Short time effects of radiotherapy on lymphatic vessels and restorative lymphatic pathways: experimental approaches ina mouse model.

Radiotherapy (RT) is an important component in the therapeutic approach to oncologic conditions. This study presents the investigative results on the impact of RT on lymphatic vessels and on the regenerative response of the lymphatic system in a mouse model. We first irradiated 3 groups of ten mice using brachytherapy in a single treatment of 20 Gy. We then performed morphological examination of the irradiated lymphatic vessels using an in vivo microscopic transillumination technique at 2, 4, and 6 weeks. Next we evaluated lymphatic flow using lymphoscintigraphy and in vivo microscopy at 6 to 11 weeks in: 10 additional mice following irradiation as above (IR), in 10 mice following incision of a lymphatic vessel (I), and in a non-treated control group of 10 mice (N). Intact lymphatic vessels were observed in all mice at 2, 4, and 8 weeks following the single dose of radiotherapy in the first group of mice and normal lymphatic flow was fully restored in the irradiated (IR) and incised (I) mice indicating that the reparative substitution lymphatic pathways are functioning normally. We found that following irradiation with one dose of 20 Gy, lymphatic vessels were not visibly damaged and also that lymphatic flow was consistently restored and substitutive lymphatic pathways formed.

Identification and description of the axillary web syndrome (AWS) by clinical signs, MRI and US imaging.

The Axillary Web Syndrome (AWS) follows surgery for breast neoplasia and consists of one, or more frequently two or three, cords of subcutaneous tissue. Cords originate from the axilla, spread to the antero-medial surface of the arm down to the elbow and then move into the antero-medial aspect of the forearm and sometimes into the root of the thumb. The purpose of this study was to compare two techniques, ultrasound (US) and Magnetic Resonance Imaging (MRI) for their sensitivity and accuracy in identifying AWS cords and to provide insights to the origin of this pathology. US examinations were performed on fifteen patients using a high frequency probe (17 MHz). We first palpated and marked the cord with location aided by maximum abduction. To identify the cord with MRI (1.5 Tesla), a catheter filled with a gel detectable under MRI was placed on the skin at the site of the cord. We found that in some US cases, the dynamic abduction maneuver was essential to facilitate detection of the cord. This dynamic method on ultrasound confirmed the precise location of the cord even if it was located deeper in the hypodermis fascia junction. US and MRI images revealed features of the cords and surrounding tissues. Imaging the cords was difficult with either of the imaging modalities. However, US seemed to be more efficient than MRI and allowed dynamic evaluation. Overall analysis of our study results supports a lymphatic origin of the AWS cord.

Manual Lymphatic Drainage Increases the Number of Opened Lymphatic Pathways in Patients with Lower Limb Lymphedemas: A Sequential Research on 80 Patients.

The purpose of this study was to lymphoscintigraphically assess the effect of skin mobilization, nonspecific massage, and manual lymphatic drainage (MLD) on the root of the lower limb in patients with lower limb lymphedema. Lower limb root lymphoscintigraphical exams of 80 patients with lower limb lymphedema were analyzed. All patients underwent our stand 3 phase protocol and then were subjected to the 4th phase which included 3 subphases. Images were taken directly after the injection (subphase 1), after pinching and stretching the injection site (subphase 2), after nonspecific massage was applied to the injected site (subphase 3) and after manual lymphatic drainage of the injected site (subphase 4). The number of opened lymphatic pathways was analyzed and compared after and between each subphase (SP). SP 1 displayed open lymphatic pathways in 22 of the 80 cases (27.5%). SP 2 displayed newly opened lymphatic pathways in 48 of the 80 cases (60.0%). SP 3 displayed newly opened lymphatic pathways in 57 of the 80 cases (71.3%). Only 9 of these 57 cases did not show improvement following the next SP. SP 4 displayed newly opened lymphatic pathways in 60 of the 80 cases (75.1%). MLD improved the visualization of the lymphatic pathways in 48 cases (60%) compared to phase 3. MLD was the only technique to allow visualization of the lymphatic drainage at the level of the root of the edematous limb in 6 cases (7.5%). Physical therapy leads to a greater number of lymphatic collaterals opening in a region where no other complex decongestive therapy technique can be applied.

Impact of manual lymphatic drainage on hemodynamic parameters in patients with heart failure and lower limb edema.

Manual lymphatic drainage (MLD), intermittent sequential pneumatic therapy (ISPT), multilayered bandages (MLB), and compression garments are main techniques in conservative treatment of peripheral lymphedema. Since 1990, it has been thought that ISPT applied to both lower limbs simultaneously should not be used for patients with heart failure because right atrial, pulmonary arterial, and pulmonary wedge pressures may increase to a critical point. In 2005, these same results were observed in patients with heart failure wearing MLB. For these reasons, MLB and ISPT have been contraindicated during lymphedema treatment in cardiac patients. The aim of this study was to determine if we may continue the treatment of lower limb lymphedema using MLD in patients with heart failure. We evaluated hemodynamic parameters using echography during MLD in patients with cardiac disease and obtained circumferential measurements of the edematous limb before and after treatment. MLD treatment significantly decreased the limbs as expected. The heart rate also decreased following MLD in contrast with all other hemodynamic parameters which were not affected by MLD. The findings suggest that there is no contraindication to use MLD in patients with heart failure and lower limb edema.

Are there hemodynamic implications related to an axillary arch?

The axillary arch (AA) has been thoroughly studied and described as a supernumerary muscle, present unilaterally or bilaterally. This study aims to provide an in vivo demonstration of the influence of an AA on vascular, biometrical, and hemodynamic parameters. Two-hundred thirty-nine subjects with a mean age of 21.3 ± 2.7 years participated in this study. After visual screening by two independent experts, 20 subjects (8.4%) presented with an AA unilaterally (n = 12) or bilaterally (n = 8). An echo-Doppler examination of the vena and arteria axillaris was performed to measure blood flow, velocity of circulating elements, and blood vessel diameter in different positions of the arm (abduction: 45°, 90°, 90° combined with exorotation 'ER', 120°). The arteria axillaris parameters, measured in the test (n = 9; six women, three men) and control group (n = 11; six women, five men), were equivalent for all tested positions. The axillary vein parameters, compared to variations within the groups, revealed no significant differences. However, when comparing variation between groups, significant differences were found for (i) diameter in 90° abduction + ER and 120° abduction; (ii) velocity in 90° and 120° abduction. Blood flow demonstrated no significant difference between groups in any of the positions. The results of this study indicate that there is no functional vascular implication of the AA in the test samples. This study also questions the interpretation of some hypotheses regarding the AA and entrapment syndromes.

Effect of lateralization and handedness on the function of the lymphatic system of the upper limbs.

In the upper limbs (UL), lateralization or handedness coincides with functional (and/or anatomical) asymmetries. Scintigraphic techniques were used to investigate the function of the UL lymphatic system and to determine whether significant differences exist between right and left limbs. With limbs at rest, 99mTc-labeled HSA nanosized colloids were injected intradermally into the forearms in 19 volunteers. Activities in the axillary nodes were recorded 1 minute later, then every 20 minutes up to100 minutes later and reported as per ten thousands of injected activity. When comparing right injections to left injections, no significant difference was found using an unpaired statistical test. However, with paired t-tests, axillary node activity (mean +/- SD) was significantly higher when the right limb was injected than when the left limb was injected, both overall (n = 19) (at 100 minutes: 454 +/- 88 versus 299 +/- 45: p = 0.014) and when the 13 right-handed cases were analyzed separately (501 +/- 116 versus 285 +/- 65: p = 0.004). No difference was found for the six left-handed volunteers. Our results demonstrate, at least in the right handed subjects, the functional asymmetry of the superficial lymphatic system of the right and left upper limbs.

Axillary web syndrome: nature and localization.

Axillary Web Syndrome (AWS) is a complication that can arise in patients following treatment for breast cancer. It is also known variously as syndrome of the axillary cords, syndrome of the axillary adhesion, and cording lymphedema. The exact origin, presentation, course, and treatment of AWS is still largely undefined. Because so little is known about AWS, we undertook a case series study consisting of 15 women who had undergone breast cancer surgery and presented with AWS. All subjects received a clinical examination which included body size determination and detailed measurements of the size and location of the cords. The cords were found to originate from the axilla, continue on the medial aspect of the arm up to the epitrochlea region, then to the anteromedian aspect of the forearm, and finally reaching the base of the thumb. The cords averaged approximately 44% of the limb length. Correlation of the cord location with anatomical studies shows that in fact this path follows the specific course taken by the antero-radial pedicle which arises at the anterior aspect of the elbow from the brachial medial pedicule to anastomose in the axilla at the level of the lateral thoracic chain nodes. Although our series is small, the correspondence between the physical findings and the anatomical studies strongly supports the notion that the cords are lymphatic in origin.

MR imaging, proton MR spectroscopy, ultrasonographic, histologic findings in patients with chronic lymphedema.

Lymphedema is a progressive disease with multiple alterations occurring in the dermis. We undertook this study using high-frequency ultrasonography (US), magnetic resonance imaging, proton MR spectroscopy and histology to examine structural changes occurring in the subcutaneous tissue and precisely describe the nature of intralobular changes in chronic lymphedema. Four cutaneous and subcutaneous tissue biopsies from patients with chronic lymphedema during lymphonodal transplantation were studied. We performed US with a 13.5 MHz transducer, TSE T1 and TSE T2 magnetic resonance images with and without fat-suppression, MR Chemical Shift Imaging Spectroscopy and histological evaluation on these biopsies. We found that normal subcutaneous septa are seen as hyperechogenic lines in US and hyposignal lines in MRI and that hyperechogenic subcutis in US can be due to interlobular and intralobular water accumulation and/or to interlobular and intralobular fibrosis. Our study also confirms the usefulness of MR spectroscopy to assess water or fat content of soft tissue. Thus, multiple imaging modalities may be necessary to precisely delineate the nature of tissue alterations in chronic lymphedema.

Resistance to activated protein C: evaluation of three functional assays.

Resistance to Activated Protein C (APC) was evaluated using 3 different methods: two of them were based on the prolongation of the Activated Partial Thromboplastin Time (APTT) using 2 different APTT reagents in the presence of APC, whereas the third method was based on the prolongation of prothrombin time when APC is added. The three methods were significantly correlated. APTT-based assays were sensitive to factor XII deficiency, whereas thromboplastin-based assay was sensitive to factor VII deficiency (< 0.5 UI/ml), which surestimates the response to APC. In contrast, an increase in factor VIII (F. VIII) level is associated with a decreased response to APC, when APTT-based assays are used, whereas thromboplastin-based assay is unmodified. During pregnancy, a decreased response to APC is observed, which is not only due to the increase in F. VIII, since thromboplastin-based assay is also modified. In Protein S (PS) immuno-depleted plasma, the low response to APC is corrected by addition of free PS: the thromboplastin-based assay was the most sensitive one to PS deficiency. However, in patients with congenital PS deficiency, there was no correlation between APC-resistance and free PS level. In patients with lupus anticoagulant, discrepancies were observed between the 3 methods, but with a high frequency of low response to APC. For the 3 assays, there was a good differentiation and correlation between normal and pathological results, the thromboplastin-based assay being perhaps the most discriminating. However, 3 unrelated thrombophilic patients showed normal results using thromboplastin-based assay, although they were APC-resistant using APTT-based assays. For 2 patients, this discrepancy can be explained by high levels of F. VIII. For the last patient, an abnormal F. VIII, resistant to APC can be suspected.

[Hemodynamic impact of pressotherapy]. / Répercussions hémodynamiques de la pressothérapie.

We study the hemodynamic effects of pressotherapy in 11 patients (mean age : 68 +/- 10 years) with uncomplicated acute myocardial infarction (n = 6) or with chronic ischemic heart failure (n = 5). We measure the right auricular pressure (RAP), the mean pulmonary arterial pressure (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (T 20 min) and 30 minutes after the end of pressotherapy (T 30 min). We use five-chambered leg garments with 80 mm Hg pressure during 20 minutes. The wavelike action (from the bottom to the top) is intermittent: the compression time is 10 second (sec); compression is maintained during 60 sec; deflation time is 15 sec. After 20 minutes pressotherapy (t 20) the 3 variables increase: RAP: from 3.6 +/- 5 to 7 +/- 7 mm Hg (P less than 0.001), MPAP: from 25 +/- 14 to 29 +/- 17 mm Hg (p less than 0.01) and the PWP from 10 +/- 8 to 17 +/- 11 Hg (p less than 0.01). This rise is particularly important in heart failure patients: from 18 +/- 8 to 29 +/- 8 mm Hg for the PWP, with cough in one patient. At T 30 these 3 variables decrease and return nearly to initial values: respectively 2.7 +/- 4.7 (RAP), 24 +/- 14 (MPAP), 12 +/- 8 mm Hg (PWP). In conclusion pressotherapy increases RAP and pulmonary pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Rehabilitation protocol in upper limb lymphedema.

Edema of the upper limb is, frequently, very invalidating. The physical treatment for edema of the upper limb consists on a combination of different therapies: manual lymphatic drainage (MLD), intermittent sequential pressotherapy (IPP) with a very low intensity, multilayer bandages (MLB), and compression sleeves. Patients are not hospitalized. In the first step of physical treatment, the patients are treated daily during 2 or 3 weeks with different therapies (MLD, IPP and MLB). During the second step, bandages are no more used. The compression garments are applied after this 2 or 3 weeks period. The physical treatment consist now in: manual lynphatic drainage and intermittent sequential pressotherapy (with low intensity). The frequency of the physical treatment is progressively decreased.

[Lower limb edema and steatorrhea: value of scintigraphic technics]. / Oedème d'un membre inférieur et stéatorrhée: apports des techniques isotopiques.

The authors report the case of a young woman with right lower limb edema who also presented one steatorrhea. Her clinical history is typical for one primary lymphedema and the lymphoscintigraphic investigation of the lower limbs confirms the diagnosis. The scan showed the absence of the right iliac and lomboaortic lymph nodes but also that the thoracic duct was normally present. One C14-triolein breath test is pathological and proves the malabsorption of the fats. The authors discuss the interest of the scintigraphic techniques in such case and review the problem of the association between lower limb lymphedemas and fatty malabsorption.

[Limb edema and lymphoscintigraphy]. / Oedèmes des membres et lymphoscintigraphies.

Lymphoscintigraphic investigations represent techniques of nuclear medicine very contributive for the management and treatment of the limb edemas, either primary or secundary. Their principle is presented and methodologies proposed in the literature are reviewed. Their diagnostic contributions are detailed. The sensitivities and specificities of several protocols of investigation are reported. Some limitations of these examinations are analyzed and discussed. Clinical indications for their use are proposed and their interest with regard to the various treatments that can be applied to these limb edemas is discussed.

[The effects of pressotherapy on cardiovascular hemodynamics]. / Influence de la pressotherapie sur l'hémodynamique cardio-vasculaire.

Right auricular and pulmonary pressures increase during pressotherapy particularly in heart failure patients.

Imaging techniques in the management and prevention of posttherapeutic upper limb edemas.

BACKGROUND: Upper limb edema remains the most frequent complication after treatments for breast carcinoma. Various imaging techniques can be used to prevent these complications, to manage them, and to diagnose the possible lymphonodal evolution that may underlie these events. In the present paper, these techniques are reviewed. METHODS: Based on clinical experience as well as on the data from the literature, these imaging techniques are presented, and their contributions are analyzed. RESULTS: The pre- and post-operative imaging and research techniques of the so-called sentinel nodes (using blue dye, and/or lymphoscintigraphy, and/or gamma probe) appear to be very promising for defining patients in whom axillary node clearance either might be avoided or is indicated. Lymphoscintigraphic investigations also can be used after surgery and/or radiation therapy to define patients who either are at risk to develop upper limb edema or present with latent edema. In patients with clinically obvious edema, even if it is limited, lymphoscintigraphic techniques can provide a morphologic and functional definition of the condition. Venous echo Doppler can be used when abnormalities of the venous return are suspected. In diagnosing the lymphonodal evolution of the disease, techniques like immunoscintigraphy, positron emission tomography (using 18-fluoro-2-deoxy-D-glucose), X-ray computed tomography, and nuclear magnetic resonance imaging can contribute. CONCLUSIONS: Various imaging techniques can be used to prevent and/or to manage the upper limb edema that may complicate the treatment(s) of the patients with breast carcinoma.

The physical treatment of upper limb edema.

BACKGROUND: Edema of the upper limb, without any doubt, constitutes the most invalidating complication of breast carcinoma treatment. The swelling of the limb results from decreased liquid evacuation by surgical intervention at the axillary level and also by the eventual treatment by cobaltotherapy. METHOD: The physical treatment for edema of the limb consists of a combination of therapies that were tested for their effectiveness in laboratories on healthy students and also on patients who underwent surgery for breast carcinoma. The treatment consists of the application of manual lymphatic drainage (type Leduc), the use of multilayered bandages, and the use of intermittent pneumatic compression. The population studied was represented by 220 patients who underwent breast surgery. The authors followed their evolution during the first 2 weeks of treatment. Patients were not hospitalized. The edema was measured by using marks tattooed on the skin. RESULTS: The limb that developed edema was compared with the healthy limb. The most important reduction was obtained in the first week. The decrease was equivalent to 50% of the average of the difference between both upper limbs. During the second week, the results obtained stabilized; however, there was a slight decrease at the end of the second week. CONCLUSIONS: The physical treatment of edema represents the preferred therapeutic approach. However, it must answer to well-defined criteria to be efficient and for long-lasting effects. The physical treatment is used to treat outpatients, allowing them to follow a normal lifestyle.