Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

BACKGROUND: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. METHODS: Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. RESULTS: Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. CONCLUSION: Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. REGISTRATION NUMBER: ISRCTN84866416 ( http://www.isrctn.com).

Diagnosis and therapy in children with lymphoedema.

INTRODUCTION: Lymphoedema (LE) is a disorder characterized by persistent swelling caused by impaired lymphatic drainage because of various aetiologies, including lymphatic injury and congenital functional or anatomical defects. OBJECTIVE: Literature review and expert opinion about diagnosis and treatment of LE in children. RESULTS: LE is rare in children, with a prevalence of about 1.15/100,000 persons, 20 years old. The management of LE in children differs considerably from adults in terms of origin, co-morbidity and therapeutic approach. The objective of this presentation is to discuss practical issues related to clinically relevant information on the diagnosis, aetiology, work-up and treatment of LE in children. In contrast to adults, who usually experience secondary LE because of acquired lymphatic failure, most cases in children have a primary origin. The diagnosis can be made mainly on the basis of careful personal and family history, and physical examination. LE in children can be part of a syndrome if there are other concomitant phenotypic abnormalities and if a genetic defect is recognizable. Treatment of LE is mostly conservative utilizing decongestive LE therapy including compression therapy, directed exercises, massage and skincare. In the neonate, initial observation alone may be sufficient, as delayed lymphatic development and maturation can result in spontaneous improvement. The role of parents is crucial in providing the necessary input. CONCLUSION: We present a review emphasizing a practical approach to treating a child with LE according to current publications and our own experience.

In vivo quantification of the structural abnormalities in psoriatic microvessels before and after pulsed dye laser treatment.

BACKGROUND: Microvascular abnormalities (capillary elongation, widening and tortuosity) are a characteristic feature of psoriasis and form one of the pathological diagnostic criteria. These changes occur early in the progression of a psoriatic plaque, before there is clinical or histological evidence of epidermal hyperplasia. Treatment of psoriatic microvessels with a pulsed dye laser (PDL) has been associated with both clinical improvement and clearance of lesions. OBJECTIVES: To quantify the structural vascular abnormalities in plaque skin using noninvasive techniques in vivo. Investigations were carried out before and after PDL treatment to determine the nature of laser-induced microvascular changes and the relationship between these changes and clinical improvement. METHODS: Plaque microvessels were visualized using native capillaroscopy. Plaques were then treated three times with the PDL at 14-day intervals. Native capillaroscopy was repeated at 2 and 6 weeks after the final laser treatment. Images were analysed using a combination of nonstereological and stereological measurements. RESULTS: Whole body disease was stable. Treated plaques showed a 48% reduction in plaque severity score (P < 0.01). Native studies showed that the PDL significantly reduced plaque microvessel density (P < 0.05), image area fraction (P < 0.01), microvessel length density (P < 0.01) and vessel image width (P < 0.01). The reduction in plaque severity score (which denoted clinical improvement) was related quantitatively to the reduction in microvessel area per unit area of plaque skin, i.e. the image area fraction (correlation coefficient = 0.772, P < 0.01). The greatest response of plaque microvessels was within 2 weeks after the final laser treatment, while the greatest reduction in plaque severity score occurred between 2 and 6 weeks after the final laser treatment, i.e. clinical improvement was preceded by microvascular improvement. CONCLUSIONS: These findings indicate that there is a close correlation between the state of the superficial vasculature and the clinical status of psoriasis. The expanded superficial microvascular bed in plaque skin is a necessary component for maintaining clinical lesions and these blood vessels are thus a legitimate target for treatment.

A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema.

This paper describes a randomized controlled crossover study examining the effects of manual lymphatic drainage (MLD) in 31 women with breast cancer-related lymphoedema. MLD is a type of massage used in combination with skin care, support/compression therapy and exercise in the management of lymphoedema. A modified version of MLD, referred to as simple lymphatic drainage (SLD), is commonly taught as a self-help measure. There has been limited research into the efficacy of MLD and SLD. The study reported here explores the effects of MLD and SLD on a range of outcome measures. The findings demonstrate that MLD significantly reduces excess limb volume (difference, d=71, 95% CI=16-126, P=0.013) and reduced dermal thickness in the upper arm (d=0.15, 95% CI=0.12-0.29, P =0.03). Quality of life, in terms of emotional function (d=7.2, 95% CI=2.3-12.1, P=0.006), dyspnoea (d=-4.6, 95% CI=-9.1 to -0.15, P=0.04) and sleep disturbance (d =-9.2, 95% CI=-17.4 to -1.0, P=0.03), and a number of altered sensations, such as pain and heaviness, were also significantly improved by MLD. The study provides evidence to support the use of MLD in women with breast cancer-related lymphoedema. The limitations of the study are outlined and future areas for study are highlighted.

A randomized, controlled, parallel-group clinical trial comparing multilayer bandaging followed by hosiery versus hosiery alone in the treatment of patients with lymphedema of the limb.

BACKGROUND: Multilayered, low stretch bandages (MLB) combined with exercises, skin care, and manual lymphatic drainage therapy are recommended as an intensive phase of treatment for lymphedema patients. The relative efficacy of each of the components of this comprehensive treatment program have not been determined. This study aimed to compare the effect of multilayer bandaging as an initial phase of lymphedema treatment followed by elastic hosiery versus hosiery alone. METHODS: A randomized, controlled, parallel-group trial was undertaken in the setting of the Lymphedema Clinic, The Royal Marsden Hospital, London. Ninety women with unilateral lymphedema (of the upper or lower limbs) were enrolled in the study. The interventions consisted of 18 days of multilayer bandaging followed by elastic hosiery or hosiery alone, each for a total period of 24 weeks. The main outcome measure was the percentage reduction in excess limb volume. RESULTS: The reduction in limb volume by MLB followed by hosiery was approximately double that from hosiery alone and was sustained over the 24-week period. The mean overall percentage reduction at 24 weeks was 31% (n = 32) for MLB versus 15.8% (n = 46) for hosiery alone, for a mean difference of 15. 2% (95% confidence interval, 6.2-24.2) (P = 0.001). CONCLUSIONS: Multilayer bandaging as an initial phase of treatment for lymphedema patients, followed by hosiery, achieves greater and more sustained limb volume reduction than hosiery alone.

Chronic arm edema following breast cancer treatment.

Chronic edema of the arm (postmastectomy edema, PME) is a common and incurable complication of breast cancer treatment, often developing without warning months or years later. Although the original cause of PME is damage to axillary lymph drainage routes by surgery and radiotherapy, many observations suggest that additional factors are involved. Recent attention has focused on the Starling forces in the skin and subcutis in PME. An important finding was that the protein concentration, and hence colloid osmotic pressure, of the subcutaneous interstitial fluid of the PMF arm is unexpectedly lower than in the unaffected arm, correlating negatively with the degree of swelling. There are several possible explanations for this, such as a rise in capillary filtration rate, or interstitial proteolysis. A systemic component to PME is suggested by the finding of a lower plasma protein concentration in affected women compared with a matched postmastectomy group without swelling. A recent study using intra-vital capillaroscopy has indicated that angiogenesis occurs in the skin in PME, and an increased capillary surface area for filtration could result in an increased fluid load on a compromised lymph drainage system. Further elucidation of the pathophysiological processes in PME, in particular the adjustments to Starling forces, will enable more effective therapy of this distressing condition.

Therapy approaches for lymphedema.

Lymphedema, regardless of etiology, is essentially incurable but different therapy approaches exist which serve to contain swelling. The objectives of treatment are to reduce swelling, restore shape, and prevent inflammatory episodes, eg, recurrent cellulitis. There are essentially three main approaches to lymphedema treatment: physical therapy, drug therapy, and surgery. Any edema arises from an imbalance between capillary filtration and lymph drainage. The principle of physical therapy is to a) reduce excessive capillary filtration and b) improve drainage of interstitial fluid and macromolecules from congested regions to normally draining lymph node sites. This is achieved through a combination of compression, exercise, and if possible, massage. Control of recurrent inflammatory episodes can only be achieved through diabetic type skin care, a reduction in swelling, and if necessary, prophylactic antibiotics. Drug therapy comprises diuretics or the coumarin/flavonoid group of drugs. The use of diuretics for pure lymphedema is physiologically unsound but may be of use in edema of mixed origin and in palliative (cancer) circumstances. Coumarin/flavonoids have been shown to reduce swelling in all types of lymphedema. Surgery is indicated at an early stage for facial swelling, where vision is compromised, or genital lymphedema, where genitourinary function is affected. Otherwise, reducing operations should only be performed when alternative therapy has failed. Microsurgery for certain forms of lymphedema continues to be evaluated.