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The liver is the organ most commonly injured during blunt abdominal trauma. As our society ages, emergency surgery for active elderly patients increases, but data on aggressive emergency hepatic resection remain scarce in the literature. The purpose of this study was to determine whether the elderly (70 years of age or older) can tolerate major liver injury and subsequent hepatic resection. We investigated 100 patients who were treated by an anatomic resection for severe blunt liver trauma (29 elderly patients who were 70 years of age or older and 71 young patients who were younger than 70 years of age) in a retrospective study. The elderly patients were more severely injured as demonstrated by a higher Injury Severity Score, a lower Glascow Coma Scale, and lower survival (80.3% vs. 65.5%; p < 0.05). The total number of associated injuries was greater in elderly patients. Motor vehicle accidents were responsible for 71.8% of the injuries in the young group, and the predominant mechanism in the elderly patients was also motor vehicle accidents (51.7%). The 71 anatomic hepatic resections performed on the young patients included right hemihepatectomy (n = 45), left lateral segment resection (n = 14), bisegmentectomy (n = 5), and others. The 29 anatomic hepatic resections performed for the elderly patients were right hemihepatectomy (n = 15), left lateral segment resection (n = 5), left hemihepatectomy (n = 4), and others. Pneumonia, subphrenic abscess, and urosepsis occurred at a significantly higher frequency in elderly patients than in young patients. Our data clearly indicated that (1) the mechanism of injury, grade of associated intraabdominal injuries, distribution of surgical procedures, and complications differ significantly between young and elderly patients; and (2) the survival rate (65.5%) in elderly patients may be sufficient to consider anatomic hepatic resection to be a useful, safe procedure.

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-␣ in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-␣ neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-␣ stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P < .01); (2) membrane translocation (P < .05) and phosphorylation (P < .05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P < .01) and activity (P < .01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P < .001). Neutralizing anti-TNF-␣ antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-␣ stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-␣ stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway. (HEPATOLOGY 2002;35: 393-402.) P ortal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. Gastric hemorrhage-either spontaneous or caused by noxious agents such as alcohol and nonsteroidal anti-inflammatory drugs-occurs in ϳ30% of patients with PHT gastropathy. 1-3 Clinical and experimental data including our own indicate that compared with normal gastric mucosa, the PHT gastric mucosa has increased susceptibility to injury. 1,3-5 The microvascular abnormalities have been implicated in the increased susceptibility of PHT gastric mucosa to damage. [4][5][6][7][8] Excessive production of nitric oxide (NO) by endothelial NO synthase (eNOS) has been suggested as the basis for the systemic hyperdynamic and abnormal circulation of PHT gastric mucosa. [9][10][11][12] Tumor necrosis factor ␣ (TNF-␣) has been shown indirectly to be a major contributor to the hyperdynamic circulation likely through activation of NO synthase. [13][14][15] However, direct evidence for this has been lacking. Our previous study showed that elevated TNF-␣ up-regulates eNOS expression and its enzymatic activity in PHT gastric mucosa and that neutralization of TNF-␣ reverses the hemodynamic abnormalities of PHT gastric mucosa. 13 Although these data clearly indicate that TNF-␣ is involved in the activation of eNOS in PHT gastric mucosa, the molecular mechanisms and signaling pathways of eNOS a...