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      Non-surgical Treatments of Lymphedema of the Lower Limbs Translated title: Tratamento médico do linfedema dos membros inferiors

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          Abstract

          Background: LLL is characterized by protein-rich interstitial fluid accumulation due to lymphatic system insufficiency, resulting in progressive non-pitting edema. Primary and secondary lymphedema are distinguished by the absence or presence of an external trigging factor, respectively. Diagnosis is based on clinical examination combined with imaging modalities. The non-surgical approach of LLL is based on preventive measures, lifestyle interventions and life-long compression modalities, aiming to reduce the edema congestion and to improve patient quality of life. Objectives: The present literature review aims to compile current scientific knowledge on the various domains of the non-surgical treatments of LLL. Methods: Search was performed in PubMed database, using the following medical subjects heading (MeSH) terms: “lymphedema”, “lower limbs” and “medical treatment”. Research and review articles indexed in the last 10 years and written in English language were selected. Animal experimentation works and single case-reports were excluded. Other materials searched comprised reference books in the area of Vascular Surgery, namely Rutherford Vascular Surgery - 9th Edition, 2018. Development: The non-surgical treatment of LLL is characterized by a multifaceted approach, including mechanical reduction of limb swelling, alternative medical devices and pharmacological therapy. Complex decongestive therapy is recognized as the standard of treatment and its compression modalities include drainage massages, pneumatic compression, bandaging systems, compression garments and physical exercise. Compression therapies differ in the degree and time of pressure applied and can be performed by healthcare professionals or by the patient himself. The duration of treatment stages varies and it may include hospital and outpatient regimens. Positive treatment outcomes include increased skin elasticity, limb volume reduction, pain relief, increased functional capacity and improved quality of life. Conclusions: Compression modalities have been shown to be effective in reducing limb volume, increasing tissue elasticity and improving the physical, psychological and aesthetic aspects of patient life. However, sustained volume reductions depend mostly on patient diligence. Intensive and outpatients approaches do not compromise treatment efficacy and high pressures therapies are effective and well tolerated. Current lymphedema non-surgical treatment lacks long-term results and urges more effective therapeutic alternatives.

          Translated abstract

          Introdução: O linfedema dos membro inferior é caracterizado pela acumulação de líquido intersticial rico em proteínas consequente a uma insuficiência do sistema linfático, resultando em edema progressivo e não depressível do membro inferior. Há 2 tipos de linfedema primário e secundário. O primeiro sem etiologia conhecida. O diagnóstico é feito através da avaliação clínica em combinação com modalidades de imagem. O tratamento médico do linfedema dos membros inferiores é baseado em medidas preventivas, alterações do estilo de vida e modalidades de compressão contínuas, com o objetivo de reduzir a congestão do edema e melhorar a qualidade de vida dos doentes. Objetivos: A presente revisão literária tem como objetivo compilar o conhecimento científico atual acerca dos diversos domínios do tratamento médico do linfedema dos membros inferiores. Metodologia: A pesquisa foi realizada na base de dados do PubMed, utilizando os seguintes termos médicos (MeSH): “lymphedema”, “lower limbs” e “medical treatment”. Foram selecionados artigos de investigação e de revisão indexados nos últimos 10 anos e escritos em inglês. Os projetos de experimentação animal e relatos de caso clínico isolado foram excluídos. Outros materiais pesquisados incluíram livros de referência na área de Cirurgia Vascular, nomeadamente Rutherford Vascular Surgery - 9ª Edição, 2018. Desenvolvimento: O tratamento médico do linfedema dos membros inferiores é caracterizado por uma abordagem multifacetada, que inclui a redução mecânica do edema dos membros, dispositivos médicos alternativos e terapia farmacológica. A terapia descongestiva complexa é considerada o tratamento padrão e suas modalidades de compressão incluem massagens manuais de drenagem, compressão pneumática, sistemas de bandagem, vestuário de compressão e exercício físico. As terapias de compressão diferem no grau e tempo de pressão aplicados e podem ser administradas por profissionais de saúde ou pelo próprio doente. A duração das fases do tratamento é variável e este pode incluir regimes hospitalares e em ambulatório. Os resultados positivos do tratamento incluem o aumento da elasticidade da pele, a diminuição do volume do membro, a redução da dor, o aumento da capacidade funcional e a melhoria da qualidade de vida. Conclusões: As modalidades de compressão demonstraram ser eficazes na redução do volume dos membros, aumentando a elasticidade dos tecidos e melhorando os aspetos físicos, psicológicos e estéticos da vida do doente. No entanto, a manutenção das reduções de volume dependem principalmente da aderência ao tratamento por parte do doente. As abordagens intensivas e em regime de ambulatório não comprometem a eficácia do tratamento e as terapias de alta pressão são eficazes e bem toleradas. O atual tratamento médico do linfedema carece de resultados a longo prazo e necessita de alternativas terapêuticas mais eficazes.

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          Compression for venous leg ulcers.

          Up to one percent of people in industrialised countries will suffer from a leg ulcer at some time. The majority of these leg ulcers are due to problems in the veins, resulting in an accumulation of blood in the legs. Leg ulcers arising from venous problems are called venous (or varicose or stasis) ulcers. The main treatment is the application of a firm compression garment (bandage or stocking) in order to aid venous return. There is a large number of compression garments available and it was unclear whether they are effective in treating venous ulcers and, if so, which method of compression is the most effective. To undertake a systematic review of all randomised controlled trials (RCTs) evaluating the effects on venous ulcer healing of compression bandages and stockings.Specific questions addressed by the review are:1. Does the application of compression bandages or stockings aid venous ulcer healing? 2. Which compression bandage or stocking system is the most effective? For this second update we searched: the Cochrane Wounds Group Specialised Register (31 May 2012); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 5, 2012); Ovid MEDLINE (1950 to May Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 30 May 2012); Ovid EMBASE (1980 to 2012 Week 21); and EBSCO CINAHL (1982 to 30 May 2012). No date or language restrictions were applied. RCTs recruiting people with venous leg ulceration that evaluated any type of compression bandage system or compression stockings were eligible for inclusion. Eligible comparators included no compression (e.g. primary dressing alone, non-compressive bandage) or an alternative type of compression. RCTs had to report an objective measure of ulcer healing in order to be included (primary outcome for the review). SECONDARY OUTCOMES of the review included ulcer recurrence, costs, quality of life, pain, adverse events and withdrawals. There was no restriction on date, language or publication status of RCTs. Details of eligible studies were extracted and summarised using a data extraction table. Data extraction was performed by one review author and verified independently by a second review author. Forty-eight RCTs reporting 59 comparisons were included (4321 participants in total). Most RCTs were small, and most were at unclear or high risk of bias. Duration of follow-up varied across RCTs. Risk ratio (RR) and other estimates are shown below where RCTs were pooled; otherwise findings refer to a single RCT.There was evidence from eight RCTs (unpooled) that healing outcomes (including time to healing) are better when patients receive compression compared with no compression.Single-component compression bandage systems are less effective than multi-component compression for complete healing at six months (one large RCT).A two-component system containing an elastic bandage healed more ulcers at one year than one without an elastic component (one small RCT).Three-component systems containing an elastic component healed more ulcers than those without elastic at three to four months (two RCTs pooled), RR 1.83 (95% CI 1.26 to 2.67), but another RCT showed no difference between groups at six months.An individual patient data meta-analysis of five RCTs suggested significantly faster healing with the four-layer bandage (4LB) than the short stretch bandage (SSB): median days to healing estimated at 90 and 99 respectively; hazard ratio 1.31 (95% CI 1.09 to 1.58).High-compression stockings are associated with better healing outcomes than SSB at two to four months: RR 1.62 (95% CI 1.26 to 2.10), estimate from four pooled RCTs.One RCT suggested better healing outcomes at 16 months with the addition of a tubular device plus single elastic bandage to a base system of gauze and crepe bandages when compared with two added elastic bandages. Another RCT had three arms; when one or two elastic bandages were added to a base three-component system that included an outer tubular layer, healing outcomes were better at six months for the two groups receiving elastic bandages.There is currently no evidence of a statistically significant difference for the following comparisons:⋅alternative single-component compression bandages (two RCTs, unpooled);⋅two-component bandages compared with the 4LB at three months (three RCTs pooled);⋅alternative versions of the 4LB for complete healing at times up to and including six months (three RCTs, unpooled);⋅4LB compared with paste bandage for complete healing at three months (two RCTs, pooled), six months or one year (one RCT for each time point);⋅adjustable compression boots compared with paste bandages for the outcome of change in ulcer area at three months (one small RCT);⋅adjustable compression boots compared with the 4LB with respect to complete healing at three months (one small RCT);⋅single-layer compression stocking compared with paste bandages for outcome of complete healing at four months (one small RCT) and 18 months (another small RCT);⋅low compression stocking compared with SSB for complete healing at three and six months (one small RCT);⋅compression stockings compared with a two-component bandage system and the 4LB for the outcome of complete healing at three months (one small, three-armed RCT); and,⋅tubular compression compared with SSB (one small RCT) for complete healing at three months. 4LB was more cost-effective than SSB. It was not possible to draw firm conclusions regarding other secondary outcomes including recurrence, adverse events and health-related quality of life. Compression increases ulcer healing rates compared with no compression. Multi-component systems are more effective than single-component systems. Multi-component systems containing an elastic bandage appear to be more effective than those composed mainly of inelastic constituents. Two-component bandage systems appear to perform as well as the 4LB. Patients receiving the 4LB heal faster than those allocated the SSB. More patients heal on high-compression stocking systems than with the SSB. Further data are required before the difference between high-compression stockings and the 4LB can be established.
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            A review of coumarin derivatives in pharmacotherapy of breast cancer.

            The coumarin (benzopyran-2-one, or chromen-2-one) ring system, present in natural products (such as the anticoagulant warfarin) that display interesting pharmacological properties, has intrigued chemists and medicinal chemists for decades to explore the natural coumarins or synthetic analogs for their applicability as drugs. Many molecules based on the coumarin ring system have been synthesized utilizing innovative synthetic techniques. The diversity oriented synthetic routes have led to interesting derivatives including the furanocoumarins, pyranocoumarins, and coumarin sulfamates (COUMATES), which have been found to be useful in photochemotherapy, antitumor and anti-HIV therapy, and as stimulants for central nervous system, antibacterials, anti-inflammatory, anti-coagulants, and dyes. Of particular interest in breast cancer chemotherapy, some coumarins and their active metabolite 7-hydroxycoumarin analogs have shown sulfatase and aromatase inhibitory activities. Coumarin based selective estrogen receptor modulators (SERMs) and coumarin-estrogen conjugates have also been described as potential antibreast cancer agents. Since breast cancer is the second leading cause of death in American women behind lung cancer, there is a strong impetus to identify potential new drug treatments for breast cancer. Therefore, the objective of this review is to focus on important coumarin analogs with antibreast cancer activities, highlight their mechanisms of action and structure-activity relationships on selected receptors in breast tissues, and the different methods that have been applied in the construction of these pharmacologically important coumarin analogs.
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              Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema.

              Lymphoscintigraphy has largely been performed to diagnose lymphedema. It is, however a time-consuming and expensive technique, which has not been covered by Japanese medical insurance since the year 2002. In this report we introduce a new imaging technique of fluorescent lymphography to diagnose lymphedema. Fluorescence images of subcutaneous lymphatic drainage after subcutaneous injection of indocyanine green (ICG) at the foot were obtained using a newly developed near-infrared camera system. ICG fluorescent lymphography was performed in 12 patients with secondary lymphedema and 10 healthy volunteers. The 12 patients were diagnosed with secondary lymphedema according to the medical history and lymphoscintigram, of which 11 had a history of hysterectomy with extended lymph node dissection and local radiation therapy for uterine cancer. Lymphedema developed in one patient after femorotibial artery bypass for peripheral artery occlusive disease. Four abnormal fluorescent patterns of the lymph drainage were observed in lymphedema: dermal backflow (an abnormal filling of the lymph capillaries), extended fluorescent signal at the dorsum and plantar region of the foot, dilated lymph channels with proximal obliteration, and diffuse glittering of fluorescent signals with scattered twinkling of the dye. Continuous lymph channels from the injection site of the foot to the groin were observed along the medial aspect of thigh in healthy subjects. ICG fluorescence lymphography is safe, simple, and minimally invasive. The device is portable and easy to use. The technique may be useful in clinical practice to identify presence of lymphatic disorder.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                ang
                Angiologia e Cirurgia Vascular
                Angiol Cir Vasc
                Sociedade Portuguesa de Angiologia e Cirurgia Vascular (Lisboa, , Portugal )
                1646-706X
                June 2019
                : 15
                : 2
                : 86-96
                Affiliations
                [1] Porto orgnameUniversidade do Porto orgdiv1Instituto de Ciências Biomédicas Abel Salazar
                [2] Porto orgnameCentro Hospitalar Universitário do Porto orgdiv1Serviço de Angiologia e Cirurgia Vascular
                Article
                S1646-706X2019000200006 S1646-706X(19)01500200006
                0d3568dd-ba79-4253-ab22-69fdfcd2a90e

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 10 June 2019
                : 23 August 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 93, Pages: 11
                Product

                SciELO Portugal

                Categories
                Review Article

                lymphedema,tratamento médico,membros inferiores,Linfedema,medical treatment,lower limbs

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