Aesthetic outcomes in breast conservation therapy.

BACKGROUND: Since the National Surgical Adjuvant Breast and Bowel Project B06 (NSABP-B06) trial demonstrated equivalent survival outcomes between patients with breast cancer undergoing modified radical mastectomy versus lumpectomy and radiation, an increasing number of patients are seeking breast conservation therapy. Traditionally, only patients who have undergone total mastectomy have been referred for reconstruction. OBJECTIVE: The purpose of the study was to determine the number of dissatisfied patients treated with breast conservation therapy who have suboptimal cosmesis and should be referred for reconstruction. METHODS: After obtaining approval from the Institutional Review Board and patient consent, patients identified as more than 1 year posttreatment from breast conservation therapy (1999-2004) were interviewed and photographed. Data were gathered by use of a questionnaire that included patient aesthetic score, patient satisfaction, and change in body image. Photographs were shown to a surgical oncologist, a general surgeon, and a plastic surgeon for a physician aesthetic score. RESULTS: Thirteen of 46 patients (28.3%) were dissatisfied with their cosmetic result. Women who were dissatisfied with their cosmetic result were more likely to have a negative change in their body image when compared with patients who were satisfied with their cosmetic result (46.2 % vs 6.1%, P = .02). Additionally, dissatisfied patients were more likely to rate their cosmetic result as poor (15.4 % vs 0%, P = .007) and were more likely to consider reconstruction (46.2% vs 9.1%, P = .01) when compared with satisfied patients. Risk factors to predict dissatisfaction in our patient population included age younger than 52 years and the resection of tumor from the upper inner quadrant. CONCLUSIONS: Twenty-eight percent of patients in this study were dissatisfied with their cosmetic result. Furthermore, a large portion of these patients would consider reconstruction if it were offered. Although this study only identified a few broad risk factors for suboptimal cosmetic outcome, it confirms our hypothesis that many patients who have undergone breast conservation therapy should be referred for plastic surgery consultation.

Bovine hemoglobin-based oxygen-carrying solution (HBOC-201) improves flap survival in a rat model of epigastric flap failure.

Despite continued improvements in surgical technique and postoperative management of pedicled flaps, partial flap necrosis continues to be a substantial problem. Several researchers sought interventions that would decrease the incidence of this complication. The hypothesis of this study is that a bovine hemoglobin-based, oxygen-carrying solution (HBOC-201) will increase oxygen delivery, thus decreasing the area of necrosis of the marginally perfused portions of a pedicled flap. Eighty male Sprague-Dawley rats were randomly assigned to one of four groups (20 animals in each group): group 1, controls (surgical creation of flap only); group 2, HBOC-201, 2 g i.v., administered preoperatively and on days 3 and 5; group 3, HBOC-201, 4 g i.v., administered preoperatively and on days 3 and 5; and group 4, hemodilution (lactated Ringer's solution) administered preoperatively and on days 3 and 5. A ventral fasciocutaneous flap (5 x 7 cm) was elevated, based on unilateral superficial inferior epigastric vessels, and the flap was replaced and sutured. Animals were examined daily and euthanized on day 7. Prior to euthanasia, digital photographs were taken of each subject, and the images were analyzed for total area of the flap and area of necrosis, using ImagePro software. Using the calculated percentage of necrosis for each animal, a mean value of percent necrosis was obtained for each animal group and used for statistical analysis. Animals in group 2 demonstrated a decreased area of necrosis when compared with the control group (9.14% vs. 22.24%, P = 0.014). In conclusion, the oxygen therapeutic HBOC-201, at a dose of 2 g, administered preoperatively and on days 3 and 5, decreased the area of necrosis in a rat model of epigastric skin-flap failure. Further investigation of this drug and its effects on flap survival is warranted.

The effect of the bovine hemoglobin oxygen therapeutic HBOC-201 on human neutrophil activation in vitro.

BACKGROUND: We previously demonstrated that HBOC-201 is an efficient resuscitation fluid. However, little is known about its immunomodulatory effects. The goal of this study was to investigate human neutrophil activation after exposure to HBOC-201 and other low-volume resuscitation fluids. METHODS: Whole blood from 10 healthy volunteers was serially diluted with HBOC-201, 7.5% hypertonic saline (HTS), 7.5% hypertonic saline-6% dextran 70 (HSD), Hextend, or PentaLyte. After an incubation period, samples were analyzed for oxidative burst and CD11b expression using flow cytometry. RESULTS: Increases in both CD11b and oxidative burst activity were noted in samples diluted with HBOC-201, Hextend, PentaLyte, and lactated Ringer's solution. Samples maximally diluted with HBOC-201 demonstrated increased CD11b expression when compared with lactated Ringer's solution and Hextend (196.11% vs. 22.68% and 33.97%; p = 0.018 and p = 0.033). CONCLUSION: Although differences were noted only at the highest dilutions, further studies investigating the effects of HBOC-201 are warranted.

Endothelial dysfunction after arterial thrombosis is ameliorated by L-arginine in combination with thrombolysis.

PURPOSE: To assess endothelial function after arterial thrombosis creation and after administration of a novel thrombolytic regimen in a new porcine model. MATERIALS AND METHODS: Untreated arteries that had undergone thrombosis for 90 minutes were compared to arteries treated with tissue plasminogen activator (tPA, 4 mg) and a combination of tPA and L-arginine (L-arg; 600 mmol/L). External iliac artery luminal diameter was measured with use of duplex ultrasonography. Endothelial-dependent relaxation (EDR) and endothelial-independent relaxation (EIR) were measured with use of acetylcholine chloride (ACh) and sodium nitroprusside (NTP), respectively. Endothelial integrity was confirmed by scanning electron microscopy (SEM). Nitric oxide (NO) levels were determined with use of a chemiluminescent assay of its nitrite/nitrate metabolites (NO(x)). RESULTS: After thrombosis, EDR was decreased (69% +/- 9.5; ACh = 15 micro g/min; n = 6). EDR remained unchanged after thrombolysis with tPA despite complete dissolution of thrombus (67% +/- 5.7; ACh = 15 micro g/min; n = 5). Thrombolysis with use of tPA coupled with L-arg resulted in an increase in EDR (95% +/- 4.9; ACh = 15 micro g/min; n = 5; P =.007). EIR was preserved in all groups, with uniform response to NTP. SEM analysis revealed intact endothelium in all groups. Local NO(x) levels were diminished after 90 minutes of thrombosis (49.3 micro mol/L vs 40.8 micro mol/L; P =.0002), but increased to 55.7 micro mol/L after thrombolysis with tPA and L-arg (P = NS). CONCLUSIONS: Thrombus induces arterial dysfunction acutely without altering endothelial integrity. This dysfunction is ameliorated through regional administration of L-arg in combination with standard thrombolytic therapy, which increases local NO levels. This model allows the in-vivo study of thrombosis and alternative thrombolytic regimens. Regional enhancement of NO levels may prove to be an attractive adjunct in thrombolytic therapy.

Luminal thrombus disrupts nitric oxide-dependent endothelial physiology.

BACKGROUND: The goals of this study were: (1) to develop a large animal model to study endothelial function, and (2) to determine if arterial thrombosis induces endothelial dysfunction in vivo. METHODS: Surgical exposure of the porcine iliac and femoral arteries was performed. Normal porcine arteries were compared with arteries subjected to 90 min of arterial thrombosis. External iliac artery (EIA) luminal diameters were measured using M- and B-mode duplex ultrasound. Endothelium-dependent relaxation (EDR) and endothelium-independent relaxation (EIR) were measured using acetylcholine (ACh) and sodium nitroprusside (NTP), respectively. Endothelial integrity was determined by factor VIII immunohistochemistry (F8) and scanning electron microscopy (SEM). Nitric oxide levels were determined using a chemiluminescence assay of nitrite/nitrate metabolites (NO(x)). Continuous variables were analyzed using the two-tailed Student t test. RESULTS: Control artery EDR was 80 +/- 7.1% (+/- SE), while arteries exposed to luminal thrombus for 90 min had an EDR of 55.2 +/- 5.7% (ACh = 15 microg/min, n = 11, P = 0.0231). EIR was preserved in normal and thrombosis groups with uniform response to NTP (4.92 +/- 0.1 cm vs 5.07 +/- 0.42 cm, P = 0.76). F8 staining identified endothelium in all groups. SEM analysis revealed an intact monolayer of endothelium after thrombosis. Local NO(x) levels were 17.3% lower after 90 min of thrombosis (49.3 microM vs 40.8 microM, n = 16, P < 0.001). CONCLUSIONS: Luminal thrombus induces arterial dysfunction acutely without causing endothelial cell loss. EIR remains unaffected, indicating normal smooth muscle cell function. NO(x) levels suggest that nitric oxide levels are decreased acutely after thrombosis. The development of this porcine large animal model allows the in vivo study of vasospasm and alternative thrombolytic regimens.

The polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) is not toxic to neural cells in culture.

BACKGROUND: Recent data suggest that a neurotoxic effect of blood or its components may contribute to secondary neural cell dysfunction. This study investigated the effects of HBOC-201 (Hemopure) and purified human hemoglobin (hHgb) on rat fetal neural cell culture. METHODS: Neural cell cultures were exposed to HBOC-201 and hHgb (0.02, 0.2, 2.0, and 6.5 g/dL) for 24 hours, and then analyzed for proliferation, metabolism, and neurolysis. RESULTS: Cultures exposed to HBOC-201 maintained levels of proliferation and metabolism similar to controls while demonstrating no cellular lysis. However, cultures exposed to hHgb demonstrated decreased proliferation after exposure to 0.2, 2.0, and 6.5 g/dL hHgb (14,252.14, 3,221.89, and 343.12 vs. 19,509.53; p< 0.05) when compared with controls. In addition, cultures exposed to hHgb demonstrated decreased metabolic activity and increased cell lysis when compared with controls (p < 0.05). CONCLUSION: Cultures exposed to HBOC-201 displayed sustained metabolic activity and proliferation, and demonstrated no neurolysis, suggesting that HBOC-201 does not display the toxic characteristics of hHgb.