Takanori Tabo

EFFECT OF INTERMITTENT HEPATIC PEDICLE CLAMPING ON FREE RADICAL GENERATION IN THE RAT LIVER

BACKGROUND Intermittent hepatic pedicle clamping is thought to cause less hepatic reperfusion injury compared with continuous clamping. The mechanisms underlying this difference are unknown. We examined the relationship between intermittent ischemia/reperfusion and the production of free radicals using electron spin resonance spectrometry. METHODS Alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone was administered to rats as a spin trap agent. Continuous clamping (15, 30, or 60 minutes) or intermittent clamping (four cycles of 15-minute ischemia and 5 or 15 minutes of reperfusion) of hepatic pedicle was carried out. After reperfusion, free radical production in the liver was measured by an electron spin resonance spectrometer, and the level of hepatic injury was evaluated by measuring liver enzyme. RESULTS Longer periods of ischemia increased free radical production after reperfusion. There was no significant increase in free radical production or liver enzymes when the duration of ischemia was 15 minutes. Free radical production and liver damage were significantly less severe in intermittent pedicle clamping than in continuous clamping for 60 minutes, especially when the duration of the reperfusion between four cycles of ischemia was 15 minutes. CONCLUSIONS These results indicate that intermittent pedicle clamping lessens free radical production when compared with continuous clamping, although many free radicals are produced.

Neutrophil Elastase Inhibitor Reduces Hepatic Metastases Induced by Ischaemia-Reperfusion in Rats

OBJECTIVE To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN Laboratory experimental study. SETTING Research laboratory, Japan. SUBJECTS Male Fischer rats. INTERVENTIONS Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.

Intermittent Hepatic Ischemia-Reperfusion Minimizes Liver Metastasis in Rats

BACKGROUND Surgical stresses, including hepatic ischemia-reperfusion (I/R), promote cancer growth and metastasis. We have reported that continuous hepatic I/R increases liver damage and promoted liver metastasis from colon cancer, whereas intermittent I/R causes less liver damage. We therefore examined whether intermittent I/R could reduce liver metastasis in a rat model. MATERIALS AND METHODS Adult male Fischer rats was divided between three groups: group A (control), which received laparotomy for 120 min with no liver ischemia; group B (continuous I/R), which received 60 min of 70% partial liver ischemia followed by 60 min of reperfusion; and group C (intermittent I/R), which received 15 min of 70% ischemia and 15 min of reperfusion, repeated four times. Just before closing the abdomen, all animals were inoculated intrasplenically with rat colon adenocarcinoma cells (RCN-H4). Tumor nodules on the liver surface were counted 3 weeks later. In addition, expression of E-selectin mRNA in liver was examined at 1, 3, and 6 h after completing I/R by a reverse transcription-polymerase chain reaction. RESULTS Continuous I/R (B) greatly promoted liver metastasis in both ischemic and nonischemic liver lobes, whereas intermittent I/R (C) showed significantly fewer metastasis than group B in both lobes. Significantly less E-selectin mRNA was expressed in group C than in group B. CONCLUSIONS Intermittent I/R limits expression of E-selectin mRNA and liver metastasis. Intermittent hepatic I/R is less stressful than continuous I/R, minimizing liver metastasis by colon cancer cells through avoidance of E-selectin up-regulation.

Ruptured Pseudoaneurysm Associated with Pancreatic Pseudocyst during the follow-up Period-Report of a Case and Review of the Literature-

症例は31歳の男性で, 平成9年頃からアルコール性膵炎の加療歴があり, 腹部CT検査では膵仮性嚢胞が指摘されていた. 平成12年2月3日に左上腹部痛のため入院. 腹部CT検査では, 膵尾部に直径約5cmの膵仮性嚢胞を認め, 嚢胞内脾門部寄りに造影効果のある径5mm大の腫瘤を認めた. 保存的治療により軽快したが, 3か月後に腹部CT検査を行ったところ, 膵仮性嚢胞の増大と嚢胞内に突出する脾仮性動脈瘤が疑われ, さらに嚢胞内への出血も疑われた. 5日後の腹部CT検査で動脈瘤の増大を認めたため, 血管撮影を行い, 脾仮性動脈瘤を確認した後, 同部の血管塞栓術を行った. 2週間後, 待期的に膵仮性嚢胞の根治術として動脈瘤を含めた膵体尾脾合併切除術を行い良好な結果を得ている.