Showing papers by "Stanley G. Rockson published in 2002"

Therapeutic lymphangiogenesis with human recombinant VEGF-C

Abstract: SPECIFIC AIMChronic postsurgical lymphedema, typically acquired as an iatrogenic consequence of therapy for breast or pelvic malignancies, is an ideal candidate for targeted gene therapy to elicit therapeutic, regenerative growth of lymphatic vasculature. Accordingly, we developed a model for this disorder in the rabbit ear in order to investigate the therapeutic potential for lymphangiogenesis with exogenously administered human recombinant VEGF-C.PRINCIPAL FINDINGS1. Segmental surgical resection of the lymphatic vasculature at the base of a single ear was well tolerated in all experimental subjects and yielded chronic, stable edema in 16 of the 18 subjectsThe increase in ear volume as measured by water displacement volume averaged 56% (range, 12.5–115%). When compared with volumes of the nonoperated ears, these increases in volume were highly significant (P<0.0001). Of these 16 rabbits, 8 were treated with a single 100 μg dose of recombinant VEGF-C; the remaining 8 received a comparable volume of inject...

Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity.

Abstract: Secondary lymphedema is a localized, acquired lymphatic microcirculatory disturbance that affects large numbers of patients after breast cancer therapy. There is a paucity of objective methods to quantitate lymphatic function and to anticipate the response to therapeutic interventions. We applied radionuclide lymphoscintigraphy to evaluate lymphatic transport and axillary lymph node visualization in women following breast cancer therapy to determine the utility of these data in these patients. Lymphoscintigraphy was performed after subcutaneous injection of 0.25 mCi of 99m Tc-filtered sulfur colloid. Subcutaneous accumulation of radiotracer ('dermal backflow') and the visualization of axillary lymph nodes were graded using our own scoring system. The ratio of radioactivity within the affected to normal axillae (ARR) was also quantified. Nineteen patients with lymphedema after breast cancer therapy were evaluated. The disease severity was documented by serial measurements of the limb volume using the truncated cone formula. Responses to therapy were quantified after completion of the therapy. There was a correlation between the ARR and the percentage reduction in edema volume. The lymphoscintigraphic score correlated with the initial arm volume excess and with the duration of lymphedema. It can be concluded that quantitative and semi-quantitative assessment by radionuclide lymphoscintigraphy represents a potentially useful tool for the clinical assessment of upper extremity lymphedema.

Preclinical Models of Lymphatic Disease

Abstract: The human disease states that are characterized by functional lymphatic insufficiency currently lack a cure. Molecular approaches may ultimately provide a therapeutic window to reverse the stigmata of both primary and secondary lymphatic insufficiency. To harness the potential therapeutic power of lymphangiogenesis, testing the safety and efficacy of the treatment response will be necessary. This, in turn, necessitates the availability of suitable preclinical animal models of the disease processes in question, along with suitable research tools to permit an assessment of the response to applied therapies. An ideal model would reproducibly and inexpensively replicate the untreated disease of human lymphedema. It would closely simulate the biology, as we understand it, of the human disease, and would replicate both the pathogenesis of the disease, including its natural history and the temporal patterns of its clinical expression. In this way, one might aspire to make valid predictions about the human applicability of therapy by extrapolation from observations in animal models. In addition to the availability of suitable animal models, the required investigative tools must also be available. In the context of lymphangiogenesis, to assess the therapeutic response, one must certainly possess the ability to recognize newly developed lymphatic vasculature. Sophisticated immunohistochemical and imaging techniques make this increasingly feasible. Initial experimental observations indicate that growth factor and gene therapy with VEGF-C holds promise for the treatment of both primary and secondary forms of lymphedema.

Lymphedema After Surgery for Cancer

Abstract: Lymphedema remains a relatively common, and often under-recognized, complication of breast cancer therapy. When present, arm edema can engender significant morbidity and psychological distress in survivors of breast cancer. Therapeutic approaches to post-mastectomy lymphedema further compromise mental health because of the unrelenting demands on patient time and energies. It is proposed that psychoeducational interventions, including supportive group therapy, would be helpful. Although formal outcomes studies are lacking, extrapolation from studies of more broadly defined groups of people surviving cancer suggest that this approach might be useful to further acceptance of preventive strategies, diminish social isolation, and provide more effective coping skills.