duct drains the right arm and neck and leads to the right venous angle.²⁹

Physiology

Plasma fluid and proteins are filtered from circulating capillary blood into the interstitial space along with existing hydrostatic and osmotic pressure gradients.³⁰ This interstitial fluid is then mainly drained by postcapillary venules. Because of the osmotic pressure of the interstitium, a small portion of the fluid remains in the interstitial space and is reabsorbed by the lymphatic capillaries, which are freely permeable for proteins and cells. This lymphatic fluid generally resembles interstitial fluid in its protein composition. In the cisterna chyli and the intestinal trunks, especially in the postprandial period, the large amount of fat resorbed from the intestine and now emulsified in the lymphatic fluid gives the lymphatic fluid a milky and whitish appearance. The flow rate in the lymphatic system depends on the described formation of lymphatic fluid but also on its centripetal flow. The flow is mainly influenced by systemic venous pressure as well as the muscle pump mechanism in the lymphatic trunks and the correct functioning of their one-way valves. On the average, lymphatic drainage is about 2.5 L/d.

Lymph nodes have been shown to serve as a reservoir for white blood cells and have filter function within the lymphatic fluid stream. They assist protein resorption from the lymphatic fluid and play a crucial role in the immune system of the body. On the other hand, the lymph nodes are also a route for cancer spread and proliferation.³¹ The physiology and pathophysiology of the lymphatic function for the immune system and cancer spread clearly exceed the focus of this chapter and are not discussed here.

Because of the centripetal lymphatic flow described above, diagnostic lymphangiography through contrast injection at the foot level has been used for decades to demonstrate lymphatic anatomy from the lower leg to the venous angle. Cases with known or suspected lymphatic vessel leakage were especially investigated to reveal the site of lymphatic leakage and thereby facilitate preoperative procedure planning.

In recent years, some reports have documented the therapeutic potential of lymphangiography in cases with chyle leakage. This therapeutic potential of lymphangiography becomes evident when discussing a complication that occurred after the usage of lipiodol for dacryocystography.³² Perforation resulted in a granulomatous reaction at the leakage site and a consecutive phlegmone.

In another case, chylaskos was refractory to conservative treatment.³³ Because it ceased spontaneously after lymphangiography, different mechanisms were discussed for the noticed therapeutic effect. After local extravasation of lipiodol at the site of leakage, inflammatory and granulomatous reactions are induced, as discussed above. Second, lipiodol itself may mechanically obstruct the leaking vessel. Last, the lipiodol collection developing around the leakage site may mechanically compress the injured vessel, thereby preventing further extravasation.

Because lymphangiography requires skilled radiologists and is a time-consuming procedure for the staff and the patient, the focus of indication has shifted from diagnostic purposes to such cases lymphangiographed in a conservative therapeutic setup throughout the past decades. According to the experience of other authors and us, diagnostic lymphangiography is an almost abandoned procedure in modern radiology.¹

In summary, the current therapeutic lymphangiography indications are

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  Lymphocele

  
  
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  Lymphocutaneous fistula

  
  
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  Chlyaskos

  
  
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  Chylothorax

If necessary in children and pregnant women, the need for the procedure should be discussed interdisciplinarily and with the patient because of the use of radiation.

Further contraindications include known or suspected allergies to the contrast agent, local anesthetic, and the applied blue-dye. In patients with cardiovascular disease, particularly heart failure, angina, pulmonary insufficiency, emphysema, and pulmonary fibrosis, symptoms may be promoted through small pulmonary embolisms resulting from lipid droplets.³⁴ For this mechanism, patients with known right-to-left cardiac shunting must not undergo the procedure because of an increased risk of arterial emboli.^35,36,37

In the absence of contraindications, lymphangiography can be performed using the following instruments and technique.

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  Cutaneous disinfection solution (e.g., Braunoderm, B. Braun AG, Melsungen, Germany)

  
  
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  Lymphangiography needle or catheter (e.g., Lymphangiography Set, COOK Inc., Bloomington, IN)

  
  
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  Lidocaine 1% (B. Braun AG, Melsungen, Germany)

  
  
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  Methylene blue dye Vitis (1% Methylthioniumchlorid, Metyhlenblau Vitis, Neopharma GmbH, Germany)

  
  
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  Lipiodol (Guerbet, Roissy CDG Cedex, France)

  
  
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  Adhesive strips (Steri-Strips, 3M Health Care, Neuss, Germany)

  
  
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  Infusion pump (e.g., Perfusor, B. Braun AG, Melsungen, Germany)

Written informed consent must be obtained before the procedure.

In cases with known superficial lymphoceles, these may be punctured and drained before lymphangiography to diminish the pressure within the collection and facilitate the extravasation of contrast media at the leakage site (Figure 14-1). Basic equipment for local anesthesia and blue-dye application is positioned table-side (Figure 14-2).

The patient is positioned on the table in a relaxed supine position with bare feet. The skin of the foot is washed with local cutaneous disinfection (Braunoderm). After sterile draping, a mixture of 2 mL of lidocaine 1% and 2 mL of methylene blue dye (1% Methylthioniumchloride) is injected intra- and subcutaneously into the first and second interdigital space (Figure 14-3).

In patients with known lymphatic extravasation at the lower limb, monopedal lymphangiography of the affected leg is performed. In patients with known lymphatic leakage at the pelvic level, or central thereof, bipedal lymphangiography is mandatory.

Within a 10-minute break, the patient is encouraged to exercise his or her foot (e.g., by walking) to support lymphatic resorption of the injected dye. Then the course of the lymphatic vessels can be identified through the skin. Equipment for catheterization is placed table-side under sterile precautions (Figure 14-4).

After local anesthesia, a 2-cm longitudinal skin incision lateral to the base of the first metatarsal is made parallel to one of the visible lymphatic vessels, and a lymphatic vessel is exposed (Figure 14-5). If necessary, a vessel more proximal and closer to the ankle may be chosen. Surrounding soft tissues are restrained, thereby optimizing vessel access. The exposed lymphatic vessel is cannulated using a catheter or needle (e.g., Lymphangiography Set or De Roo needles Nos. 35 and 40 with spring and mandarin) (Figure 14-6). Intraluminal position is confirmed with careful injection of 0.5 cc of saline.