Involvement of the neuropeptide substance P in lung inflammation induced by hepatic ischemia/reperfusion.

OBJECTIVE AND DESIGN: The purpose of this study was to examine the potential role of substance P in accumulation of neutrophils in the lung following hepatic ischemia/reperfusion. MATERIALS AND METHODS: Male C57BL/6 mice (8-10 weeks of age) were subjected to either sham surgery, partial hepatic ischemia with or without reperfusion, or intratracheal administration of saline or 1 ng substance P. Lung neutrophil accumulation was assessed by tissue content of myeloperoxidase. Activation of the transcription factor, NF-kappaB, was determined by electrophoretic mobility shift assay. Levels of substance P and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage (BAL) fluid was measured using enzyme-linked immunosorbent assays. RESULTS: Significant pulmonary neutrophil accumulation was observed just prior to hepatic reperfusion in association with increased BAL levels of substance P. Intratracheal administration of substance P resulted in a similar pattern of neutrophil accumulation which was associated with activation of NF-kappaB and increased BAL levels of the chemokine, MIP-2. CONCLUSIONS: The data suggest that hepatic ischemia causes substance P release in the lung which activates NF-kappaB leading to the production of MIP-2 and accumulation of neutrophils.

Unilateral hepatic artery reconstruction is unnecessary in biliary tract carcinomas involving lobar hepatic artery: implications of interlobar hepatic artery and its preservation.

BACKGROUND/AIMS: The interruption of hepatic arterial flow when performing a bilioenteric anastomosis has been reported to usually bring about serious postoperative complications, such as anastomotic leakage, hepatic abscess and infarction. We aimed to evaluate the surgical implications of the interlobar hepatic artery when patients with advanced biliary tract carcinomas undergo surgical resection with a bilioenteric anastomosis. METHODOLOGY: In 7 patients with advanced biliary tract carcinomas, the combined resection of the liver (greater than hemihepatectomy in 2 and less than hemihepatectomy in 5), extrahepatic bile duct, hepatic artery (right hepatic artery in 5, right and left hepatic artery in 1, left hepatic artery in 1), and the portal vein was performed in 4 patients. The portal vein was reconstructed in all 4 patients. The hepatic artery was reconstructed in only one patient, with combined resection of both right and left hepatic arteries, but was not reconstructed in 2 other patients, even though they underwent resection greater than hemihepatectomy. RESULTS: The interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence could be preserved in 5 patients, as shown by angiography, but could not be preserved in 2 patients who underwent greater than hemihepatectomy. Moderate and transient ischemic liver damage occurred, but no serious postoperative complications were induced in any of the 5 patients in the unilateral hepatic artery preserved group. However, both cases without preservation of the hepatic artery encountered liver failure, liver abscess and leakage of bilioenteric anastomosis, and one patient died of multiple organ failure. CONCLUSIONS: One major lobar branch of the hepatic artery involved by cancer invasion could be safely resected without reconstruction in patients with advanced biliary tract carcinomas when the interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence is preserved.

Parenchyma-preserving hepatectomy in the surgical treatment of hilar cholangiocarcinoma.

BACKGROUND: Although extended hepatic resection has been shown to improve prognosis by increasing the surgical curability rate in hilar cholangiocarcinoma, high surgical morbidity and mortality rates have been reported in patients with obstructive jaundice. Postoperative liver failure after hepatic resection in patients with obstructive jaundice has been shown to depend on the volume of the resected hepatic mass. The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy in a surgical treatment for hilar cholangiocarcinoma. STUDY DESIGN: Ninety-three resected patients with hilar cholangiocarcinoma were included in this retrospective study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66), the parenchyma-preserving hepatectomy (PPH) group (n = 14), and the local resection (LR) group (n = 13). The EXH group had undergone hepatectomy more extensive than hemihepatectomy, the PPH group had undergone hepatectomy less extensive than hemihepatectomy, and the LR group had undergone extrahepatic bile duct resection without hepatic resection. Surgical curability, defined by histologically confirmed negative surgical margins, surgical morbidity and mortality, and survival rates were compared among the three groups. The clinicopathologic factors were studied for prognostic value by univariate and multivariate analyses. RESULTS: Surgical curability of the PPH and EXH groups was better than that of the LR group. Fifty-four percent of patients in the LR group showed positive surgical margins at the hepatic stump of the bile duct, compared with 7% in the PPH group and 20% in the EXH groups (p < 0.01 for each comparison). Surgical morbidity was higher in the EXH group (48%) than in the LR group (8%) and the PPH group (14%) (p < 0.01 and p < 0.05, respectively). Postoperative hyperbilirubinemia occurred more frequently in the EXH group (29%) than in the LR and PPH groups (0% and 0%, respectively, p < 0.05 for each comparison). Survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR, 29% versus 8% at 5 years, respectively (p < 0.05). But no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analyses showed that significant prognostic factors for survival were resected margin, lymph nodal status, and vascular resection. CONCLUSIONS: In conclusion, PPH could obtain a curative resection and improve the outcomes for patients with hilar cholangiocarcinoma that is localized at the hepatic duct confluence who do not require vascular resection. PPH might bring about a beneficial effect in highly selected patients according to extent of cancer and high-risk patients with liver dysfunction.