Limb-sparing surgery with vascular reconstruction for malignant lower extremity soft tissue sarcoma.

BACKGROUND: The standard of care for lower extremity soft tissue sarcoma (STS) is limb-sparing surgery. A small subset of these patients will require concomitant vascular reconstruction to ensure adequate resection and to preserve limb viability and function. The aim of this study was to evaluate outcomes in these patients with respect to wound healing and postoperative functional status. METHODS: Outcomes for a total of 154 patients treated for malignant lower extremity STS during an 8-year period between 2005 and 2013 were entered in a prospective registry. Treatment was by medical management in 3 patients (2%), limb-sparing surgery with vascular reconstruction (LSVR) in 9 patients (6%), and limb-sparing surgery without vascular reconstruction (LS) in 142 patients (92%). The registry and patient records and the intraoperative records were consulted to determine the primary outcomes of patient survival and time for complete wound healing. The functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) functional assessment score before surgery and at 6 and 12 months after surgery. RESULTS: Mean follow-up time was 74.7 months for the LSVR group and 53.4 months for the LS group. The mean time to complete wound healing was significantly longer in LSVR vs LS patients (88 days vs 34 days, respectively; P = .002), and overall survival was lower in LSVR patients (P = .01). Seven of the 9 LSVR patients required a total of 12 additional procedures to achieve wound healing, including 9 procedures to drain seromas (incision and drainage) with vacuum-assisted closure in 4 cases. Plastic surgery intervention was required in three patients, including one skin graft, one gracilis pedicle flap, and one vertical rectus abdominis myocutaneous flap. There was no significant difference in the mean MSTS scores preoperatively, at 6 months, and at 1 year after surgery between the two groups (27, 25, and 29 for LSVR vs 28, 31, and 31 for LS, respectively; P = .63, .11, and .67, respectively). CONCLUSIONS: The need for vascular reconstruction during limb-sparing surgery for lower extremity malignant STS is rare in a high-volume sarcoma center. Overall survival was lower in these patients, and the time to complete wound healing is prolonged and requires multiple secondary interventions. However, postoperative functional status as assessed by the MSTS is acceptable and comparable to that of patients not requiring vascular reconstruction.

Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension.

This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the "Warburg effect"), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension.

Captopril treatment temporarily restores cerebral blood flow autoregulation in spontaneously hypertensive rats after hemorrhagic stroke.

Hemorrhagic stroke development in stroke-prone spontaneously hypertensive Kyoto Wistar rats (SHRsp) is associated with a loss of cerebral blood flow (CBF) autoregulation and death. We assessed the ability of poststroke captopril treatment to retard death and restore CBF autoregulation in SHRsp. Laser Doppler techniques were used to measure alterations in CBF with varying mean arterial pressure (MAP) in anesthetized SHRsp. Three weeks before stroke, all SHRsp autoregulated near constant CBF to an upper MAP limit of 155 +/- 4 mm Hg. CBF autoregulation was absent in half of the SHRsp at 0.5-2 weeks before stroke and nonexistent in SHRsp with stroke. Captopril treatment (50 mg kg(-1) d(-1)) initiated at the first signs of stroke (seizures) increased the lifespan of SHRsp from 10 +/- 3 to 124 +/- 18 days without lowering blood pressure and restored CBF autoregulation within 10 days. CBF autoregulation subsequently deteriorated where after 25 days of treatment, only 2 of 5 SHRsp maintained the ability to autoregulate CBF. We concluded that captopril treatment retarded death and new hemorrhage formation after stroke. The early restoration of autoregulation could prevent sudden death after stroke, but other mechanisms associated with poststroke captopril treatment act to prolong life in the presence of hypertension and absence of CBF autoregulation.