Therapy of peripheral lymphedema is divided into conservative (non-operative) and operative methods.
Treatment of lymphedemas
- Physical therapy
- Combined Physical Therapy
- Compression therapy
- Manual lymph-drainage
- Antimycotic drugs
- Derivative surgery
- Reconstructive surgery
1 – Combined Physical Therapy (CPT). This methodology generally involves a two-stage treatment program: the first phase consists of skin care, manual lymphatic drainage, range of motion exercise and compression, typically applied with multi-layered bandage wrapping. Phase 2 (initiated promptly after Phase 1) aims to maintain and optimize the results obtained in Phase 1. It consists of skin care, compression by a low-stretch elastic stocking or sleeve, continued “remedial” exercise, and repeated manual lymphatic drainage, as needed. Prerequisites of successful combined physiotherapy are the availability of physicians (i.e., clinical lymphologists), nurses, and therapists highly trained and educated in this method. Compressive bandages, when applied incorrectly, can be harmful and/or useless. A prescription for low stretch elastic garments (custom-made with specific measurement, if needed) to maintain lymphedema reduction after CPT is essential for long-term care.
2 – Uniform and/or Intermittent Pneumatic Compression. Pneumomassage is usually a three-phase program: treatment of lymph nodes proximal to the extremity, to prepare them and avoid engorgement; external compression therapy, using appropriate pressure values depending on the clinical stage of lymphedema; compression stockings or sleeves or multilayered bandaging are then used to maintain edema reduction.
3 – Manual Lymph-drainage. Mostly performed according to the conventional methods of the German and Belgian schools. The various massage techniques may also be combined, on a case-by-case approach. Not to be performed too vigorously, in order to avoid damage to lymphatic vessels and lymph nodes.
Benzopyrones (b.): these drugs include Coumarine and its derivatives (alpha-B.) and Bioflavonoids and their derivatives (gamma-b., Diosmine, Rutine, Esperidine, Quercetine, etc.).
Alpha-b. act as follows:
- Increase capillary tone
- Reduce capillary permeability to proteins
- Increase the number of macrophages
- Promote macrophage proteolytic action
- Stimulate lymphangion propulsion action
- Inhibit prostaglandin and leukotriene synthesis
Therefore, their effects are as follows:
- Interstitial fluid reabsorption
- Gradual regression of fibrosis promoted by macrophage proteolysis
- Reduction of chronic inflammation with subsequent lower incidence of acute episodes and less tendency to fibrotic edema development.
Natural Coumarines, to be administered in 8 mg/die dosage for 60 days, have shown to be therapeutically effective in improving subjective symptoms, in functional recovery of the lymphedematous extremity, in reducing edema thickness, promoting bulk reduction after physical and/or microsurgical treatment, without toxic effects to the liver.
Gamma-b actions include the following:
- Reduction of endothelium permeability to protein macromolecules
- Capillary filtration reduction
- Venule tone increase.
Hence, its effects are as follows:
- Stabilizing action on interstitial connective tissue and on the capillary wall
- Prostaglandin and leukotriene production inhibition.
- Antibiotics: antibiotics are used during the acute phase (beta-hemolytic streptococcus therapy), for treating dermatolymphangio-adenitis (DLA), and as a preventative prophylactic treatment against acute lymphangitis episodes (slow-release penicillin).
- Antimycotic drugs: they are used to treat fungal infection of the extremities (flucanozole, etc.).
- Dietylcarbamazine: they are used to eliminate microfilariae from the bloodstream in patients with lymphatic filariasis and also for healthy carriers.
- Diuretics: normally prescribed at low dosages and for short periods, specially when lymphedema is associated with phlebedema or other disorders such as heart and kidney disease, ascites, chyliferous vessels disorders, etc.
- Diet: in obese patients, reducing caloric intake combined with a supervised exercise program is of distinct value in decreasing limb bulk. Restricted fluid intake is not of demonstrated benefit. In chylous reflux syndromes, a diet low in lipids and the exclusive intake of medium-chain triglycerides (MCT), which are absorbed via the portal vein, without overloading the chyliferous vessel system, has proved to be of great benefit, especially in children.
Therefore, there is a wide range of pharmacologic and therapeutic principles available. Which one is to be selected depends on etiopathogenic and physiopathologic features of each type of lymphedema.
Surgical techniques employed in the past to treat lymphedema would focus on bulk reduction of the affected limbs by a debulking-resective operation (cutolipofascectomy, total surface lymphangectomy). However, these were only symptomatic treatments: since they would not remove the cause of lymph flow obstruction, they were reducing lymphedema only temporarily, with subsequent recurring lymphedema, which would spread unevenly in the affected extremity due to retracting and disfiguring scars.
Following the advent of Microsurgery, functional and causal therapeutic solutions for lymphedema were investigated and implemented aiming at draining the lymph flow or reconstructing the lymphatic pathways, where they had been obstructed or were missing. Fine, repairing techniques were employed with direct intervention on the very lymphatic structures.
Indications for Lymphatic Microsurgery
- Initial stages (IB, II, early III) – with reference to the 5-stage classification reported in the guidelines of Società Italiana di Linfangiologia
- Lymphoscintigraphy showing reduced proximal lymph node uptake, and minimum or no tracer flow beyond a specific lymph node
- Excellent patient’s compliance
- Referral Lymphology Centre the patient can report if necessary, in addition to the Lymphatic Surgery centre where he /she has been operated upon.
- Advance stages (III advance, IV and V)
- Lymphoscintigraphy showing no tracer upflow (“mute scintigraphy”)
- Poor patient’s compliance
- Lymphatic-lymph node aplasia (extremely rare)
- Diffuse metastatic disease
- Advance Stage (V), with poor response to conservative treatment
Microsurgery techniques have yielded positive and long-lasting results in the treatment of primary lymphedemas - including those in children -, as well as in secondary lymphedemas following cancer treatment, involving lymph node resection in some 'critical' areas, such as in the armpits and the groin.
Lymphatic Microsurgery: derivative and reconstructive microsurgery.
Microsurgical Techniques developed for a “conservative and functional” treatment of lymphedema can be distinguished into derivative and reconstructive.
Derivative microsurgery techniques aim to resume lymph flow at the obstruction site, through a lymph-venous drainage in which lymph nodes or, directly, lymphatics are employed:
- Lymph node-Venous Anastomosis (LNVA)
- Lymphatic-Capsular-Venous Anastomosis (LCVA)
- End-to-end Lymphatic - Venous Anastomosis (EE-LVA)
- End-to-side Lymphatic - Venous Anastomosis (ES-LVA)
The anastomosis of a lymph node - following its either cross or longitudinal cut – with a major vein of either the superficial or deep venous circulation in the extremity affected by lymphedema shortly tends to become obstructed due to venous thrombosis at the site of the anastomosis, or because of endothelialization of the anastomotic lymph node surface. Lymphatic-Capsular-Venous Anastomosis is thus preferably employed to treat lymphedema in children, in order to avoid excessive trauma to the small veins selected for the anastomosis. This method features the anastomosis of the lymph node capsular segment, together with afferent lymphatic collectors, to the satellite vein. End-to-end Lymphatic - Venous Anastomosis is performed with a telescopic technique, by applying one single U stitch. This technique is adopted when the gap between lymphatic collectors and the vein to be anastomized is such that no stress-free anastomosis would be feasible. Therefore, in these cases, a continent collateral vein of the major vein is employed for End-to-end Lymphatic - Venous Anastomosis (Figures 1,2).
Figure 1,A-B Multiple End-to-end Lymphatic - Venous Anastomosis–with telescopic technique, following anastomosis of lymphatic collectors into the venous segment.
Figure 2 Derivative lymphatic-venous microsurgery in brachial region for the treatment of upper limb lymphedema (the median nerve and the brachial artery can be seen).
End-to-end Lymphatic - Venous Anastomosis is best performed with Degni’s grooved needle. The lower flap of the lymphatic segment wall is put inside the vein with an end-to-side arrangement, thus acting as a valve to prevent blood reflux into the lymphatic collector. This technique was later modified (Campisi, 1989), by using the outlet of a collateral vein of the major vein as venous access for lymphatic collectors. With this technical expedient - owing to smooth muscle cells arrangement in the venous wall at the point of entry of lymphatic collectors –, there is no risk of stenosis of the anastomosis.
With reconstructive microsurgery techniques, the lymphatic flow is resumed by overcoming the obstruction site, through the implant of autologous or venous segments between collectors down and upstream the obstruction:
- Lymphatic-Lymphatic Anastomosis (LLA)
- Segmental Lymphatic Vessel Autotransplantation (SLAT)
- Lymphatic-Venous-Lymphatic-Plasty or Lymphatic-Venous-Lymphatic Anastomosis (LVLA).
- Free Lymphatic- Lymph Nodal Flaps (FLF)
Lymphatic-lymphatic anastomosis is rarely employed, because the gap between afferent and efferent collectors is often too wide to fashion a direct anastomosis. Hence, the interposition of a lymphatic segment or a vein is often required. Lymphatic collector self-transplantation is a time-consuming technique, which allows only 1 or 2 lymphatic pathways of the affected extremity to be reconstructed. It can be applied exclusively in the treatment of monolateral lymphedemas, since the lymphatic segment is harvested from the healthy side, with a surgical resection, which, being relatively extensive, could in turn be the cause of iatrogenic lymphedema. The interposition of autologous venous grafts between lymphatic collectors upstream the lymphatic flow obstacle is another, easy to perform method, alternative to derivative microsurgery (Campisi, 1982).
Venous grafts are easily harvested from the same site of surgery, from the volar surface of the forearm or the leg (collateral branches of the saphena veins), with a length from 7 to 25 cm and a gauge of 1.5-5 mm. This method is mostly used for the lower limbs. The site of operation is the supra or sub-inguinal region; a telescopic anastomosis is fashioned, with a U stitch in non-resorbable nylon, monofilament, 8/0 material. A Lymphatic-Venous-Lymphatic Anastomosis (LVLA) takes 2 and a half hours on average to complete, and it is normally applied in cases of venous disease (e.g. venous hypertension, valvular insufficiency) that cannot be surgically treated (Figure 3).
Figure 3, A-C: Schematic drawing and intra-operative phases of a reconstructive Lymphatic-Venous-Lymphatic Microsurgery, with interposition of autologous venous segment between lymphatic collectors downstream and upstream the obstacle.
In cases of severe lymphatics-lymph node hypoplasia, free lymphatics-lymph node flaps can offer a good solution, featuring a free microvascular self-transplantation of lymphatic-lymph node tissue in the axillary or inguinal region of the affected extremity.
Microsurgical Techniques for lymphostasis treatment boast a good success rate, with 50% to 75%, and up to 100% reduction in edema thickness and volume in the affected extremity from pre-treatment conditions, depending on disease stage: the earlier the treatment, the higher the percentage in edema regression. Stable and longlasting results have been reported in follow-up studies after 15 years from surgery of patients treated for limb lymphedema with Lymphatic Microsurgery. Treatment outcome is assessed based on water volumetry and lymphatic scintigraphy performed before treatment and at various intervals from surgery.
Medium and long term outcome assessment
Treatment outcome is assessed with volumetry and lymphatic scintigraphy. As to volume measurement of the affected extremity, a water volumeter is employed, featuring a cylinder with known surface, filled with water, and communicating with a graduated column in transparent material, where the limb is introduced. Volume changes of the limb are measured against the amount of displaced water. In cases of lymphedema affecting only one extremity, the measurements are compared to the healthy limb. Alternatively, the truncated cone formula can be applied and the limb volume measured by taking the limb circumference.
With lymphatic scintigraphy (Figure 4), performed at various intervals from surgery, the patency of derivative or reconstructive microsurgical anastomoses can be assessed by 1) showing dermal backflow reduction, 2) tracer disappearance at the level of the micro-anastomoses due to blood flow, 3) early liver "uptake" of the tracer, which is indicative of a faster flow of tracer into systemic circulation, 4) resumption of preferential lymphatic pathways with tracer upflow, 5) display of the interposed venous segment.
Figure 4: Lymphoscintigraphy before and after derivative lymphatic-venous microsurgery - in 1/3 midportion of the forearm volar surface. Development of a preferential lymphatic drainage pathway can be observed, together with dermal back flow reduction, and early liver uptake of tracer.
Figure 5: 3rd stage upper limb lymphedema, secondary to breast cancer treatment, before and after microsurgery.
Figure 6: 3rd stage lower limb primary lymphedema, before and after derivative lymphatic-venous microsurgery.
Figure 7: Congenital, 4th stage lymphedema of the lower limbs, caused by gravitational reflux, in a child, before and one week after bilateral derivative lymphatic-venous microsurgery in the inguinal-crural region.
Figure 8: Lower limb lymphedema treated with reconstructive microsurgery with bilateral lymphatic-venous-lymphatic plasty in the inguinal region.
Figure 9, A-B: Elephantiasis of right lower limb, in obese patient, treated with CDP (combined decongestion) and lymphatic-venous derivative microsurgery, in association with appropriate obesity treatment.
Rational of integrated therapeutic protocol:
- By-pass of obstruction site by lymphatic-venous drainage, upstream the obstacle, or by a venous “bridge” between lymphatics upstream and downstream the obstacle
Initial treatment always includes CDP, possibly conducted at specialist centers by expert personnel skilled in the treatment of lymphologic diseases
Surgical timing: application of microsurgical techniques, as soon as conservative treatment, after achieving a more or less significant edema reduction, fails to further improve the clinical picture or to keep in check lymphangitis attacks.
At this point, microsurgery allows a further enhancement of the results obtained with conservative treatment, which will be applied again after surgery, in order to stabilize the outcome obtained with surgery, as well as to improve it with time. With microsurgery, not only secondary, but also primary lymphedemas can be treated, which, in the majority of cases, are due to congenital lymph circulation obstruction, due to proximal (axillary or inguinal) lymph node fibrosclerosis, and with lymphatic collectors, afferent to the same lymph nodes, that are working normally, but are often dilated and hypertrophic, due to extra efforts involved in overcoming the obstacle. Microsurgical techniques allow to divert the lymphatic flow, which is obstructed out of either congenital or acquired reasons, into the venous circulation, if the latter is in good conditions, or, where there is the blockage, to reconstruct a connection pathway between lymphatic collectors upstream and downstream the obstacle, through the interposition of lymphatic segments or, even better, autologous venous grafts (lymphatic-venous-lymphatic plasty). Finally, microsurgical techniques play a key role in secondary lymphedema prevention, as well as in preventing disease progression and complications (lymphangites, lymphorrhoea, lymphostatic verrucosis and, in more advanced stages, the onset of lymphangiosarcoma). Complementary and alternative therapies of lymphedema are to be identified with disease prevention possibilities, in particular, with regard to upper limb lymphedema secondary to breast cancer surgery and/or radiation therapy. Prevention is based on lymphoscintigraphy, which – both before and after tumor treatment involving the breast as well as axillary lymph nodes – permits to study the anatomic-functional lymph flow system in the homolateral arm. In this way, it is thus possible to identify patients at (low, medium, or high) risk of secondary lymphedema onset. Therefore, these patients could successfully benefit from early – rather than late – therapeutic measures, which best suit them on a case-by-case basis, depending on the identified extension of lymph flow damage.