Surgery of the Hemolymphatic System

Surgery of the Lymphatic System

General Principles and Techniques

Tissue for histopathologic examination of lymph nodes may be obtained by removing the entire node (lymphadenectomy) or by excising a portion of it. Lymphangiomas are benign tumors of peripheral lymphatics, and lymphangiosarcomas are malignant tumors of peripheral lymphatics.

Preoperative Management

Lymphadenomegaly is one of the more common lymphatic abnormalities of dogs and cats and may be caused by infection, inflammation, neoplasia (metastatic or primary), or systemic disease. It is important to distinguish generalized lymphadenomegaly from localized (regional) disease. With localized lymphadenopathy, areas drained by the node should be examined for evidence of infection, inflammation, or neoplasia. Conversely, one must remember that lymph node size does not necessarily correlate with disease, and neoplastic cells may be retrieved from normal-sized lymph nodes. Although cytology of lymph node and splenic aspirates is very specific for neoplastic and fungal diseases (i.e., you can trust the diagnosis if you find such cells), it is not sensitive (i.e., not finding cancer or organisms never eliminates such disease because fine-needle aspirates of lymph nodes and spleens can easily miss the cells or organisms). Nonetheless, fine-needle aspirates and/or fine-needle core biopsies should be done before lymph node and sometimes splenic biopsy, because finding neoplasia or fungal elements by these less invasive techniques will make more invasive techniques unnecessary. The reader is referred to a medicinal text for an in-depth discussion of lymph node cytology.

NOTE • If several lymph nodes are enlarged, avoid biopsying the submandibular node because this node tends to be reactive.

The mandibular, superficial cervical (prescapular), superficial inguinal, and popliteal lymph nodes are palpable in most animals (Fig. 24-1). The tonsils may be visualized in the oral cavity, and facial lymph nodes may be found in some normal animals. In dogs, the maxillary, accessory axillary, cervical, femoral, and retropharyngeal lymph nodes usually are palpable only when enlarged; however, the axillary node may be located readily in cats, even when it is only moderately enlarged. Unless the animal is extremely thin or cachectic, sublumbar and mesenteric lymph nodes must be at least moderately enlarged to be detected on rectal or abdominal palpation. The texture of the enlarged node and sensitivity to pressure or manipulation should be noted. Acute enlargement (i.e., suppurative lymphadenitis) can be associated with pain, but lymphoid neoplasia usually causes painless enlargement. Metastatic neoplasia and fungal infections sometimes cause nodes to become fixed to surrounding tissue. Clinical signs may result from lymphadenomegaly (e.g., coughing caused by tracheal compression by enlarged hilar lymph nodes, constipation resulting from sublumbar lymphadenopathy).

FIG 24-1 Location of palpable lymph nodes.

Lymphangiomas are rare, benign neoplasms originating from lymphatic capillaries. They are believed to be developmental anomalies associated with failure of primitive lymphatic sacs to establish venous communication. These endothelial sprouts continue to grow, infiltrate surrounding tissue, cause pressure and subsequent necrosis, and form cystic structures. They typically manifest as large, fluctuant swellings that are noticed incidentally or because of interference with normal structures as a result of expansive growth. They have been identified arising from subcutaneous tissue, the nasopharynx, and the retroperitoneal space of dogs and in the liver and the mediastinum in cats. Affected dogs usually are middle-aged or older; however, lymphangiomas may occur in young dogs. In a recent study of vascular tumors in 420 dogs, only one lymphangioma was observed (Gamlem et al, 2008). Treatment for lymphangioma consists of complete surgical excision or marsupialization. A lymphangiomatous mass arising from the right palatine tonsil was removed without complications or evidence of recurrence in an 8-year-old female dog (Miller et al, 2008). Lymphangiosarcomas (Fig. 24-2) are malignant tumors that arise from lymphatic capillaries. They are locally aggressive, and metastasis to regional lymph nodes, lungs, spleen, kidneys, and bone marrow has been reported. Even without metastasis, the local invasiveness of this tumor often necessitates euthanasia. Surgical resection may be considered; however, cure is unlikely. These tumors have been reported most often in medium- to large-breed dogs. They may occur in young dogs; however, most affected dogs are middle-aged or older. Diagnosis may be made by histopathology, electron microscopy, immunohistochemistry, tissue culture, and/or endothelial expression of glycoconjugates (Williams, 2005). Histologically, lymphangiomas and lymphangiosarcomas are composed of vascular spaces lined by endothelial cells and focal lymphoid aggregates divided by connective tissue stroma. Unlike hemangiomas, the cystic spaces of these tumors are not filled with blood.

FIG 24-2 Massive head and neck swelling in a dog with diffuse lymphangiosarcoma.

Anesthesia

Superficial (e.g., popliteal) nodes can be excised using local anesthetic and sedation if necessary; however, short-duration general anesthesia usually facilitates extirpation.

Antibiotics

Perioperative antibiotics are seldom indicated in animals undergoing lymph node biopsy or removal.

Surgical Anatomy

Lymph nodes are bean-shaped structures with a convex surface and a small flat or concave hilus (Fig. 24-3). They usually are found encased in fat at flexor angles or joints, in the mediastinum and mesentery, and in the angle formed by the origin of larger blood vessels.

FIG 24-3 Structure of a lymph node, showing afferent and efferent drainage.

References

Gamlem, H, Nordstoga, K, Arnesen, K. Canine vascular neoplasia—a population-based clinicopathologic study of 439 tumours and tumour-like lesions in 420 dogs. APMIS Suppl. 2008;125:41.

Miller, AD, Alcaraz, A, McDonough, SP. Tonsillar lymphangiomatous polyp in a dog. J Comp Pathol. 2008;138:215.

Nyman, HT, O’Brien, RT. The sonographic evaluation of lymph nodes. Clin Tech Small Animal Pract. 2007;22:128.

Williams, JH. Lymphangiosarcoma of dogs: a review. J S Afr Vet Assoc. 2005;76:127.

Specific Diseases

Lymphedema

Definitions

Lymphedema is an accumulation of fluid in the interstitial space. Primary lymphedema is caused by an abnormality or disease of lymph vessels or lymph nodes; secondary lymphedema occurs as a result of lymphatic obstruction of the nodes or vessels by neoplasia, filariasis, lymphoproliferative disorders, or some other infiltrative process or surgery.

General Considerations and Clinically Relevant Pathophysiology

Lymphedema results from a disturbance of the equilibrium between the amount of fluid in the interstitial space that needs to be cleared (capillary filtrate) and the capacity of the lymphatic and venous systems to remove this fluid. Possible causes include (1) overload of the lymphatic system, (2) inadequate collection by the lymphatic terminal buds, (3) abnormal lymphatic contractility, (4) insufficient lymphatics, (5) lymph node obstruction, and (6) central vessel (i.e., thoracic duct) defects. Regardless of the cause, edema results when capillary filtration exceeds the combined resorptive capabilities of the venous and lymphatic systems. This edema is relatively protein rich (2 to 5 g/dl). Because of the resultant high osmotic pressure, additional fluid is pulled into the interstitial space, worsening the edema. If the lymphatic system cannot adequately drain this interstitial fluid, collagen deposition and fibrosis may result. Hence, although the early stages are reversible, chronic edema is associated with thickening and fibrosis of tissue, making treatment difficult. The domestic species most commonly reported to have lymphedema is the dog.

Lymphedema may be a result of a primary defect in the lymphatic system or may occur secondary to other diseases or surgical procedures. Distinguishing between primary and secondary lymphedema often is difficult. Lymph node obstruction, although more commonly associated with secondary lymphedema, has been associated with primary lymphedema. Many of the dogs reported with primary lymphedema have had small or absent lymph nodes. Perhaps the initial defect in some dogs with lymphedema is fibrosis of the lymph nodes, which leads to secondary obstructive changes in the lymphatic vessels. As the vessels dilate, they lose contractility, and the lymphatic valves become permanently nonfunctional. Secondary lymphedema may be caused by conditions that increase the rate of interstitial fluid formation as a result of altered capillary permeability (e.g., trauma, heat, irradiation, infection). Venous congestion (i.e., because of heart failure) may also cause lymphedema by reducing fluid resorption. Secondary lymphedema can result from neoplasia or infiltration of lymph nodes by filaria, such as Wuchereria bancrofti and Brugia timori, and from lymphoproliferative disorders. Secondary malignant lymphedema was recently reported after mastectomy in two dogs (Kang et al, 2007). Both dogs had large edematous lesions associated with lameness in the right hindlimb following surgery. Obstruction of lymph flow in the lymphatics of the right hindlimbs was shown with lymphangiography in one dog and lymphoscintigraphy in the other dog.

NOTE • Lymphedema may be caused by primary lymphatic abnormalities or may occur secondary to other diseases or surgery. Distinguishing between primary and secondary lymphedema often is difficult. The age of onset of clinical signs does not help distinguish the two conditions in many cases because middle-aged animals may have acute signs of lymphedema that occur secondary to congenital lymphatic abnormalities.

Diagnosis

Clinical Presentation

Signalment

Primary lymphedema usually is noted at birth or shortly thereafter; however, older animals may develop lymphedema associated with congenital abnormalities. The lymphatic system may function normally until a precipitating cause (e.g., infection, trauma, surgery) overwhelms the marginal lymphatic system. Congenital, hereditary lymphedema has been reported in Bulldogs and Poodles. A gender predisposition is not evident.

NOTE • Congenital lymphatic abnormalities may not cause lymphedema until the animal is several years old. Clinical signs of primary lymphedema may be precipitated by infection, trauma, or surgery.

History

The age of onset, progression of disease, extent of involvement (unilateral or bilateral, pelvic limb or forelimb), and history of previous surgery, trauma, or exposure to infectious agents should be ascertained. Lymphedema typically manifests as a spontaneous, painless swelling of the extremities with pitting edema. The onset may be insidious. The rear limbs are more commonly affected, and the swelling may be unilateral. Lymphedema usually begins in the distal extremity and progresses proximally. In severely affected animals, all four limbs and the trunk may be edematous. Although the patient may be less active than normal because of the weight of the limb or may carry the limb when ambulating, lameness and pain are uncommon without massive enlargement or cellulitis.

Physical Examination Findings

The diagnosis of lymphedema usually is made on the basis of clinical signs (Fig. 24-5). The limb generally is not excessively warm or cool. Although the condition often is bilateral, the degree of swelling frequently is greater in one limb. Occasionally, swelling may be precipitated by minor trauma or superficial skin infection. Fibrosis occurs as the edema becomes chronic, and the edema tends to progressively pit less until pitting is absent. With chronic edema, massage and rest do not appreciably reduce the size of the limb.

FIG 24-5 A 2-year-old Boxer with lymphedema. Note the massive swelling of the right rear limb.

Laboratory Findings

No specific laboratory abnormalities are found with lymphedema. It is important to note that these animals are not hypoalbuminemic; hypoalbuminemia is always an important differential for edema, even localized edema.

Differential Diagnosis

The key differential diagnosis is abnormality of the venous system, such as venous stasis or arteriovenous fistula. The clinical signs usually are adequate to differentiate lymphedema from edema caused by venous obstruction. Typical changes with edema caused by venous obstruction include varices, stasis hyperpigmentation, and cutaneous ulceration. Arteriovenous fistulae are vascular abnormalities in which a direct communication exists between an adjacent artery and vein. They may be congenital or acquired (e.g., after trauma, neoplasia, infection, or iatrogenic ligation of an artery and vein together). Clinical signs with arteriovenous fistulae vary depending on the location; however, palpation of strong pulsatile vessels, often of a fremitus or thrill, and auscultation of a machinery murmur (i.e., bruit) are classic findings. Angiography is necessary to confirm the diagnosis and determine the size, extent, and location of the fistula. The physical examination should eliminate systemic causes of bilateral edema, including heart failure, renal failure, cirrhosis, and hypoproteinemia. Other differential diagnoses include trauma, neoplasia, and foreign bodies.

Medical Management

In the early stages of lymphedema, before the development of fibrosis, nonsurgical therapy may reduce the swelling and make the patient more comfortable. Nonsurgical therapy consists of heavy bandages or splints that exert pressure on the limb, meticulous care of the skin to prevent infection, weight control, and appropriate use of antibiotics to treat and prevent cellulitis and lymphangitis. Drugs that have been used to treat human patients with lymphedema include steroids, diuretics, anticoagulants, and fibrinolysin inhibitors. For the most part, the proposed benefits of these pharmaceuticals have not been substantiated. Long-term treatment of lymphedema with diuretics is contraindicated. Diuretics act by removing fluid from the tissue; proteins that are not reabsorbed become increasingly concentrated, further damaging tissues.

NOTE • Medical therapy often is ineffective in substantially reducing swelling caused by lymphedema; however, medical management has received little attention in veterinary medicine. Amputation is a reasonable alternative for unilateral lymphedema, particularly when it interferes with limb function and when initial medical management is ineffective.

The benzopyrones are a group of drugs that have been used to successfully treat experimental lymphedema in dogs and spontaneous lymphedema in human beings. All the drugs in this group appear to reduce high-protein edema. Their main action appears to be stimulation of macrophages, which promotes proteolysis. Protein fragments can then be reabsorbed into the blood. These drugs are active orally and topically, are inexpensive, and are relatively free of side effects. Included in this category of drugs are coumarin (5,6 benzo-[a]-pyrone), O-(β-hydroxy-ethyl)-rutosides, diosmin, and rutin. Recommended dosages for human beings are 440 mg/day of coumarin and 3 g/day of rutosides, diosmin, and rutin (Box 24-1). Although these drugs (e.g., rutin) are being investigated for spontaneous lymphedema in dogs, their efficacy currently is uncertain.

Box 24-1 Benzopyrones for the Treatment of Lymphedema

Rutin *

50-100 mg/kg given PO q8hr

PO, Oral.

^*This is one drug in the family of benzopyrones; other drugs may be as or more effective. The dose is an extrapolation of that used in human beings; side effects appear rare, but controlled studies have not been performed.

Lymphography and Lymphoscintigraphy

The classic diagnostic tool has been direct lymphography (lymphangiography) (see p. 691 for a description of the technique). Oil-based contrast media are contraindicated in patients with primary lymphedema because the high volume of contrast medium necessary to visualize the lymphatics and the propensity for extravasation may further damage existing lymphatics. Lymphoscintigraphy, an alternative method of imaging the peripheral lymphatics, involves intradermal injection of high molecular weight, radiolabeled colloids. A gamma camera is used to obtain images of the affected limb over time to observe the progression of radioactivity through the lymphatics. Primary lymphedema typically shows slow absorption of the radiopharmaceutical, reduced visualization of lymphatic vessels and lymph nodes, and no interstitial activity. Secondary lymphedema typically shows poorly visualized primary lymph vessels and dilated secondary lymph vessels. Significant interstitial activity is also noted.

Surgical Treatment

Except for amputation, no current surgical treatment offers a cure for lymphedema. Numerous therapies have been described in human patients, including lymphangioplasty, bridging procedures, lymphaticovenous shunts, omental transposition, superficial to deep anastomosis, and excision (with or without skin grafting). These techniques have not been adequately evaluated in dogs with spontaneous lymphedema. Lymphangiography rarely provides information that helps in management of animals with spontaneous lymphedema, but it occasionally defines the underlying lymphatic abnormality (i.e., hypoplasia, aplasia, or hyperplasia of lymphatics). It is a tool that must be correlated with other historical and physical findings. Biopsy samples of affected tissues should be submitted because lymphangiosarcoma, a highly malignant neoplasm, has been reported to occur in human beings with long-standing lymphedema. The technique for lymphangiography is described on p. 691.

NOTE • Biopsies should be performed in lymphedematous animals to rule out neoplasia. Neoplastic transformation of chronically edematous tissue may occur.

Preoperative Management

Perioperative antibiotics are indicated in patients undergoing lymphangiography because the risk of subsequent lymphangitis is high. Before performing other preoperative procedures, inject 1 ml of 3% Evans blue dye between the second and third, or third and fourth, digits to aid in the visualization and cannulation of lymphatics.

Anesthesia

General anesthesia is required for direct lymphangiography.

Surgical Anatomy

The lymphatic system of the extremities can be divided into two parts: superficial and deep (i.e., muscular) lymphatics. The superficial system appears to be the one most commonly involved in lymphedema. This is the system of lymphatics observed during pedal lymphangiography (Fig. 24-6). These lymphatics empty into a valved group of vessels found at the junction of the dermis and subcutaneous tissue. Lymph then drains into afferent lymphatics in the subcutaneous fat. The superficial lymphatics of the pelvic limb consist of a larger medial group and a smaller lateral group. Lymphatics follow the branches of the medial saphenous vein and drain into the superficial inguinal lymph nodes. Efferent lymphatics from the lymph nodes drain into the larger lymphatic ducts. The deeper lymphatics drain the fascial planes surrounding skeletal muscles (lymphatics are not found in skeletal muscle bundles), joints, and synovium. Deep lymphatic collector vessels accompany the main blood vessels of the extremities. Controversy continues as to whether the two lymphatic systems (superficial and deep) communicate; however, communications usually appear to be a result of a lymphatic pathologic condition or a response to abnormal lymph flow. The lumbar lymph trunks receive vessels from the pelvic limbs, the abdominal lymph nodes, and the intestines before uniting to form the cisterna chyli.

FIG 24-6 Pedal lymphangiogram in a dog. The superficial lymphatic system is filled with contrast.

Positioning

Position the animal on the radiology table in lateral recumbency with the affected limb down and the opposite limb retracted from the radiographic field. Prepare and drape the dorsomedial aspect of the metatarsus for aseptic surgery.

Surgical Technique

Direct Lymphangiography

Make a 5-cm skin incision over the mid-dorsomedial metatarsal region. Use sharp and blunt dissection until a blue-stained, superficial metatarsal lymphatic vessel is identified (Fig. 24-7). Meticulously dissect the lymphatic free from surrounding tissue with fine, blunt dissection probes, and cannulate the lymphatic using a lymph duct cannulator or a 27 or 30 gauge over-the-needle catheter. Inject a small amount of sterile saline into the catheter or cannulator to verify patency. Then manually infuse an aqueous-based radiographic contrast agent into the lymphatic vessel. Take radiographs immediately after the injection (Fig. 24-8); additional radiographs may be taken, depending on the rate of lymphatic transport of the contrast agent, which varies from patient to patient. Upon completion of the lymphangiogram, withdraw the cannulator, ligate the lymphatic vessel, and close the incision in a routine fashion.