Persistent elevated C-reactive protein after treatment is an independent marker of a poor prognosis in patients with hepatocellular carcinoma.

PURPOSE: The pretreatment C-reactive protein (CRP) level is reported to be a prognostic indicator in patients with hepatocellular carcinoma (HCC). METHODS: We investigated the prognostic implications of the changes in the CRP level after initial treatment in patients with HCC. We prospectively evaluated a cohort of 150 patients with newly diagnosed HCC. The patients were categorized into three groups: group 1 (n = 120) with pre- and post-treatment CRP <1.0 mg/dl, group 2 (n = 5) with pre-treatment CRP ≥1.0 mg/dl and post-treatment CRP <1.0 mg/dl, and group 3 (n = 25) with pre- and post-treatment CRP ≥1.0 mg/dl. RESULTS: The 1- and 3-year overall survival rates were 92.3 and 82.9 % for group 1, 80.0 and 53.3 % for group 2, and 58.8 and 4.2 % for group 3. The overall survival rate for group 3 was significantly lower than that for group 1 (P < 0.0001), or group 2 (P = 0.003). No significant difference was found between groups 1 and 2 (P = 0.627). A multi-variate analysis showed that albumin level (P = 0.049), the CRP group (P < 0.0001), and the Cancer of the Liver Italian Program (CLIP) score (P < 0.0001) were independently associated with the overall survival. CONCLUSIONS: A persistently elevated CRP level after initial treatment is an independent marker of a poor prognosis, and normalization of the CRP level after initial treatment is associated with a better outcome in patients with HCC.

Gut ischemia/reperfusion produces lung injury independent of endotoxin.

OBJECTIVE: Bacterial translocation from the gut has been invoked as a common inciting event for postinjury multiple organ failure. We previously showed that gut ischemia/reperfusion induces remote organ injury. The purpose of this study was to ascertain if endotoxin has a pivotal mechanistic role in this process. DESIGN: Prospective, randomized study. SETTING: Animal laboratory. SUBJECTS: Sprague-Dawley rats weighing 300 to 350 g. INTERVENTIONS: Anesthetized animals underwent 45 mins of superior mesenteric artery occlusion and 2 hrs of reperfusion; sham laparotomy served as controls. Endotoxin was eliminated with the murine immunoglobulin (Ig) M antibody E5, 3 mg/kg i.v. before the study. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin was measured by the limulus amebocyte lysate assay. At 2 hrs of reperfusion, circulating neutrophil priming was determined by the difference in superoxide generation with and without the activating stimulus, N-formyl-Met-Leu-Phe. Neutrophil sequestration in the lung was quantitated by myeloperoxidase activity, and by lung endothelial permeability by 125I albumin lung/blood ratio. Endotoxin concentrations were not significantly (significance determined as p < .05) different between the gut ischemia/reperfusion and laparotomy groups (n = > or = 5) during ischemia or reperfusion. Circulating neutrophil priming, neutrophil accumulation in the lung, and lung injury were provoked by gut ischemia/reperfusion, but not altered by endotoxin elimination. CONCLUSION: Gut ischemia/reperfusion primes circulating neutrophils and produces lung injury by a mechanism independent of endotoxin.

Requirement for thrombin receptor occupancy during platelet secretion under aggregating and non-aggregating conditions.

The requirement for receptor occupancy in thrombin-induced secretion in human platelets has been studied. When increasing concentrations of thrombin were added to gel-filtered platelets containing a constant, high concentration of hirudin, dense granule secretion was initiated at lower thrombin concentrations than those required for alpha-granule secretion and aggregation; acid hydrolase secretion required higher concentrations. A 62-fold excess of hirudin produced abrupt stop of dense granule secretion and alpha-granule secretion when added to non-aggregating (no stirring) platelets shortly after thrombin; it had no affect after these secretory process had reached about 30% of their maximal values. Acid hydrolase secretion was, however, abruptly stopped by hirudin at any stage. When the platelets were allowed to aggregate, the three secretory processes increased their rates and were abruptly stopped by hirudin at any stage. Aggregation (optical) occurred slower than dense granule and alpha-granule secretion, and was reversed by hirudin when added before it had reached 30% of its maximum. It is concluded that alpha-granule secretion, like dense granule secretion, only requires a short receptor occupancy to be completed, in contrast to the requirement for sustained occupancy for acid hydrolase secretion. alpha-Granule secretion might, however, require longer occupancy than dense granule secretion. Aggregation is believed to potentiate secretion through close cell contact and the secretion processes were inhibited by hirudin through hirudin's effect on aggregation.