Stage II esophageal carcinoma: the significance of T and N.

OBJECTIVE: Stage II esophageal carcinomas are a heterogeneous group of uncommon malignant tumors that include both node-negative (IIA; T2 N0 M0 and T3 N0 M0) and node-positive (IIB; T1 N1 M0 and T2 N1 M0) carcinomas. The purpose of this study was to evaluate this heterogeneity and to identify predictors of improved survival. RESULTS: Ninety-four of 345 patients undergoing esophageal resection at the Cleveland Clinic Foundation between 1985 and 1994 had stage 11 carcinomas; 70 stage IIA (24 T2 N0 M0 and 46 T3 N0 M0) and 24 stage IIB (9 T1 N1 M0 and 15 T2 N1 M0). Pathologic stage and T and N status were the only identifiable predictors of survival. Stage IIA survival was significantly better than stage IIB (p = 0.01). T2 N0 M0 survival was not different from T1 N0 M0 survival (p = 0.83). T3 N0 M0 survival was significantly worse than T1 N0 M0 (p = 0.03) and intermediate between T2 N0 M0 survival (p = 0.06) and T1 N1 M0 and T2 N1 M0 survivals (p = 0.07). T1 N1 M0 and T2 N1 M0 survival was not significantly different from T3 N1 M0 survival (p = 0.63). CONCLUSIONS: (1) N1 disease is the principal predictor of reduced survival and N1 is independent of T. Therefore the distinction between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas is not warranted. (2) N0 disease is the principal predictor of improved survival but N0 is not independent of T. T1 N0 M0 and T2 N0 M0 survivals are similar and therefore distinction between these subgroups is not warranted. T3 N0 M0 survival is intermediate between T1 N0 M0 and T2 N0 M0 carcinomas and between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas. Therefore stratification by T for N0 carcinomas is warranted.

Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model.

Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model.

Endothelial cell preservation using organ storage solutions.

The development of organ preservation solutions has been primarily accomplished in whole organ animal models. This study examines the toxicity of commonly used organ preservation solutions on endothelial cells in vitro. Primary human umbilical-vein endothelial cell cultures were incubated at 4 degrees C in solutions of 0.9% saline (NS), EuroCollins, ViaSpan (Belzer UW) (VIA), or Hank's balanced salts with 5% polyethylene glycol (PEG). Endothelial cell viability was ascertained by colormetric measurement of mitochondrial reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to purple 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan. After exposure to hypothermic storage, cells were incubated at 37 degrees C in media with MTT, and the amount of reduced formazan present was quantified using a micro-ELISA spectrophotometer. Higher absorbance values were indicative of better cellular preservation. Cells stored in PEG displayed the highest viability at all time periods. ViaSpan provided better cellular protection than EC at longer storage intervals. This model allows for rapid assessment of preservation-induced endothelial cell injury and may aid development of improved storage techniques.

Improvement of endothelial cell viability at 4 degrees C by addition of lazaroid U74500A to preservation solutions.

Lazaroids are potent inhibitors of lipid peroxidation. Endothelial cell damage has been shown to occur during cold storage preservation of lung and liver. This study examines the effects on endothelial cell viability of the addition of four lazaroids, U74006F, U78518F, U74500A, or U75412E to preservation solutions. Human umbilical vein endothelial cell cultures were stored at 4 degrees C for 48 and 96 hr in EuroCollins or 5% polyethylene glycol in buffered saline (PEG). U78518F, U74500A, U74006F, U75412E, or dexamethasone (each 50 microM) was added to EC (n = 32) or PEG (n = 32) and compared with control solutions of EC or PEG alone. Endothelial cell viability was determined by measuring cellular reduction of 3-[4,5-dimethylthiazol-2-yl]-2,3-diphenyltetrazolium bromide to a purple formazan dye. The reduction occurs only in viable cells and requires mitochondrial dehydrogenase activity. Results were quantified by measuring dye absorbance (Ab) with a micro-ELISA spectrophotometer. Absorbance values were compared by ANOVA and reported as mean values +/- standard deviation. Addition of U74500A to EC (Ab = 0.474 +/- 0.055) and PEG (Ab = 0.462 +/- .005) improved viability at 48 hr when compared with EC (Ab = 0.289 +/- 0.069) and PEG (Ab = 0.287 +/- 0.052) alone (P less than 0.05). At 96 hr, addition of U74500A resulted in improved viability in both EC (Ab = 0.377 +/- 0.068) and PEG (Ab = 0.195 +/- 0.09) or PEG alone (Ab = 0.212 +/- 0.1) (P less than 0.05). Other lazaroids tested were also effective in improving cellular viability, but to a lesser degree than U74500A. This study demonstrates that the addition of lazaroids to organ preservation solutions improves endothelial cell viability.

Flow cytometric analysis of organ preservation-induced endothelial cell membrane damage.

Organ preservation for transplantation is associated with endothelial cell damage. This vascular injury results in increased capillary permeability, graft edema, and early graft dysfunction. This damage may be the limiting factor in preservation of these organs. This study uses flow cytometric assessment of membrane integrity to examine the effects of various organ preservation solutions on human umbilical vein endothelial cell cultures. Confluent plates of human umbilical vein endothelial cells were incubated at 4 degrees C for 24, 48, and 72 hours in commonly used preservation solutions. After cold incubation, the cells were harvested and stained with propridium iodide and fluorescein diacetate. Cells were examined using a flow cytometer for membrane integrity and cytosolic activity. When examined after 24, 48, and 72 hours, cells stored at 4 degrees C in a 5% polyethylene glycol salt solution were significantly less damaged than those stored in any other solution (p less than 0.05). After 48 and 72 hours at 4 degrees C, cells stored in ViaSpan were significantly more intact than cells stored in EuroCollins and 0.9% saline solution (p less than 0.05). This study demonstrates that endothelial cell damage occurs during cold storage and that a polyethylene glycol-based solution showed superior cellular preservation.

Anterolateral thoracotomy as an alternative to repeat median sternotomy for replacement of the mitral valve.

Median sternotomy is the most common approach for repeat cardiac surgery despite the potential complications of cardiac injury. Right anterolateral thoracotomy has been recommended as an alternative for patients undergoing mitral valve replacement, but data supporting one approach over the other do not exist. To compare these procedures, the records of 43 patients who had had a previous median sternotomy and who underwent mitral valve replacement were reviewed. No statistically significant differences between patients undergoing repeat median sternotomy (33 patients) and those undergoing right anterolateral thoracotomy (10 patients) were demonstrable when compared for age, gender, New York Heart Association Functional Class, other diseased valves, urgency of operation, indication for operation, type of valve removed, type of valve implanted, length of postoperative hospitalization, length of operation, days of ventilatory support, length of intensive care unit stay, and survival (90% for thoracotomy group; 76% for median sternotomy group; p, NS). Significant differences between the two groups, favoring right anterolateral thoracotomy, were apparent when comparisons were made for length of perfusion (means, 94.8 min, thoracotomy group; 121.4 min, sternotomy group; p = .03), incidence of reexploration (0%, thoracotomy group; 13%, sternotomy group; p = .001), and blood transfusion (means, 5.3 units, thoracotomy group; 11.4 units, sternotomy group; p = .003). Right anterolateral thoracotomy is an effective alternative to repeat median sternotomy for replacement of the mitral valve in patients who have had a previous median sternotomy.