A longer duration of polymyxin B-immobilized fiber column hemoperfusion improves pulmonary oxygenation in patients with septic shock.

Endotoxin plays an important role in the pathogenesis of septic shock. Exposure of endothelial cells to endotoxin activates endothelial cells and increases the surface expression of adhesion molecules, markers of endothelial damage in organ dysfunction. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column (PMX) hemoperfusion has been used for the treatment of septic shock patients. In this study, we measured plasma concentrations of endotoxin and soluble adhesion molecules in septic shock patients before and after the PMX treatment then observed on the relationships between actual duration of use and various outcomes. Sixteen patients with septic shock were studied. The 28-day mortality rate was 50%. The elevated plasma concentrations of endotoxin decreased after the PMX treatment in the survivors but not in the nonsurvivors. The norepinephrine dose and plasma concentrations of soluble endothelial leukocyte adhesion molecule 1 and soluble intercellular adhesion molecule 1 significantly (P < 0.05) decreased in the PMX greater-than-2-h (prolonged) group than in the PMX 2-h (conventional) group (-17.8 +/- 14.6 vs. -1.8 +/- 2.7 microg/min, -143.0 +/- 111.0 vs. 0 +/- 2.8 ng/mL, and -126.2 +/- 144.9 vs. 16.5 +/- 108.1 ng/mL, respectively). Changes in the PaO2-FiO2 ratio and the Sequential Organ Failure Assessment score were significantly (P < 0.05) more improved in the PMX greater-than-2-h group than in the PMX 2-h group (75.4 +/- 80.7 vs. 1.2 +/- 49.2 and -0.8 +/- 1.8 vs. 2.2 +/- 1.9 torr, respectively). We thus suggest that a longer duration of PMX treatment may improve the pulmonary oxygenation associated with decreased adhesion molecules in septic shock.

[Superficial small cell carcinoma of esophagus treated by endoscopic mucosal resection combined with chemoradiotherapy--a case report].

The patient was a 70-year-old woman who was admitted to our hospital for positive fecal occult blood. Upper gastrointestinal endoscopy revealed a superficial plateau-type (0- I sep) submucosal cancer on the right wall of the esophagus 28 cm from the incisor. Biopsy revealed small cell carcinoma. CT scan detected neither lymph node metastasis, nor distant organ metastasis. Endoscopic mucosal resection (EMR) was performed. Post-EMR chemoradiotherapies were conducted. The patient has lived with no evidence of cancer recurrence for 40 months. This was the first case of esophageal small cell carcinoma treated by EMR combined with chemoradiotherapy.

The expressions of p21 and pRB may be good indicators for the sensitivity of esophageal squamous cell cancers to CPT-11: Cell proliferation activity correlates with the effect of CPT-11.

Previously, we demonstrated that CPT-11 is an effective agent against esophageal squamous cell cancers (ESCC), and that the protein level of DNA topoisomerase I can be a predictor for sensitivity to CPT-11 (Jpn J Cancer Res 2001; 92: 1335-41). Here, we describe our search for additional predictors of sensitivity to CPT-11, mainly among cell cycle-regulating proteins, because the cytotoxicity of CPT-11 is significantly correlated with the percentage of ESCC cells in S-phase. To this end, we selected and examined the expressions of 5 proteins involved in G1-S transition, i.e., p53, cyclin D1, p21, p27, and pRB, in 14 ESCC cell lines by western blot analysis. Among these proteins, the expression levels of p21 and pRB showed significant differences that were associated with the IC50 values for CPT-11 (P = 0.0339 and P = 0.0109, respectively). Namely, the expression of p21 or pRB independently could be a good indicator of CPT-11 efficacy in ESCC. In addition, the cell proliferation activities examined by enzyme-linked immunosorbent assay (ELISA) using 5-bromo-2'-deoxyuridine (BrdU) showed a significant correlation with the percentage of total S-phase cells (correlation coefficient = 0.568, P = 0.0324), and an inverse correlation with the IC50 values for CPT-11 (correlation coefficient =-0.601, P = 0.0213). Because, as in the case of DNA topoisomerase I, the cell proliferation activity determined using BrdU shows a close relationship with the MIB-1 labeling index, immunohistochemical studies of p21, pRB, and MIB-1 in resected ESCC specimens and/or biopsy samples could make it possible to predict more precisely the sensitivity of ESCC patients to CPT-11 prior to treatment.