Ultrasound-guided foam sclerotherapy as a therapeutic modality in venous ulceration.

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate rates of ulcer healing following ultrasound-guided foam sclerotherapy (UGFS). METHODS: The MEDLINE, CENTRAL and Embase databases were used to search for relevant studies using the terms ' (sclerotherapy AND ulcer) OR (vein AND ulcer) OR (sclerotherapy AND vein)'. Heterogeneity between studies was quantified using the I2 statistic. A random effects model was used to calculate risk ratios where substantial heterogeneity was found. RESULTS: The initial search yielded 8266 articles. 8 studies were included in the qualitative synthesis and 3 in the meta-analysis. Superior complete ulcer healing rates were noted in patients treated with foam sclerotherapy versus compression therapy alone (pooled OR 6.41, 95% CI = 0.3-148.2, p = 0.246, random effects method). A marked degree of heterogeneity was observed between studies (I2 = 81%). CONCLUSION: A prospective, trial is warranted in order to determine the true merits of UGFS in the setting of venous ulceration.

Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer.

Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.

Altered response to and production of TGF-beta by B cells from autoimmune NZB mice.

New Zealand Black (NZB) mice spontaneously develop immune dysfunction manifested as autoimmune hemolytic anemia and systemic lupus erythematosus. In later life, a subset of these mice develop clonal CD5+ B cell tumors analogous to human chronic lymphocytic leukemia (CLL). NZB disease is marked by B cell hyperactivity characterized by spontaneous immunoglobulin secretion and proliferation. Elimination of autoreactive lymphocytes by apoptosis is a vital mechanism to prevent expansion of self-reactive lymphocyte population. TGF-beta appears to be an important factor in normal and abnormal immune regulation and this cytokine may play a role in the development of chronic human B cell tumors. We asked whether the response to or production of TGF-beta by NZB B cells was aberrant and could contribute to disease development. In this study, we demonstrated that the apoptotic response to TGF-beta was increased in B cells from NZB mice compared to B cells from normal BALB/c mice. The increased apoptosis was related to endogenous activation and was possibly mediated through increased expression of the TGF-beta Type II receptor. Despite functional differences between CD5-negative B cells and CD5-positive B cells, TGF-beta induced apoptosis in both populations to a similar extent. NZB B cells also secrete increased active TGF-beta compared to BALB/c B cells. We suggest that the aberrant secretion of active TGF-beta and the increased response to the apoptotic effects of TGF-beta by NZB B cells may play a role in the disease process of these mice, perhaps attempting to limit the autoimmune phenomena, but possibly also contributing to generalized immunosuppression. We also suggest that the CD5(+) tumors in the NZB mouse may not be a fully appropriate model of human CLL, since CLL B cells are abnormally resistant to the apoptotic effects of TGF-beta.