Fig. 54.5  Lymphangio­ scintigram performed after microsurgery shows the patency of the lymphaticvenous anastomoses more than 10 years after the operation. Site of LVA (arrow)

Question 5

Which of the following statements are true?

A.  It is not possible to prevent secondary lymphoedema.

B.  Arm Reverse Mapping (ARM) is able to identify arm lymphatics.

C.  TheLymphaticMicrosurgicalPreventiveHealingApproach(LYMPHA)offersthepossibility of a primary surgical approach in the prevention of secondary lymphoedema.

54.1  Commentary

Lymphoedema is a significant worldwide problem. It can be divided into primary and secondary. Primary lymphoedemas do not have any recognizable cause (idiopathic), although triggering etiological factors can often be found. Lymphoedemas that present at birth (congenital) are included in this category. These can be hereditary-familial (NonneMilroy’s disease), and are often associated with chromosomal abnormalities. Other primary lymphoedemas, may have an early or late onset, which can be triggered by minor trauma, infection or surgery. In females, the predisposing factors are often thought to be alterations in neurohormonal status (neuroendocrine lymphoedema).

Primarylymphoedemascanalsobeduelymphaticorlymphnodedysplasia,hypoplasiaor even hyperplasia, with increased lymph production, either together or in combinations. In most cases of hypoplasia, lymph node involvement is demonstrated and leads to the

progressivesecondaryalterationoflymphaticvessels.Thispatternissimilartothatseenwith secondary lymphoedemas resulting from lymphoadenectomy with or without radiotherapy.1 Approximately90%ofallprimarylymphoedemasarecharacterizedbyhypodysplasticalterations involving lymph nodes and lymphatics. This is characterized by a diminished ability to formanadequatecollateralcirculationinresponsetotrauma,infectionorsurgery.Inafurther 8–10%ofprimarylymphoedemas,anincreaseinthenumberandsizeoflymphaticcollectors can be demonstrated and are associated with lymphatic and lymph nodal dysplasia.2

Disorders in lymphogenesis often contribute to altered lymphodynamics. Increased lymph formation may result from pre-existing arterio-venous malformations, arteriovenous fistulae or angiodysplasias. In contrast, reduced or absent production of lymph can result from, agenesis, hypoplasia, or impaired permeability of lymphatics, and is very rare. Lymphodynamic disorders also include gravitational and chylous reflux pathologies. Lymph backflow (reflux) can be caused by insufficient anti-gravitational structures, normally represented by valves, the reticular myoelastic layer of the lymphatic walls, and the lymph node architecture.

Theetiologyofsecondarylymphoedemacangenerallybeidentifiedinthepatient’shistory orphysicalexamination.Thiscanbesecondarytotrauma,infection,inflammation,infestation (filarial), radiotherapy, surgery, paralysis or neoplasia. Secondary lymphoedemas often have somecongenitalpredisposition.Armlymphoedemasecondarytobreastcarcinomatreatment, forexample,occursin5–35%ofpatients,dependingonwhetheraxillarysurgeryisassociated with radiotheraphy.3 This is more likely to occur when there is no deltoid pathway.4 The deltoid route allows the drainage of lymph from the arm directly into the supraclavicular lymph nodes. The axillary nodes are therefore bypassed because of the congenital presence of an alternative route. With preoperative lymphoscintigraphic studies, both ipsilateral and contralateral arms can be compared to enable patients with a higher risk of developing secondary lymphoedema to be identified. Based on these observations, Tosatti’s classification of lymphoedemas (Fig. 54.6), proposed more than 30 years ago,5 remains valid. [Q1:A]

The differentiation between lymphoedema and phleboedema is by a history and clinical examination, paying attention to the time and conditions of onset, location, evolution, extent and volume of the edema. Lymphoedema is hard to the touch, while venous edema issoftandpitsunderfingercompression.Thisdifferencereflectstheunderlyingpathophysiology: stagnant lymph in the subcutaneous connective tissue is an excellent culture medium for fibroblasts. These mature into fibrocytes and form dense fibrosclerotic tissue.

Lymphoedematypicallybeginsproximally,whereasvenousedemaaffectsthedistalpart of the lower limbs with the notable exception of phlegmasia dolens, caused by acute deep thrombophlebitis of the iliofemoral veins. Unlike phleboedema, lymphoedema does not usually evolve into dystrophic and dyschromic skin lesions or ulcers. It is more likely, how- ever,tobecomplicatedbyacutereticularerysipeloidlymphangitis,causedbyGram-positive cocci infections. Mixed types of lympho-phleboedema may also exist, with predominance of either the venous or lymphatic component. These include stage III postphlebitic syndrome and angiodysplasias with arteriovenous shunting, as seen in Mayall’s syndrome.6

Currently, lymphangioscintigraphy and conventional oil contrast lymphography are the most suitable investigations of lymphatic and chylous edemas. Lymphangioscintigraphy is the most popular method used in screening lymphoedemas7, 8 as it is a non-invasive way of imaging both superficial and deep lymphatic circulations. Since it is non-invasive, it can easily be repeated in patients, especially after microsurgery. A small tracer dose of 99mtechnetium adsorbed in colloid spherules (colloid sulfide, rhenium, dextran) is injected. The

(primitive and secondary)

Mixed: associated to venous and much rarely arterial diseases

Fig. 54.6  Classification of chronic lymphoedema of the limb according to Tosatti

lymphotropicnatureofthesesubstancespermitsvisualizationofthepreferentiallymphatic pathways with a gamma-camera. This allows measurements of the flow rate and lymph node uptake. Tracer clearance evaluations are a useful measure of lymphodynamics especially in early lymphoedema.9 Direct lymphangiography10 is preferred, however, in the study of gravitational reflux and chylous edema of the lower limb and external genitalia especially if a surgical intervention is proposed.11, 12 In this examination, ultrafluid “Lipiodol” is injected into a lymphatic collector, isolated with a microsurgical technique, on the dorsum of the both feet. This type of investigation is minimally invasive and, if performed according to well-established standards, has minimal complications. Rare adversereactionsincludepulmonarymicroembolism,especiallyinthepresenceofperipheral lymphovenous fistulas, or contrast allergy. Infection at the site of skin incision, acute lymphangitis and lymphorrhea may also occur. Direct lymphangiography can also be performed in children. It enables a morphological and functional study of the superficial and the deep lymphatic circulations to take place.12

Computer tomography (CT), ultrasonography, and lymphangio-MRI may also provide information on lymphatic and chylous dysfunction. Indirect lymphangiography13 is per- formedusingadermo-hypodermicinjectionofawater-solublecontrastmedium(“Iotasul”) and is useful to clarify aetio-pathological aspects of primary lymphoedemas. Fluorescent micro-lymphography14 can be helpful in assessing the status of the superficial dermal lymphatics, which reflects peripheral lymphatic function. The conventional HoudackMcMaster dye test with the injection of a highly lymphotropic vital stain (Patent Blue V) is used today as a rapid preliminary investigation before direct lymphangiography and microsurgery. Recent studies by Olszewski15 and Campisi et al.16 have developed a system

to measure endolymphatic pressure and lymphatic flow rate. These parameters, together with a venous pressure assessment, help to measure the lymph-venous pressure gradient which is essential prior to microsurgical treatment. With this method, a lymphatic vessel is isolated and cannulated at the lower third of the leg’s medial surface. Changes in the flow and pressure can be recorded during microsurgery, elevation and dependency, at rest and under dynamic conditions. These studies have shown that a lymphatic-venous pressure gradient is essential to achieve good medium and long term results after microsurgery. [Q2:B,C,E]

Manual lymphatic drainage has been shown to be a highly effective treatment in the conservative management of lymphoedema.17–19 This followed by the application of bandaging and eventually graded compression stockings. The use of intermittent compression pneumatic devices is usually complementary to manual lymphatic drainage and may contribute to further reduction of the lymphoedema. Pharmacotherapy includes the use of antibiotics, particularly penicillin,20 anti-inflammatory drugs, and benzopyrones.21 The positive effect of benzopyrones was described by Casley-Smith et al.,21 but their role in the treatment of lymphoedemas has yet to be clarified.

Thirty years ago, only the most severe cases of elephantiasis were treated surgically, mainly to achieve a reduction in volume. The most popular surgical methods were those proposed by Charles22 (total resection of skin-lipid layers), Thompson23 (drainage with scarred subfascial skin flap), and Servelle24 (total surface lymphangectomy). They were highly destructive and invasive operations and as such they could not be recommended in less advanced or initial stages or in childhood disease.25 More recently, microsurgical lym- phatic-venous and lymph node-venous anastomoses were introduced for the management of lymphoedema resistant to conservative treatment.26, 27 These techniques are beneficial in secondary, as well as primary lymphoedemas.28 Early intervention is possible, even in children, where lymphatic-capsule-venous anastomoses are preferred.29

Lymphostatic disease may be associated with venous impairment such as varices, superficial thrombophlebitis, deep venous thrombosis and post-phlebitic sequelae. These conditions are a contraindication to traditional lymphatic-venous anastomoses. Novel reconstructive lymphatic surgery techniques however provide hope for these patients.30 This includes segmental autotransplantation of lymphatic collectors31 for the treatment of unilateral lymphoedema or the personally described method of interposition autologous venous grafting or lymphatic-venous-lymphatic plasty.32

The clinical use of microvascular lymphatic or lymph nodal flaps33, 34 is still under evaluation. They may provide future treatment options in refractory secondary lymphoedema and for the primary lymphoedemas which cannot benefit from microsurgical techniques.

Elasticstockingsareusuallywornforanaverageperiodof1–5yearsaftermicrosurgery according to the stage of the pathology at the time of operation. The stockings aim to prevent the closure of anastomoses because a rapid reduction of edema, pressure and flow is expected as a result of the improved drainage.35 [Q3:A,B,D]

Patients are followed up at 1, 3, 6 and 12 months post surgery and then annually for 5 years. Lymphatic microsurgery results in improvement in more than 80% of cases. Better outcomeshavebeenobservedinpatientsundergoingprophylacticmicrosurgery(atstagesII

Lymphoedema Staging

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 immuno-histochemical 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.

Fig. 54.7  Recent clinical staging of lymphoedema, including functional disability and pathological findings

and III; see Fig. 54.7). The frequency of lymphangitic attacks also decreases. The reduction in edema volume is seen within the first three postoperative days, and a further decrease is observed between the first and fifth years after operation. From the fifth year onwards, the clinical condition of the limb tends to remain static and this effect is maintained for more than10yearsaftersurgery.Lymphangioscintigraphyprovidesevidencethattheflowthrough the venous grafts parallels the clinical improvement.36[Q4:A,C]

Early identification, diagnostic lymphangioscintigraphy37 and prophylactic treatment of high risk patients has been suggested as a means of preventing secondary lymphoedema.38, 39 These include patients undergoing oncological lymphadenectomies, particularly in combination with radiotherapy. Microsurgery is a reasonable option on lymphoedemas that are expected to show unrelenting progression.40 The Arm Reverse Mapping (ARM) technique allows the precise identification of arm lymphatics and lymph nodes. Selective preservation is therefore possible but at a risk of leaving behind undetected metastatic disease. Since both arm lymphatics and breast efferents drain into the common axillary basin, its removal may interrupt the lymphatic flow from the arm. If a microsurgical lymphaticvenous anastomosis (LVA), is performed immediately after nodal excision this problem maybeavoided.ALVAisasurgicaltechniqueproposedforselectedpatientswithoperable­ breast cancer requiring an axillary dissection. Blue dye is injected into the arm lymphatics and a simultaneous LVA is then performed between these and an axillary vein branch (Lymphatic Microsurgical Preventive Healing Approach – LY.M.P.H.A.) (Fig. 54.8).41

[Q5:B,C]