Pentosan polysulfate decreases proliferation and extracellular matrix deposition by vascular smooth muscle cells isolated from failed hemodialysis access grafts.

BACKGROUND: Vascular access failure is a major cause of morbidity, and increased costs in patients undergoing maintenance hemodialysis. Stenosis, the most common underlying cause of loss of patency in failed grafts, appears to be caused by an obstructing mass of tissue containing proliferating smooth muscle cells and their associated extracellular matrix. METHODS: To determine whether this process was amenable to pharmacologic intervention and/or prevention, we obtained samples of the material occluding vascular accesses from 7 patients undergoing revision surgery in order to characterize the cells contributing to the stenosis. In all 7 patients the outgrowth contained predominantly smooth muscle-like cells admixed with fibroblasts, which produced a large amount of type IV and type I collagen. RESULTS: Treatment with pentosan polysulfate inhibited cell proliferation and significantly reduced the accumulation of types I and type IV collagens. This was associated with increase in metalloproteinase-9 (MMP-9) and a shift of tissue inhibitor of metalloproteinase-3 (TIMP-3) from the cell layer into the medium. CONCLUSION: These data suggest that pentosan polysulfate (PPS) may have a favorable effect in patients with a polytetrafluoroethylene (PFTE) graft by decreasing cell proliferation and collagen deposition.

Importance of surgical resection in the successful management of soft tissue sarcoma.

HYPOTHESIS: A systemic disease-free state necessitates a local disease-free state. This cannot be accomplished without a properly performed resection by an experienced surgical team. Successful local management of soft tissue sarcoma (STS) may lead to improved disease-free survival. An STS treatment protocol using wide local excision followed by radiation therapy is effective in achieving local tumor control and survival similar to that of multiple-modality regimens, but with lower morbidity. DESIGN: Retrospective cohort review (August 1, 1987, to May 6, 1998). SETTING: Referral to a single musculoskeletal oncologic surgeon, with surgery performed at a tertiary care medical center in a large urban area. PATIENTS: Ninety patients with STS of the trunk or extremities. INTERVENTIONS: Preoperative evaluation included surveillance computed tomographic scan of the chest, magnetic resonance imaging of primary site to assess tumor extent and to plan the surgical approach, and angiography if vascular bypass was proposed. Wide local excision of tumor was performed, with concomitant vascular bypass and/or complex plastic reconstruction as needed. Postoperative radiation therapy was given in most patients. Adjuvant chemotherapy was used selectively. MAIN OUTCOME MEASURES: Morbidity, local recurrence rates, and survival. RESULTS: Histologically negative margins were obtained in 89 (99%) of 90 patients; 86 (96%) remained free of local disease at follow-up. Five patients died of systemic metastatic disease. CONCLUSION: Excellent local control obtained with aggressive, appropriate surgery followed by radiation therapy in most patients and chemotherapy in only selective high-risk patients leads to excellent survival, with low morbidity and good functional outcome.