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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...

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In the 1990s, laparoscopic surgery entirely changed the traditional style of surgical operations. Laparoscopic cholecystectomy has spread rapidly and is now established as the standard treatment. However, besides cholecystectomy, endoscopic procedures are still not applied so widely to a variety of surgical operations. This is because laparoscopic techniques, such as suturing or ligation, make it difficult for surgeons to perform other kinds of operations and thus greatly increase their mental and physical stress. It is necessary to introduce various advanced technologies such as: surgical robots, three dimensional (3D) images, computer graphics (CG), computer simulation technology and others. Surgical robots, including the AESOP, da Vinci and ZEUS systems, provide surgeons with technologically advanced vision and hand skills. As a result, such systems are expected to revolutionize the field of surgery. However, there have so far been few studies which discuss the indications of robotic surgery for tumors/cancer. Therefore, herein we review various studies published in English to focus on the application of robotic surgery to tumors/cancer. We point out that there are several problems to be solved for robot surgery: i) price of surgical robots, ii) training systems for surgeon, iii) coverage by medical insurance, iv) downsizing and v) navigation system. In conclusion, we believe that, in the near future as robotic technology continues to develop, almost all kinds of endoscopic surgery will be performed by this technology. It will replace traditional surgery not only in the treatment of benign diseases but also in malignant illnesses.

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa. (HEPATOLOGY 2001;34:990-999.)Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis, the fourth leading cause of death in Americans between the ages of 35 to 54. Approximately 30% of the patients afflicted with PHT gastropathy develop life-threatening gastric hemorrhage, either spontaneously or caused by noxious agents such as alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs). [1][2][3] Clinical and experimental data indicate that, compared with normal gastric mucosa, the PHT gastric mucosa is highly susceptible to injury. [4][5][6] The ultrastructural abnormalities of PHT gastric mucosal microvessels and submucosal blood-flow shunting, producing mucosal surface hypoxia, have been implicated in the increased susceptibility of PHT mucosa to damage. [7][8][9] Other, probably related, factors such as excessive NO production and increased generation of oxygen free radicals and lipid peroxidation in PHT gastric mucosa have also been implicated in its increased susceptibility to injury. [10][11][12] Lacking, however, is a clear understanding of the molecular basis for this phenomenon. Although seemingly contradictory, oxidative stress has been shown to be induced by hypoxia contributing to pulmonary hypertension 53 and in the liver through a mechanism involving peroxynitrite formation. 54 Mitogen-activated protein (MAP) kinases play pivotal roles in regulating cellular responses to growth factors and to oxidative stress. [13][14][15][16] The extracellular signal-regulated kinases, ERK-1 and -2 (isoforms of MAPK), play key roles in initiating prolife...

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual-specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids. PTEN inhibits activation of Akt, the downstream effector of PI 3-kinase, which is integral to cell proliferation, migration, survival, and angiogenesis essential for tissue injury healing. PTEN expression and activation during injury healing remain unexplored. Portal hypertensive (PHT) gastric mucosa has impaired injury healing, but the underlying mechanisms remain unknown. We investigated whether impaired healing of injured PHT gastric mucosa is due to abnormal PTEN expression/activation that leads to decreased Akt activation. We also investigated the possible involvement of Egr-1, which regulates PTEN in some cells (e.g., fetal kidney epithelial cells), and TNF-alpha, which can induce Egr-1 expression. In PHT gastric mucosa 6 h after injury, PTEN protein levels were increased by 2.7-fold; unphosphorylated PTEN (reflecting activated PTEN) was increased by 2.4-fold; Akt phosphorylation (reflecting Akt activation) was reduced by 2-fold; and Egr-1 expression was increased by 3.3-fold vs. normal gastric mucosa. TNF-alpha neutralization reversed all of the above abnormalities in PHT gastric mucosa, reduced mucosal injury, and enhanced healing. We conclude that, in injured PHT gastric mucosa, overexpressed/activated PTEN leads to the reduced activation of the PI 3-kinase/Akt pathway that results in impaired injury healing.