Far-infrared ray for treating chronic lower extremity lymphedema with dermatolymphangioadenitis: a postoperative complication of gynecological tumor resection.

PURPOSE: Lower extremity lymphedema is regarded as a relatively common postoperative complication and is often accompanied with dermatolymphangioadenitis (DLA). This study combines clinical assessment and laboratory investigation to explore therapeutic effects of far-infrared radiation (FIR) therapy for chronic lower extremity lymphedema accompanied with DLA, occurring after gynecological tumor resection. METHODS: Patients who met inclusion and exclusion criteria would be enrolled. They received regular sessions using the FIR therapy machine over the 4-week treatment course. Clinical and laboratory outcome measures were carried out before and after treatment. Clinical outcome measures included DLA seizure frequency (episodes/year), patients' subjective feedback for lymphedema-related symptoms and quality of life (QOL). Laboratory outcome measures included bacterial cultures and concentrations of inflammatory cytokines: IL-1ß, IL-2, IL-4, IL-10, IL-12, IL-18, TNF-α, TNF-ß, caspase-1 and INF-γ, detected in serum and local lymphedema tissue fluid samples using protein microarray and ELISA. RESULTS: Between 2012 and 2016, a total of 120 female patients were screened for study enrollment. Sixty-four recruited patients underwent clinical evaluation both before FIR radiation therapy and 1 year after a single course of FIR radiation therapy. Eleven patients (17.2%), randomly chosen from the study group, underwent additional laboratory analysis of blood and local lymphedema tissue fluid samples. The frequency of DLA decreased following treatment (p < 0.001). Fifty patients (78%) did not experience a single episode of DLA recurrence in the year subsequent to treatment. The efficiency rate calculated using DLA frequencies was greater than 50% for 63 (98%) patients following treatment. Patients reported a subjective decrease in lymphedema-related symptoms (p < 0.05). Patients' QOL scores were higher after treatment (p < 0.001). Laboratory analysis showed an elevation in serum concentration of IL-1ß after FIR therapy (p < 0.05) and reduced local tissue fluid concentrations of inflammatory cytokines IL-2, IL-10 and IL-18 (p < 0.05). Bacterial culture results before and after treatment were both negative. CONCLUSION: FIR radiation therapy provides an effective treatment modality for patients with chronic lymphedema accompanied with DLA that develops secondarily to treatment of gynecological malignancies, whose therapeutic effects may be due to reduced immune dysfunction within local lymphedema tissues.

Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis.

Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

Abnormal mural cell recruitment in lymphatic capillaries: a common pathological feature in chronic lymphedematous skin?

OBJECTIVES: This study aimed to explore the structural and functional characteristics of dermal lymphatic capillaries in patients with chronic LE, specifically focused on the mural cells that are associated with skin lymphatics. METHODS: Forty-four patients (30 primary LE and 14 secondary LE) and eight healthy controls were enrolled in this study. Genetic analysis of the FOXC2 was performed in 18 patients with primary LE. Full-thickness skin was excised and immunohistologically stained for podoplanin and α-SMA. The proportions of α-SMA+ Lv (α-SMA+ Lv%) were calculated. Lymphatic vascular function was assessed by indocyanine green lymphography. RESULTS: Analysis of FOXC2 revealed two mutations in two patients with LDs. Histologically, thirty-nine patients exhibited increased α-SMA+ mural cell coverage of lymphatic capillaries. The α-SMA+ Lv% values in the superficial and deep dermis in patients with primary and secondary LE were significantly higher than in the control group. Compared with imaging findings in healthy limbs, in which the collecting lymphatics were clearly visualized, lymphedematous extremities all exhibited dermal backflow. CONCLUSIONS: Abnormal recruitment of mural cells in dermal lymphatic capillaries is a common pathological event in chronic LE, and may play a role in disease evolution.

Vascularized lymph node flaps can survive on venous blood without an arterial inflow: an experimental model describing the dynamics of venous flow using indocyanine green angiography (With video).

Background: Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods: Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results: All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions: This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

Angiopoietin-2 promotes inflammatory lymphangiogenesis and its effect can be blocked by the specific inhibitor L1-10.

Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF-α expression also increased, with peak TNF-α expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-α stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-α significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection.

Far Infrared Radiation Therapy for Gynecological Cancer-Related Lymphedema Is an Effective and Oncologically Safe Treatment: A Randomized-Controlled Trial.

Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference (p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.

Lymphatic malformation is a common component of Klippel-Trenaunay syndrome.

OBJECTIVES: Few previous studies have focused on the involvement of the lymphatic system in Klippel-Trenaunay syndrome (KTS), although some evidence suggests that lymphatic abnormalities are associated with the disease. The aim of the present study was to investigate the involvement of the lymphatic system in KTS. METHODS: Magnetic resonance lymphangiography (MRL) with the use of gadobenate dimeglumine as the contrast was performed on 32 patients with KTS involving the extremities to evaluate lymphatic vessels, lymph nodes, and veins. RESULTS: Thirty-one of 32 patients exhibited lymphatic vessel and/or lymph node anomalies, including hyperplasia (11/31), hypoplasia or aplasia (20/31) of lymphatic vessels, and lymphedema (31/31) of the affected limbs. Twenty-two patients showed asymmetry of the inguinal nodes exhibiting either the absence, or an increase or a decrease in number and size of the inguinal nodes. Venous dysplasia was found in 31 patients in superficial and/or deep veins. The results showed a high concomitance of malformations of the lymphatic system and veins in the affected limbs of patients with KTS. CONCLUSIONS: Lymphatic system abnormalities as examined with MRL are commonly associated with KTS and are likely to play a significant role in the disorder.

Anatomic and functional evaluation of the lymphatics and lymph nodes in diagnosis of lymphatic circulation disorders with contrast magnetic resonance lymphangiography.

OBJECTIVES: Owing to its structural and anatomic characteristics, imaging of the lymphatic system has been difficult. The conventional diagnostic method of radionuclide-based imaging has the disadvantage of poor resolution. Recent work has shown that magnetic resonance imaging (MRI) can depict lymphatic channels in patients with lymphedema. This study evaluated the anatomic and functional images of contrast MR lymphangiography in the diagnosis of limb lymphatic circulation disorders. METHODS: The study enrolled 27 patients with primary lymphedema. Four patients had bilateral disease, and 23 had unilateral disease. Contrast-enhanced lymphangiography was performed with a 3.0-T MR unit after the intracutaneous injection of gadobenate dimeglumine into the interdigital webs of the dorsal foot. The kinetics of enhanced lymph flow within the lymphatic system were calculated using the formula [speed in cm = total length of visualized lymph vessel in cm/inspection time in minutes] and by comparing dynamic nodal enhancement and time-signal intensity curves between edematous and contralateral limbs. Morphologic abnormalities of the lymphatic system were also evaluated. RESULTS: Examination of the MRIs after injection of the contrast agent showed enhanced lymphatic channels consistently visualized in all clinical lymphedematous limbs and in five contralateral limbs of unilateral lymphedema patients. The speed of flow within the lymphatics of lymphedematous limbs was 0.3 to 1.48 cm/min. Contrast enhancement in inguinal nodes of edematous limbs was significantly less than that of contralateral limbs (P < .01). Dynamic measurement of contrast enhancement showed a remarkable lowering of peak time (P < .01) and peak enhancement (P < .01), and a delay in outflow in inguinal nodes of affected limbs compared with that of control limbs. Postcontrast MRI also depicted varied distribution patterns of lymphatics and abnormal lymph flow pathways within lymph nodes in the limbs with lymphatic circulation disorders. CONCLUSION: Contrast MR lymphangiography with gadobenate dimeglumine is capable of visualizing the precise anatomy of lymphatic vessels and lymph nodes in lymphedematous limbs. It also provides information concerning the functional status of lymph flow transport in the lymphatic vessels and lymph nodes of these limbs.

Far-Infrared Radiation Thermotherapy Improves Tissue Fibrosis in Chronic Extremity Lymphedema.

BACKGROUND: Fibrosis can enhance the exacerbation of lymphedema, which becomes obvious in late stage II-III lymphedema. However, whether far-infrared radiation thermotherapy (FIRT) can cure lymphedema fibrosis is still lack of research. This research was to investigate the therapeutic effect of FIRT on tissue fibrosis in the treatment of Late stage II-III lymphedema. METHODS: Patients accepted only FIRT for a total of 20 sessions. The treatment session duration was 2 hours, and a stable machine temperature of 42°C was maintained throughout treatments. Clinical evaluation and laboratory evaluation were conducted before and after FIRT. Clinical outcome measures included circumference of affected extremity, skin elasticity, ultrasound, patients' subjective assessment, and quality of life (QOL). Laboratory outcome measures included serum and local lymphedema tissue fluid concentrations of fibrosis associated cytokines, tissue growth factor beta-1 (TGF-ß1), interleukin (IL)-1ß, IL-4, IL-18, and caspase-1. RESULTS: Between 2015 and 2016, clinical evaluation of 64 patients with late stage II-III lymphedema was conducted. From this group, 12 cases (18.75%) underwent simultaneous laboratory evaluation. Circumferences of affected extremities improved significantly following treatment (p < 0.001). Skin elasticity of the affected extremity improved significantly (p < 0.05). Ultrasound investigation showed reduced fiber and dense material in the affected tissue (increased gray level 6.322% ± 7.624%, p < 0.001). Patients reported a subjective improvement of their symptoms such as decreased tightness, heaviness, solidity, pain, discomfort, and numbness (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.032, respectively) and improved QOL (p < 0.001). Laboratory results revealed a significant decrease in local tissue fluid concentrations of TGF-ß1 (p = 0.041) and IL-18 (p = 0.049) after course completion. CONCLUSION: FIRT provides an effective treatment for lymphedema tissue fibrosis; it reduces the concentration of fibrosis cytokines in local lymphedema tissues. Consequently, this treatment can reduce the density of fibrosed tissue in the affected extremity, increase skin elasticity, significantly improve clinical symptoms, and improve QOL of patients.

Blockade of angiopoietin-2/Tie2 signaling pathway specifically promotes inflammation-induced angiogenesis in mouse cornea.

AIM: To investigate angiopoietin-2 (Ang-2)/Tie2 signaling pathway involving in inflammatory angiogenesis. METHODS: Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice (6wk old) to induce inflammatory neovascularization. Expression of Ang-2 and Tie2 protein on neovascularization were examined by immunofluorescence. The dynamic expression of Ang-2 mRNA on neovascularization was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Finally, the mouse model of suture-induced corneal neovascularization was used to assess the role of Ang-2/Tie2 signaling pathway in inflammatory angiogenesis by systemic application of L1-10, an Ang-2 specific inhibitor. Mouse corneal hemangiogenesis were evaluated by whole mount immunofluorescence. RESULTS: Both Ang-2 and Tie2 were expressed on newly generated blood vessels in inflammatory cornea. Ang-2 expression was gradually upregulated around 2wk following injury, which was concurrent with an increased number of blood vessels. Blockade of Ang-2/Tie2 signaling pathway obviously promoted angiogenesis in inflammatory cornea. CONCLUSION: Ang-2/Tie2 signaling pathway seems to play an important role during angiogenesis in inflammatory cornea. This may open new therapeutic applications in pathological processes such as corneal graft survival, wound healing and carcinogenesis.

Far infrared ray (FIR) therapy: An effective and oncological safe treatment modality for breast cancer related lymphedema.

BACKGROUND: The incidence of breast cancer related lymphedema is approximately 5%. Far infrared ray (FIR) treatment can potentially reduce fluid volume and extremity circumference as well as the frequency of dermato-lymphangitis (DLA). However, there is no published data on the oncological safety of FIR and the potential for activation of any residual breast cancer cells. The aim of this study is to investigate the safety of far infrared ray (FIR) treatment of postmastectomy lymphedema, clinically and in vitro. METHODS: Patients who underwent mastectomy more than 5years ago complicated by upper extremity lymphedema for more than 1year were included. The enrolled patients were divided into an FIR treatment group and a control group (conservative treatment using bandage compression). Outcome measures included tumor markers (CA153, CA125), ultrasonography of relevant structures and monitoring for adverse reactions 1year after treatment. For the in vitro part of the study, the effects of FIR on human breast adenocarcinoma cell lines (MCF7, MDA-MB231) compared to the effects of FIR on human dermal fibroblasts as a control were considered. The viability, proliferation, cell cycle and apoptotic statistics of the adenocarcinoma and human dermal fibroblast cell lines were analyzed and compared. RESULTS: Results demonstrated that after treatment with FIR, tumor marker (CA153, CA125) concentrations in both the FIR and control groups were not elevated. There was no statistically significant difference between FIR and control group marker expression (p>0.05). Furthermore, no patients were diagnosed with lymphadenectasis or newly enlarged lymph nodes in these two groups. Importantly, there were no adverse events in either group. The in vitro experiment indicated that FIR radiation does not affect viability, proliferation, cell cycle and apoptosis of fibroblasts, MCF-7 and MDA-MB-231 cells. CONCLUSIONS: FIR should be considered as feasible and safe for the treatment of breast cancer related lymphedema patients 5years after mastectomy. FIR does not promote recurrence or metastasis of breast cancer and is a well-tolerated therapy with no adverse reactions.

Pathological Changes of Lymphedematous Skin: Increased Mast Cells, Related Proteases, and Activated Transforming Growth Factor-ß1.

BACKGROUND: Skin fibrosis is a clinically serious pathological process of secondary lymphedema (SLE). Previous studies have shown that mast cells (MCs) are involved in lymphedema (LE) and play a key role in the pathological process of skin fibrosis. However, the role of the protease chymase and transforming growth factor-ß1 (TGF-ß1) secreted by MCs in the fibrotic skins of patients with secondary lower limb LE has not been explored. METHODS AND RESULTS: In this study, full-thickness skin biopsies of lymphedematous limbs from seven SLE patients and control samples from seven healthy controls were harvested. The skin samples were assayed by Masson, immunohistochemical, and immunofluorescence staining and were analyzed by western blot and enzyme-linked immunosorbent assay. The number of MCs and the expression of proteases, TGF-ß1, and latency-associated peptide TGF-ß1 (LAP TGF-ß1) were analyzed. The number of MCs and the expression of chymase, TGF-ß1, and LAP TGF-ß1 were increased in fibrotic skin compared with normal skin. The increased expression of TGF-ß1 on lymphatic vessels, endothelial cells, and in skin interstitial tissues overlapped with chymase expression. CONCLUSIONS: Our results demonstrate that chymase and TGF-ß1 expression was significantly increased in the fibrotic skin of secondary lower limb LE. The increased expression of chymase in the skin may play an important role in the development fibrosis in the lymphedematous skin. We speculate that chymase may facilitate the release of LAP TGF-ß1 to generate activated TGF-ß1, and the upregulation of active TGF-ß1 can promote fibrosis in the SLE skin.

[Expression of hyaluronic acid and its receptor in the process of wound healing in different skin tissues and its significance].

OBJECTIVE: To explore the expression of hyaluronic acid (HA) and its receptor, Cluster of differentiation 44 (CD44) in proliferative scar and in the process of wound healing of normal human adult skin and fetal skin, and the effect of HA and its receptor on the process of human fetal skin scarless healing. METHODS: An incision and then a hypodermic cavity were made on each side of the dorsal median line of 32 female adult BALB/c rats. Skin grafts from 8 human fetuses delivered by natural abortion, full-thickness skin grafts from 8 normal adults undergoing plastic operation, skin wound sample from the donor sites in legs of 8 patients undergoing dermatoplasty with intermediate split thickness skin graft, and proliferative scar from 8 patients of plastic surgery, non-adult and adult, were grafted into the hypodermic cavities. The levels of HA and its receptor were examined by radioimmunoassay, immunohistochemistry and flow cytometry. RESULTS: The level of HA in normal fetal skin was 143 micro g/g +/- 10 micro g/g, 283 micro g/g +/- 12 micro g/g 12 hours after injury, 315 micro g/g +/- 12 micro g/g one days after injury, reached the peak (321 micro g/g +/- 12 micro g/g) 3 days after injury, and then decrease, became 319 micro g/g +/- 11 micro g/g one week after injury (P > 0.05 in comparison with that 3 days after injury). The level of HA in normal fetal skin was 143 micro g/g +/- 10 micro g/g, significantly higher than that in normal adult skin (51 micro g/g +/- 4 micro g/g), skin wound of normal adult (92 micro g/g +/- 6 micro g/g), and proliferative scar (72 micro g/g +/- 5 micro g/g, all P < 0.01). The level of HA in wounded adult skin was significantly higher than that in the proliferative scar, and even much higher than that in normal skin (P < 0.01). The level of CD44 in normal fetal skin was significantly higher than that in proliferative scar and adult skin (all P < 0.01). The level of CD44 in wounded fetal skin 24 hours after injury decreased, significantly lower than that in normal fetal skin. There was no statistically significant difference between the level of CD44 in fetal skin one week after injury and that 24 hours after injury (P > 0.05). The level of CD44 in wounded adult skin was significantly higher than that in the normal adult skin (P < 0.01). The level of CD44 in the proliferative scar was between the level of CD44 in normal adult skin and that in wounded adult one. In normal fetal skin, CD44, positively stained at a moderate level, was distributed in keratinized cells, basic cells of hair follicle, and fibroblast of dermis. After injury, staining of CD44 became milder, especially by the incision. Immunohistochemistry showed that in normal adult skin, CD44 was distributed mainly in fibroblast of dermis and basic cells of hair follicle, weakly positively stained. After injury, the staning became stronger. CONCLUSION: The expression of HA and its receptor during the process of wound healing in human fetal skin is different from that in proliferative scars and adult skin, which might be one of the important causes of scarless healing of wounded fatal skin.

Functional lymphatic collectors in breast cancer-related lymphedema arm.

BACKGROUND: The pathophysiology of breast cancer-related lymphedema (BCRL) is poorly understood. The present study evaluated the lymphatic collectors in the arms of patients with BCRL. METHODS AND RESULTS: In total, 123 patients with ipsilateral BCRL who had undergone magnetic resonance lymphangiography using gadobenate dimeglumine as a contrast agent were enrolled in this study. Morphological changes and the numbers of collecting lymphatic vessels were recorded. Associations between the number of visualized lymphatic collectors and edema accumulation, subcutis thickness, and the BCRL duration and latency were analyzed. Tortuous and significantly dilated lymphatic collectors were visualized in the lymphedematous arms of 104 patients (85%). The median number of visualized lymphatic collectors was four. The duration of BCRL was weakly but significantly correlated with the number of lymphatic collectors (rs=0.2054, p=0.0226). The differences in the tissue water content and thickness of the subcutis between the bilateral arms demonstrated moderate correlations with the number of collecting lymphatics (rs=0.31 and 0.35, respectively; p<0.01). More lymphatic collectors tended to be seen in more advanced cases. There was no statistical difference in the amount of lymphatic vessels among different breast cancer treatment methods. CONCLUSIONS: The number of functional remaining lymphatic collectors increases with the prolongation and severity of BCRL. This may imply persistent reactions of lymphatic collectors in response to lymphostasis.

[Comparison study of radionuclide lymphoscintigraphy and dynamic magnetic resonance lymphangiography for the diagnosis of extremity lymphedema].

OBJECTIVE: To compare the role of radionuclide lymphoscintigraphy and dynamic magnetic resonance lymphangiography (MRL) for the diagnosis of extremity lymphedema. METHODS: Sixteen patients with primary extremity lymphedema and two with Klippel-Trenaunay syndrome combined with lymphedema were examined by lymphoscintigraphy using the tracer 99Tc-labelled dextran, and also by MRL using gadobenate dimeglumine as contrast agent. The results of morphological abnormalities and functional state of the lymphatic system at affected limbs from the two imaging methods were compared. RESULTS: Lymphatic vessels were imaged in 14 of 18 limbs with lymphedema using MRL, compared with one of 18 using lymphoscintigraphy. MRL detected the inguinal nodes in 16 of 17 patients, whereas lymphoscintigraphy revealed inguinal nodes in only nine cases. MRL revealed more precise information about structural and functional abnormalities of lymph vessels and nodes than lymphoscintigraphy by real-time measurement of lymph flow in vessels and nodes. CONCLUSIONS: Dynamic MRL is more sensitive and accurate than lymphoscintigraphy in the detection of anatomical and functional abnormalities in the lymphatic system in patients with extremity lymphedema.

[Treatment of chronic extremity lymphedema with manual lymph drainage].

OBJECTIVE: To evaluate the effect of manual lymph drainage on chronic extremity lymphedema. METHODS: Fifty patients with chronic lymphedema of extremity were treated with manual lymph drainage (MLD) complex decongestion therapy. Among them, 29 had primary lymphedema, 21 had secondary lymphedema. 42 had lymphedema of lower extremity and 8 had lymphedema of upper limb. The result of treatment was evaluated with measurement of circumference of extremities and edema fluid in tissue with Multiple-frequency bioelectrical impedance analysis. RESULTS: After 1-2 treatment courses, all 50 patients showed significant decrease of circumference of lymphomatous limbs (P < 0.05) and remarkable reduction of accumulated edema fluid in tissue (P < 0. 05). There was highly correlation between the decrease of limb circumference and edema fluid in tissue (r(s) = 0.774, P < 0.01). CONCLUSIONS: MLD complex decongestion therapy is effective for the treatment of chronic lymphedema of extremity.

[Diagnosis of peripheral lymph circulation disorders with contrast MR lymphangiography].

OBJECTIVE: To evaluate anatomical and functional images of contrast MR lymphangiography in the diagnosis of limb lymphatic circulation disorders. METHODS: 30 patients with limb lymphedema were enrolled in the study. There were 27 patients of primary lymphedema and 3 of secondary lymphedema. Contrast enhanced lymphangiography was performed with 3.0 T MR Unit after intracutaneous injection of gadobenate dimeglumine into the interdigital webs of the dorsal foot and hand. The kinetics of enhanced lymph flow within the lymphatics were calculated using the formula: Speed (cm) = total length of visualized lymph vessel (cm)/ inspection time (minutes) and by comparing dynamic nodal enhancement and time-signal intensity curves between edematous and contralateral limbs. Morphological abnormalities of the lymphatic system were also evaluated. RESULTS: Following injection of the contrast agent enhanced lymphatic channels were consistently visualized in all clinical lymphedematous limbs and five contralateral limbs of unilateral lymphedema cases. The speed of enhanced flow within the lymphatics of lymphedematous limbs ranged from 0.30 to 1.48 cm/min. The contrast enhancement in inguinal nodes of edematous limbs was significantly lower than that of contralateral limbs (P < 0.01). Dynamic measurement of contrast enhancement showed a remarkable lowering of peak time (P < 0.01) and peak enhancement (P < 0.01) and a delay in outflow in inguinal nodes of affected limbs compared with that of control limbs. Post-contrast MR imaging also depicted varied distribution patterns of lymphatics and abnormal lymph flow pathways within lymph nodes in the limbs with lymphatic circulation disorders. CONCLUSIONS: Contrast MR lymphangiography with gadobenate dimeglumine was able to visualize the precise anatomy of lymphatic vessels and lymph nodes in lymphedematous limbs. It also provided comprehensive information about the functional status of lymph flow transportation in lymphatics and lymph nodes.

[Experimental studies of VEGF-C gene for the treatment of chronic obstructive lymphedema in mouse tail model].

OBJECTIVE: To study the therapeutic effect of vascular endothelial growth factor C (VEGF-C) gene for chronic obstructive lymphedema in mouse tail model which may provide a new treatment for lymphedema. METHODS: RT-PCR and immunoabsorption were applied to detect VEGF-C gene expression in fibroblasts and secretion of VEGF-C protein in COS7 cells respectively after pCDNA3.1 (+) VEGF-C transfection. A mouse tail model of chronic obstructive lymphedema was created. Then the pcDNA3.1-VEGF-C plasmid was injected into the tail. The effect of modulating lymphangiogenesis was observed. RESULTS: Compared with control group, overexpression of VEGF-C enhanced lymphangiogenesis in vivo and mouse tail skin suffering chronic obstructive lymphedema was improved by VEGF-C gene significantly. CONCLUSIONS: VEGF-C can improve the lymphedema through enhancing lymphangiogenesis.

[Experimental study of gene therapy with human vascular endothelial growth factor-c in lymphedema].

OBJECTIVE: To study the efficacy of gene therapy with human vascular endothelial growth factor-c (VEGF-C) on obstructive lymphedema. METHODS: Two animal models of lymphedema were created: one in the right hind limb of adult New Zealand white rabbits and the other in SD mouse tail. Each model was randomly divided into two groups to receive intradermal injection of either VEGF-C gene (experimental group), or saline(control group). In rabbit model, the volume change of affected limb was measured. In mouse model, biopsy was performed after 3 weeks treatment to detect the expression of VEGF-C mRNA and proteins. The lymphagenesis was evaluated by immunohistochemical examination with lymphatic endothelium hyaluronan receptor antibody. RESULTS: The volume of the affect rabbit limb decreased by (24.40 +/- 1.08) ml in experimental group, compared with (5.80 +/- 1.92) ml in control group (P = 0.0001). The expression of VEGF-C mRNA and protein increased markedly in experiment group, but not in controls. More lymphatic vessels with large caliber were seen in experiment group (P = 0.0004). CONCLUSIONS: VEGF-C gene therapy may alleviate or treat lymphedema by inducing lyphmangiogenesis.