Lymphscintigraphic evaluation of manual lymphatic drainage for lower extremity lymphedema.

March 2006

Kafejian-Haddad AP, Perez JM, Castiglioni ML, Miranda Junior F, de Figueiredo LF.

Vascular Surgery Department, "ABC" Medical School, Sao Paulo, Brazil. apkh@uol.com.br

To evaluate the effect of manual lymphatic drainage on technetium-99m-labeled dextran (99mTcDx) transport, 16 patients with lymphedema of lower extremities underwent two lymphscintigraphy exams by injecting 99mTcDx intradermally into the first interdigital space of the affected extremity. The first was a control examination at rest followed by an examination which included a manual lymphatic drainage session after the injection of the 99mTcDx. Images were obtained 45 minutes and three hours after the injection of the radioisotope.

Extremity volumes were also measured before and after the drainage session. The findings from the examinations were assessed in a quantitative, semiquantitative and qualitative manner and compared without and with drainage. The analyses of the extremities' circumference before and after the drainage by paired t-test revealed a significant decrease. The analyses of the quantitative, semi-quantitative and qualitative evaluations evidenced no significant difference, without or with drainage, within the 45-minute and three-hour periods.

Thus, manual lymphatic drainage caused an effective reduction in the circumference of the extremities but did not have a significant effect in the transport of 99mTcDx.PMID: 16724509 [PubMed - in process]

From Lymphology

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Early lymph vessel development from embryonic stem cells

Researching the Cure for Lymphedema

May 2006

Early lymph vessel development from embryonic stem cells.

Kreuger J, Nilsson I, Kerjaschki D, Petrova T, Alitalo K, Claesson-Welsh L. Department of Genetics and Pathology, Uppsala University, Sweden. johan.kreu...@genpat.uu.se

OBJECTIVE:

The purpose of this study was to establish a model system for lymph vessel development based on directed differentiation of murine embryonic stem cells.

METHODS AND RESULTS:

Stem cells were aggregated to form embryoid bodies, and subsequently cultured in 3-dimensional collagen matrix for up to 18 days. Treatment with vascular endothelial growth factor (VEGF)-C and VEGF-A individually enhanced formation of lymphatic vessel structures, although combined treatment with VEGF-C and VEGF-A was most potent and gave rise to a network of LYVE-1, podoplanin, Prox1, and VEGF receptor-3 positive lymphatic vessel structures running parallel to and apparently emanating from, capillaries. In contrast, fibroblast growth factor-2, hepatocyte growth factor, or hypoxia had little or no effect on the development of the early lymphatics. Further, cells of hematopoietic origin were shown to express lymphatic markers. In summary, different subpopulations of lymphatic endothelial cells were identified on the basis of differential expression of several lymphatic and blood vessel markers, indicating vascular heterogeneity.

CONCLUSIONS:

We conclude that the present model closely mimics the early steps of lymph vessel development in mouse embryos.

PMID: 16543496 [PubMed - indexed for MEDLINE]

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Differentiation of Lymphatic Endothelial Cells From Embryonic Stem Cells on OP9 Stromal Cells.

Kono T, Kubo H, Shimazu C, Ueda Y, Takahashi M, Yanagi K, Fujita N, Tsuruo T, Wada H, Yama****a JK. Molecular and Cancer Research Unit, HMRO and Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Japan; Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Japan; Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan; and PRESTO, Japan Science and Technology Agency, Japan.

OBJECTIVE:

The discovery of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3) has started to provide an understanding of the molecular mechanisms of lymphangiogenesis. The homeobox gene prox1 has been proven to specify lymphatic endothelial cells (ECs) from blood ECs. We investigated the process of lymphatic EC (LEC) differentiation using embryonic stem (ES) cells.

METHODS AND RESULTS:

VEGFR-2(+) cells derived from ES cells differentiated into LECs at day 3 on OP9 stromal cells defined by the expression of prox1, VEGFR-3, and another lymphatic marker podoplanin. VEGFR-2(+) cells gave rise to LYVE-1(+) embryonic ECs, which were negative for prox1 on day 1 but turned to prox1(+) LECs by day 3. VEGFR-3-Fc or Tie2-Fc, sequestering VEGF-C or angiopoietin1 (Ang1), suppressed colony formation of LECs on OP9 cells. However, addition of VEGF-C and Ang1 in combination with VEGF to the culture of VEGFR-2(+) cells on collagen-coated dishes failed to induce LECs. LEC-inducing activity of OP9 cells was fully reproduced on paraformaldehyde-fixed OP9 cells with the conditioned medium.

CONCLUSIONS: We succeeded in differentiating LECs from ES cells and revealed the requirements of VEGF-C, Ang1, and other unknown factors for LEC differentiation.

PMID: 16690875 [PubMed - as supplied by publisher]

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Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development.

A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells.

Comparative Evaluation of FGF-2–, VEGF-A–, and VEGF-C–Induced Angiogenesis, Lymphangiogenesis, Vascular Fenestrations, and Permeability

Lymphedema Legislation Alert

Sending this to all my groups - important we act on this

Pat

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Robert Weiss, MS, NLN Legislative Patient Advocate

The recent change to the HCPCS coding of compression garments is a change that will have devastating impact on treatment of lymphedema patients in this country. By re-classifying these garments as "surgical dressings, secondary" they will no longer be covered for home use, and can no longer be billed as prosthetics (L-Code) and allowable under section 1861(s)(8) of the Social Security Act. This Medicare action will deprive an estimated 1.3-million lymphedema sufferers under Medicare, and by extension, other millions under HMO or private insurance, of the medically necessary treatment tool required in the daily care of their lymphedema.

I have already heard from one Medicare "beneficiary" who, after many years of receiving compression garments for his lymphedema, was notified that he will no longer receive compression garments for treatment of his lymphedema, based on the recent code change.

We must write to our Congressional representatives protesting this change of coding which has no basis either in Medicare law or medicine, which was not opened to medical or legal discussion, and which will potentially result in an increase in Medicare costs to treat cellulitis resulting from under-treatment of lymphedema. A National Coverage Decision on the subject of lymphedema treatment is long overdue. Also ask them whether they have considered sponsoring the "Lymphedema Diagnosis and Treatment Cost Saving Bill" which has been proposed widely in Washington over the last four years by this writer.

For questions or concerns, please contact Robert (“Bob”) at lymphactivist@aol.com.

Imaging of lymphatic vessels in breast cancer-related lymphedema: intradermal versus subcutaneous injection of 99mTc-immunoglobulin.

AJR Am J Roentgenol. 2006 May;186(5):1349-55.
O'Mahony S, Solanki CK, Barber RW, Mortimer PS, Purushotham AD, Peters AM.

Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge, UK.

OBJECTIVE:

The disordered physiology that results from axillary lymph node clearance surgery for breast cancer and that leads to breast cancer-related lymphedema is poorly understood. Rerouting of lymph around the axilla or through new pathways in the axilla may protect women from breast cancer-related lymphedema. The aim of the study was to compare intradermal with subcutaneous injection of technetium-99m ((99m)Tc)-labeled human polyclonal IgG (HIG) with respect to lymphatic vessel imaging.

MATERIALS AND METHODS:

Six women with breast cancer-related lymphedema underwent unilateral upper limb lymphoscintigraphy, using a web space injection of (99m)Tc-labeled HIG, after intradermal and subcutaneous injections on separate occasions. Multiple sequential images were obtained of the affected upper limb and torso over 3 hr on each occasion. Accumulation of activity in blood was quantified from venous blood samples taken from the opposite arm.

RESULTS:

Imaging after intradermal injection clearly showed discrete lymphatic vessels in five of six patients, in contrast to imaging after subcutaneous injection, which did not show any discrete vessels in any patient. Intradermal injection resulted in more rapid visualization of cutaneous lymph rerouting than subcutaneous injection in six of six patients. Recovery of injected (99m)Tc-labeled HIG in venous blood was greater after intradermal injection in six of six patients.

CONCLUSION:

In patients with breast cancer-related lymphedema, lymphatic vessels are more clearly depicted after intradermal than subcutaneous injection as a result of direct access of radiotracer to dermal lymphatics. This finding has implications for imaging lymphatic vessel regeneration and lymph rerouting.

PMID: 16632730 [PubMed - in process]

Indirect magnetic resonance lymphangiography in patients with lymphedema Preliminary results in humans.

Eur J Radiol. 2006 Apr 16; [Epub ahead of print]

Lohrmann C, Foeldi E, Langer M.Division of Diagnostic Radiology, Department of Radiology, University Hospital of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.

PURPOSE:

To assess the feasibility of indirect magnetic resonance (MR) lymphangiography with intracutaneous injection of gadodiamide, a commercially available, non-ionic, extracellular paramagnetic contrast agent for the detection of lymphatic vessels in patients with lymphedema.

MATERIALS AND METHODS:

In 2005, three patients with lymphedema of the lower extremities (1 primary, 2 secondary) were referred by the Foeldi Clinic for Lymphology for indirect magnetic resonance lymphangiography. 4.5mL of gadodiamide and 0.5mL of mepivacainhydrochloride 1% were injected intracutaneously into the dorsal aspect of each foot. MR imaging was performed with a 1.5-T system equipped with high-performance gradients. For indirect magnetic resonance lymphangiography, a 3D Fast Low Angle Shot (FLASH) sequence (TR/TE: 5.1/1.23; flip angle: 25; matrix: 448x448; bandwidth: 330Hz/pixel; 6/8 rectangular field of view with a maximum dimension of 500mm; slices: 88; voxel size: 2.0mmx1.0mmx1.0mm; acquisition time: 0min 31s) was used.

RESULTS:

Indirect magnetic resonance lymphangiography depicted lymphatic vessels of the lower and upper leg, and inguinal lymph nodes in all three patients. After 5min of contrast material application, concomitant venous enhancement was detected. Collateral vessels with dermal back-flow were seen in two patients. A lymphocele in the inguinal region with the afferent lymphatic vessel was depicted in one patient.

CONCLUSION:

In the presented small study group, indirect magnetic resonance lymphangiography was technically feasible, and no complications were observed after intracutaneous injection of gadodiamide. Visualizing the lymphatic vessels and accompanying complications non-invasively and without the use of radiation, the presented method has the capability to become a routine diagnostic imaging tool in patients with primary and secondary lymphedema. The method is not able to characterize lymph node morphology, but could provide additional information about the lymphatic vessels when lymph nodes are examined, e.g. with super-paramagnetic iron oxide particles.

PMID: 16621396 [PubMed - as supplied by publisher]