Relationship between lymphoscintigraphy and clinical findings in lower limb lymphedema (LO): toward a comprehensive staging.

Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.

Efficacy of BN165 (Ginkor Fort) in breast cancer related upper limb lymphedema: a preliminary study.

The purpose of this study was to determine whether BN165 (Ginkor Fort), which has been reported to alleviate symptoms of venous insufficiency, has a beneficial effect on lymphatic function or lymphedema symptoms. Using a 3-arm, double-blind, placebo-controlled design in 48 patients with upper extremity lymphedema secondary to breast cancer treatment, improvement in symptoms and signs as well as lymphoscintigraphic kinetic parameters (radiocolloid half-life and lymphatic migration speed) was assessed in response to treatment. A statistically significant effect on limb heaviness was noted. Lymphatic migration speed also demonstrated a significant increase at a dose of 2 active capsules per day but not at the 3 capsules per day dose, but lymphatic migration speed also improved in the placebo group. These findings in mechanical lymphatic insufficiency in breast cancer-related lymphedemas can be compared to the previously published clinical amelioration by BN165 of the subjective symptoms (heavy limbs) of dynamic lymphatic insufficiency in patients with venous insufficiency. Further studies are needed to define the possible role of BN165 in treating patients with lymphedema.

[Tests and imaging of the lymphatic system]. / Explorations et imagerie du système lymphatique.

Methods for lymphatic imaging are numerous and can be roughly classified as anatomic or functional studies. Direct or indirect lymphographies provide useful informations in case of lymphostasis. Contrast lymphangiography is the only anatomical method giving precise informations either on lymphatic ducts or lymph nodes. Nevertheless this invasive method is no more indicated in cases of limb edemas. Indirect lymphographies study the spontaneous lymphatic drainage of inert particles injected into the dermis. The blue dye test is the most simple and the oldest indirect lymphography used in the positive diagnosis of a lymphostasis. It has been replaced with the indirect radionuclide lymphography which give more reliable informations. Fluorescence microlymphoangiography is an atraumatic method which permits the visualization of skin lymphatics. Indirect lymphangiography with contrast medium give reliable informations on the status of the initial lymphatics and is the best imaging method to differentiate between lipedema and lymphedema. Indirect radionuclide lymphoscintigraphy is a safe, non invasive and physiological method for the assessment of the limb lymphatic system used for morphological studies and objective measurement of the peripheral lymphatic function necessary to assess the lymphatic variation under therapy (decongestive physiotherapy, surgery, drugs).

[Lymphedema of the lower limbs: CT staging]. / Lymphoedème des membres inférieurs: apport du scanner.

Routinely performed, CT is useful and reliable for staging lower limb lymphedema. We describe methods we utilized. We found in frequency order: skin thickening, subcutaneous tissues area increase in regard the safe limb, perimuscular aponevrosis thickening, fat infiltration: lines parallel to the skin, edematous areas along perimuscular aponevrosis, lines perpendicular to the skin. The lowest fat density is increased on the pathologic side. Subfascial compartment is slightly fattened. We found huge differences between primary and secondary lymphedema for the thigh. Same images may be generated by old or young lymphedema. Rarely useful for positive diagnosis, CT is indispensable for secondary lymphedema staging (initial staging or after a recent increase). It seems us indispensable for any pretherapeutic staging (whole objectively disorders, exact upper limit, infraclinic bilaterality).

[Results of a neurophysiologic consultation in patients with secondary lymphedema of the arm after breast cancer associated with neurological symptoms]. / Résultats d'une consultation neurophysiologique chez des patientes atteintes d'un lymphoedème secondaire du membre supérieur après cancer du sein et présentant des troubles neurologiques.

The aim of this study was to identify the nature of the nerve lesions found in patients with neurological complains and with lymphedema occurring after breast cancer treated by surgery and radiotherapy. Twelve patients treated in a specialised centre for lymphology had clinical and neurophysiological examinations. This study found 9 radiation-induced plexopathies, 1 neoplasic plexopathy, 2 carpal tunnel syndromes (one isolated), 1 cervical root disease and 1 normal examination. The radiation-induced plexopathy is characterised by a chronic neurogenic involvement and the presence of (motor and sensory) proximal persistent conduction blocks. This study demonstrated that it is essential to identify with electrodiagnosis the exact nature of the nerve lesion to determine the most appropriate and effective treatment.

[Computerized tomography of 150 cases of lymphedema of the leg]. / Tomodensitométrie de 150 cas de lymphoedèmes des membres inférieurs.

The aim of this work was to evaluate the usefulness of CT imaging to stage lower limb lymphedemas. Between 1992 and 1997, we studied 150 cases of lymphedema, half idiopathic and half secondary. Methods used are described. In decreasing order of frequency, we found: skin thickening, increased subcutaneous tissue surface area compared with the healthy limb, thickening of the perimuscular aponevrosis, fat infiltration: lines parallel to the skin (parallel), edematous areas along the perimuscular aponevrosis, lines perpendicular to the skin (perpendicular). The lowest fat density was increased on the diseased side. The subfascial tissue showed some fat accumulation. These results were compared with findings reported in the literature. There were very major differences between idiopathic lymphedema and secondary lymphedema of the thigh. Similar images were generally generated by new and long-standing lymphedema. Rarely useful for positive diagnosis, CT is indispensable for establishing stage initially or after recent increase and, in our opinion, is essential for pretherapeutic assessment. The CT-scan gives objective evidence of overall disorders, the exact upper limit of the lymphedema, and sometimes reveals infraclinical bilateral involvement.

Lymphedematous skin and subcutis: in vivo high resolution magnetic resonance imaging evaluation.

Physico-chemical and morphologic parameters of skin layers and subcutaneous tissue in lymphedematous limb were studied in vivo using magnetic resonance imaging. High resolution images were obtained with a depth resolution of about 70 microm, using a specific surface gradient coil specially designed for skin imaging and connected to a standard whole-body imager at 1.5 T. Twenty-one patients with unilateral lower extremity lymphedema (11 primary and 10 secondary) were examined. Skin thickness, relaxation times, and relative proton density were calculated in lymphedematous limbs and in contralateral extremities. In diseased limbs, the average skin thickness (2.17 mm) was significantly larger (p = 1.5 x 10(-4)) than that of contralateral limb (1.14 mm). Major cutaneous alterations due to lymphedema took place in dermis. In lymphedematous dermis, the significant increase of relaxation time values could be due to a shift in the equilibrium of water inside this tissue in relation to the interactions between macromolecules and water molecules. In lymphedematous epidermis our results showed an increase in the number of free water protons. Information about water and fat distribution in lymphedema was also obtained using chemical shift weighted images. Our results demonstrated a water retention diffusely spread over the entire dermis, and an important fluid retention located in the interlobular spacing and beside the superficial fascia. Inside the subcutis, the mean thickness of the superficial fat lobules was increased more than that of the deep fat lobules. From all the various measurements we could not distinguish primary from secondary lymphedema.

Transaxial computer tomography of lower extremity lymphedema.

We examined retrospectively 11 patients with isolated unilateral lower limb lymphedema (clinical criteria confirmed by isotope lymphography) using computer tomography. In conjunction with earlier observations, the findings of soft tissue stranding, skin thickening, fat deposition in the epifascial compartment and perimuscular fascial thickening and edema relate to lymph stasis. This noninvasive and relatively simple imaging technique allows analysis of soft tissue changes in leg lymphedema and can be used to evaluate lymphatic insufficiency and its extent as well as document the response to treatment.

Treatment of secondary lymphedema of the upper limb with CYCLO 3 FORT.

Fifty seven patients with secondary lymphedema of the upper limb after previous treatment for breast cancer were treated for 3 months with an extract of Ruscus + Hesperidin Methyl Chalcone (CYCLO 3 FORT) or placebo according to a double-blind protocol in the context of a controlled clinical trial. All patients also underwent manual lymphatic drainage twice a week for at least one month. With CYCLO 3 FORT, the reduction in volume of arm edema, the main assessment criteria, was 12.9% after 3 months of treatment as compared with a placebo (p=0.009). Decreased edema tended to be more marked in the forearm compared with the upper arm where excess fat deposition seemed to dominate over excess fluid accumulation. CYCLO 3 FORT was well tolerated with minimal adverse reaction.

[Principles and results of physiotherapeutic therapy in mechanical lymphatic insufficiency of secondary or primary nature]. / Principes et résultats des traitements physiothérapiques dans les insuffisances lymphatiques mécaniques de nature secondaire ou primitive.

The modern treatment of edemas in mechanical lymphatic insufficiency or lymphedema, combines the restarting of the remaining lymphatic system by manual lymphatic drainage, volumetric reduction by wrapping with bandages and exercise and maintaining the result by wearing a retention device. Intensive courses are necessary, followed by intercurrent course & sometimes a maintenance treatment. In view of the anatomico-functional deficit, all available armamentarium should be used in addition to the measures previously mentioned: hygiene measures, prescription of coumarin (Lysedem). Psychological care is of importance to motivate patients for long-term treatments, if good quality results are to be obtained. However, primary lymphedema seems to respond less favorably than secondary lymphedema.

[Contribution of methods of exploration for the diagnosis and physiopathological interpretation of lymphatic insufficiency of whatever origin]. / Apport des méthodes d'exploration pour le diagnostic et l'interprétation physiopathologique des insuffisances lymphatiques quelle qu'en soit la cause.

The diagnosis of lymphatic deficiency, essentially in clinic, sometimes necessitates complementary investigations to find out exactly the causes or type of the deficiency. All investigations of lymphatic function rely on the injection at a specific point of a substance which will follow the lymphatic ducts. Besides the injection of patent blue, with incomplete information, the value of direct lymphography in investigating a tumorous cause, and of indirect lymphography with less anatomical precision but allowing a kinetic study, should be emphasized. Oedema, always a sign of lymphatic involvement, can be investigated indirectly on the venous side by the usual known methods. Volumetric investigations ought perhaps to take into account the joint role of the vein and the lymph duct in the return to normal after venous occlusion. None of the known methods is absolutely perfect, but isotopic lymphography is, in our opinion, the most plausible correct method, still far from ideal but which can greatly help with the investigation of patients in emergency cases.

[Effects of prolonged physical training on cardiac physiology and morphology in the growing rat using various lipid treatments]. / Effets d'un entraînement physique prolongé sur la physiologie et la morphologie cardiaques du rat en croissance soumis à différents régimes lipidiques.

Weanling male Wistar rats which had been fed for 12 weeks purified diets containing 15% by weight of sunflower oil (SF), high erucic acid rapeseed oil (HEAR) or low erucic acid rapeseed oil (LEAR) and subjected to a treadmill program were compared with sedentary animals fed the same diets, on the basis of cardiac morphology and performances. The rats were trained 5 days a week for 12 weeks, and the speed and duration of the run were progressively increased over 6 weeks until the animals ran continuously for 50 min at 22 m/min with a 4% incline. The following main results were obtained: 1. Food consumption and growth rate decreased in trained animals (Table II). Resting heart rates were not slowed down by training, but were higher in rats fed SF or HEAR than in animals fed LEAR (Fig. 1). Trained animals showed an increasing fatigue during exercise, particularly those fed LEAR (Fig. 2). 2. The ratios of heart weight, muscle weight, kidney weight to body weight, were higher in trained animals, but absolute organ weights were similar in control and trained rats. 3. HEAR caused the highest incidence and number of heart lesions both in sedentary and in trained rats, but in the latter there was a highly significant increase in the number of lesions (Table III). 4. Physical training had different effects on cardiac performances according to the nature of the dietary oil. Thus, the rate of left ventricular pressure rise (dP/dt) decreased only in rats fed, SF or HEAR (Table IV).

Influence of physical training on the effects of dietary oils on cardiac morphology and phospholipids in rats.

Male wistar rats fed purified diets containing 15% sunflower oil (SF) by weight, high erucic acid rapeseed oil (HEAR) or low erucic acid rapeseed oil (LEAR) for 12 weeks and subjected to a moderate treadmill running program were compared with sedentary animals fed the same diets on the basis of cardiac morphology and complete analysis of cardiac phospholipids. HEAR caused the highest incidence and number of heart lesions both in untrained and trained rats but in the latter there was a highly significant increase of the lesions. LEAR gave a higher incidence of lesions than SF in untrained rats but not in trained ones. If compared to SF, HEAR and LEAR increased cardiac diphosphatidylglycerol (DPG) and sphingomyelin (SM) content (mg/g wet tissue) and decreased phosphatidylcholines (PC) and phosphatidylethanolamines (PE) in untrained rats. Marked changes in the fatty acid pattern of these phospholipids were also observed. PE and PC in trained and untrained rats fed HEAR or LEAR contained elevated levels of C 22:5 (n-3) and C 22:6 (n-3) fatty acids whereas the C 22:4 (n-6) and C 22:6 (n-6) polyenes disappeared. Monoenes (C 18:1, C 20:1 or C 22:1) largely incorporated in DPG of rats fed the cruciferous oils. In SM levels of saturated fatty acids (C 16:0, C 18:0, C 20:0) and of n-9 monoenes (C 18:1, C 20:1, C 22:1, C 24:1) were higher in rats fed HEAR or LEAR than in those feds SF. These changes were mainly related to the high level of n-9 monoenes (oleic, eicosenoic and erucic acids) as well as to the high ratio linolenic/linoleic acid present in cruciferous oils. Physical training interacted with the effects of these dietary oils on the cardiac phospholipid composition. The relation between changes in phospholipid composition and the incidence and the number of cardiac lesions is discussed.

[Lymphoedema of the upper limb following surgery or radiotherapy. Investigation by indirect radioactive lymphography (author's transl)]. / Lymphoedème post-chirurgical et radiothérapique des membres supérieurs. Exploration par la lymphographie isotopique indirecte.

Indirect radioactive isotope lymphography using intravenous 99 m Tc-labelled colloidal antimony sulfide was performed on 76 patients with lymphoedema of the upper limb consecutive to surgery or radiotherapy. The time required to reach 50% of maximum radioactivity was taken as index of the lymphatic flow rate, and the patients were divided into 3 groups depending upon the index (< 20 min; 20-60 min; > 60 min). It appears that in huge lymphoedemas the lymphatic flow rate index may remain subnormal, owing to associated veno-occlusive oedema. This non-invasive method provides data on the site and, frequently, on the nature and importance of lymph blockade. It might also help to predict the efficacy of a new drug currently under study.

[The use of arteriography in the pharmacological study of a vasodilator substance]. / Artériographie et densitométrie. Intérêt pharmacologique pour l'étude d'une substance vasodilatatrice

The administration of a vasodilator substance is followed by the development of a higher contrast gradient in a given film in comparison with a reference X-ray carried out in the same subject under comparable technical conditions. Comparative densitometric measurement of the contrast gradient in the two successive arteriographic series, one with and one without the injection, arterial or venous, of a vasodilator substance (Couramine-Rutine) represents a valuable method for the study in man of the action of the substance in a visceral territory. The present study was limited to the kedney (79 cases), ans the territory of the superior mesenteric (46 cases). The absence of any densitometric difference between the two renal series at too low doses of vasodilator substance leads to the supposition of the possibility of a threshold dose of pharmacological activity.