Masaru Uchinami

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.

A New Surgical Approach for Resection of Cancer of Gastric Cardia

Thirty-five consecutive patients with adenocarcinoma of the gastric cardia were operated with a new technique which involved wide resection of the peri-hiatal diaphragm, dissection of the upper abdominal and lower mediastinal lymph nodes, and resection of the stomach including a portion of the lower esophagus without thoracotomy. The mediastinal node stations were affected in 25% of patients, whose tumor invaded to the serosa. Hhypotension with or without atrial arrythmias and pleural tears occurred during surgery in 20 patients (57%), and in 18 (51%), respectively. Postoperatively, hypoxia requiring reintubation developed in 7 patients (19%), pleural effusions needed tube drainage in 16 (46%), atelectasis in 5 (14%) and anastomotic leaks in 3 (9%). The cumulative 5 year survival rate for 21 patients was 62%, whereas none of the patients with stage IV disease lived for more than 2 years after surgery. We believe this technique is a reasonable and safe alternative to the left thoracotomy approach for resection of cancer of the gastric cardia.

A Novel Method for Restoration of Postoperative Defecation Function in the Patients with the Lower Rectal Cancer

A new attempt with purpose of preserving the anal canal as much as possible was conducted in the patients with distal rectal cancer in which the anal canal would be resected when a usual sphincter sparing operation is applied. The novel point about this technique is that the everted anal canal in the perineum at the time of the invaginated technique of the Maunsell-Weir method is resected diagonally to permit the preservation of the maximum length of the anal canal. Indications for this procedure included the low region at a distance less than 4 cm from the dentate line, less than T2 for mural stage, and less than 1/3 the circumference for size. Four patients on which this technique was sequentially performed since 3 years ago were favarably reviewed from the various aspects such as tumor size, site, mural stage, lymph node metastasis, postoperative urination/defecation function, and stool soilage. We believe that this method should be the operation of choice in selected patients with low rectal cancer.

Invagination method with diagonal resection of the anal canal for cancer of the lower rectum

If the length of the remaining anal canal after surgery is not adequate, various problems with defecation can occur. With the purpose of preserving the anal canal as much as possible, a new attempt was made in patients with distal rectal cancer in whom the anal canal would be resected when the usual sphincter-sparing operation is applied. The novelty of this technique is that, when the invaginated technique of the Maunsell-Weir method is performed, the everted anal canal in the perineum is resected diagonally to permit preservation of a maximum length of the anal canal. Anastomoses with the diagonal rectal stump prohibit strictures, which frequently occur upon colo-anal anastomosis. Indications for this procedure include: the low region, at a distance less than 4 cm from the dentate line; less than T2 for mural stage, and less than one third the circumference for size. Four patients, in whom this technique was sequentially performed 3 years ago, were favorably reviewed according to various aspects such as tumor size, site, mural stage, lymph node metastasis, postoperative urination/defecation function, and stool soilage. We believe that this method should be the operation of choice in selected patients with low rectal cancer.