Keiji Iriyama

Apolipoprotein C-II Modifications Associated with an Infusion of Artificial Lipid Particles

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.

Hepatic Infarction as a Complication of Gastric Cancer Surgery: Report of Four Cases

Four cases of patients who developed hepatic infarction caused by an operative injury to the hepatic circulation during gastric cancer surgery are reported herein. In two patients, the hepatic infarction resulted from accidental injury to the proper hepatic artery, and in the other two, it was possibly due to persistent pressure on the folded liver by a retractor during surgery. In the former two patients, the proper hepatic artery had been collapsed by the spread of enlarged metastatic lymph nodes before the onset of the arterial injury. In the latter two patients, postoperative laboratory data and computed tomography scanning revealed hepatic infarction even though preservation of the proper hepatic artery was confirmed by angiography. Elevated serum levels of hepatic enzymes released from the infarcted tissue recovered to the normal range within three weeks in all four patients. In conclusion, when an operative injury to the hepatic artery is encountered, the hepatoduodenal ligament should not be manipulated any more than necessary to preserve the collaterals, and the gallbladder should be removed to prevent necrotic perforation. Although close observation is mandatory, conservative therapy seems to be sufficient when an infarcted area is restricted to the lateral segment and a small part of the medial segment of the liver.

Clinical significance of serum hepatocyte growth factor in orthotopic liver transplantation

BACKGROUND Hepatocyte growth factor (HGF) plays a key role in the regulation of liver regeneration after hepatocyte damage. Changes in HGF production reflect the status of the regeneration process. METHODS Serum concentrations of HGF and energy substrates were measured during and after liver transplantation in 30 recipients. RESULTS In the patients with compromised grafts (group A) HGF concentrations were persistently high after reperfusion, whereas in the patients with well-functioning grafts (group B), HGF concentrations decreased rapidly and remained low 4 hours after reperfusion. The patients in group A who died had persistently high concentrations of HGF. The surviving patients with reversible primary graft dysfunction in group A exhibited low concentrations 48 hours after reperfusion. The decrease in HGF concentration preceded the decrease in aspartate aminotransferase concentration. The metabolic parameters that reflect carbohydrate metabolism by the graft paralleled the changes in HGF. CONCLUSIONS HGF may be more sensitive and specific in predicting early graft function than prothrombin time, ratio, aspartate aminotransferase, or arterial ketone body ratio. The determination of HGF levels after liver transplantation may yield valuable information for evaluating early graft function and making an early decision to repeat a graft procedure in an acutely ill patient.

Serum Cell Adhesion Molecules in Patients with Colorectal Cancer

The serum levels of intercellular adhesion molecule-1 (sICAM-1) and endothelial leukocyte adhesion molecule-1 (sELAM-1) were determined in 40 patients with colorectal cancer. The sICAM-1 and sELAM-1 levels in the drainage venous blood adjacent to a tumor were significantly correlated with those in the peripheral venous blood in patients without evident hematogenous dissemination of tumor cells. The sICAM-1 levels in peripheral venous blood were significantly higher in patients with hepatic metastases, while the sELAM-1 levels were significantly higher in those with pulmonary metastases. An immunohistochemical study of metastatic sites in the liver revealed that ICAM-1 was expressed in cancer stroma, but not in the cancer cells. In conclusion, the sICAM-1 and sELAM-1 levels in the peripheral venous blood in colorectal cancer patients without any distant metastasis are likely to reflect the topical production of these cell adhesion molecules, and appear to be instructive in predicting hematogenous dissemination in patients with colorectal cancer.

Nonoperative treatment for a ruptured pseudoaneurysm of the celiac trunk: Report of a case

We report the case of a 67-year-old man in whom hemorrhage from a ruptured celiac trunk pseudoaneurysm, which occurred as a consequence of leakage at the site of gastroduodenostomy, was successfully controlled by transcatheter arterial embolization (TAE) with stainless steel coils and N-butyl cyanoacrylate (NBCA). The occurrence of a pseudoaneurysm of the celiac trunk associated with anastomotic leakage is etiologically rare. We compiled reports from the literature on TAE for ruptured aneurysms of the celiac trunk, and compared its therapeutic value with that of surgical treatment. Operative death occurred in 4 of a series of 43 patients with aneurysms of the celiac trunk that were surgically treated (9.3%). In 5 patients with ruptured aneurysms, the operative mortality rate was 40% (2/5). Conversely, while the unsuccessful rate of TAE therapy was 17% (1/6), the mortality rate was nil. The patient whose case is presented here was affected by methicillin-resistant staphylococcus aureus (MRSA) at the site of leakage and in the lung. Under septic conditions such as hemorrhage secondary to pancreatitis, the mortality rate of surgical therapy was 23%–29%, whereas the success rate of TAE therapy was 79% and the mortality rate was 4%. Based on these findings, it is suggested that TAE therapy is a viable alternative to surgery for patients even with ruptured pseudoaneurysms of the celiac trunk.

THE METABOLIC DISTINCTIVENESS OF EMULSIFIED LIPID PARTICLES IN THE BLOODSTREAM AND ITS CLINICAL IMPLICATIONS

The advantages of administering intravenous fat emulsions are well known. Primarily, they are important sources of essential fatty acids; they allow the administration of many calories within a small volume; and they are isotonic compared to body fluid. In this review, the metabolic distinctiveness of parenterally infused fat particles in the bloodstream is evaluated under four main headings: (1) the structure and metabolism of fat emulsion particles; (2) the metabolism of phospholipid-rich fat emulsion; (3) the interactions between fat emulsion particles and plasma lipoproteins; and (4) the acquisition of protein moieties (apolipoproteins) by fat emulsion particles and its clinical implications.

Elimination rate of fat emulsion particles from plasma in Japanese subjects as determined by a triglyceride clamp technique

The elimination rate of emulsion triglyceride (TG) from plasma was investigated in Japanese subjects by a plasma TG clamp technique. Two different studies were performed. In Study 1, a lipid emulsion (20% long-chain triglyceride emulsion: LCT) was infused into a healthy research associate to achieve a certain concentration of TG in the plasma. Thereafter, the infusion rate was adjusted to maintain the chosen concentrations of TG in plasma (namely, 4-5 mmol/L, 3-4 mmol/L, and approximately 2 mmol/L) over a period of 160 min by measuring plasma TG concentrations at 10-min intervals. Concentrations of TG in plasma were clamped within 2.13 +/- 0.13 mmol/L by an infusion rate of 0.10 g.kg-1.h-1, within 3.34 +/- 0.20 mmol/L by an infusion rate of 0.14 g.kg-1.h-1, and within 4.46 +/- 0.22 mmol/L by an infusion rate of 0.11 g.kg-1.h-1. The mean rate of infusion of emulsified TG that had maintained the steady concentrations of TG in plasma was limited to the very narrow range of 0.12 +/- 0.02 g of TG.kg-1.h-1 regardless of the chosen concentration of TG in plasma. Concentrations of nonesterified fatty acids (NEFA) also remained at a fixed level of 1.378 +/- 0.103 mEq/L regardless of the chosen concentration of TG in the plasma. Study 2 was undertaken to determine whether plasma TG concentration reached a plateau during a period when emulsion TG was infused into three different subjects at a rate of 0.12 g.kg-1.h-1. The plasma TG concentrations were steady at a level of 2.04 +/- 0.32 mmol/L, and the plasma NEFA concentrations remained at a fixed level of 1.33 +/- 0.13 mEq/L, over a period of 160 min after 50-min priming infusion. These results indicate that the plasma TG elimination rate was limited to the narrow range of 0.12 +/- 0.02 g.kg-1.h-1 when the fat emulsion was infused into Japanese subjects in a steady state. However, the plasma TG elimination rate in Japanese subjects appeared to be lower than that of Europeans. This may be due to a difference in lipoprotein lipase activity caused by different dietary habits, namely, a lower fat intake.

Influences of an Infusion of Lipid Emulsion on Phagocytotic Activity of Cultured Kupffer's Cells in Septic Rats:

An experimental study was undertaken to study the influences of an infusion of lipid emulsion on phagocytosis of Kupffers cells in septic rats. Sepsis was induced in 13 rats by ligating the cecum. Five of them received glucose as the sole nonprotein calorie (septic-glucose group), four of the rats received 25% of the nonprotein calorie with lipid emulsion, Intralipid (septic-lipid group), and the remaining four rats did not receive any intravenous solution and were allowed access to water (septic-fasted group). Another four rats which received neither intravenous solution nor ligation of the cecum served as the control group. The intravenous infusion was carried out for 72 hr. The phagocytotic activity of Kupffers cells was determined by the ability to engulf latex particles with a size of 1.09 micron, in vitro. The phagocytotic activity was enhanced by the presence of sepsis but it was inhibited by starvation. The difference in the phagocytotic activity between the septic-glucose group and the septic-lipid group was not significant. These results suggest that, insofar as an in vitro study is concerned, a 72-hr infusion of lipid emulsion at a rate of 25% of the total nonprotein calorie does not influence the phagocytotic activity of cultured Kupffers cell obtained from septic rats.

Constant infusion rates of lipid emulsions to stabilize plasma triglyceride concentrations: medium-chain triglyceride/long-chain triglyceride emulsions (MCT/LCT) versus LCT.

As medium-chain triglyceride emulsions (MCT) are more rapidly hydrolyzed than long-chain triglyceride emulsions (LCT), MCT/LCT tends to be infused faster than LCT. The purpose of the present study was to determine the most appropriate infusion rate for MCT/LCT to stabilize plasma concentrations of triglyceride (TG), being equivalent to the optimal infusion rate of the emulsion. A TG clamp was set up by raising the mean ± SD concentrations of TG in plasma, being 1.08 ± 0.18Δ mmoll−1 for LCT, and 1.65 ± 0.31 Δ mmoll−1 for MCT/LCT after a 50-min priming infusion of each emulsion. Thereafter, the infusion rate of lipid was controlled every 10 min to maintain a steady concentration of TG for a period of 150 min. A constant infusion of glucose at 0.32 g/kg body weight (BW) per h was administered for the test period. The weight-based rate of the infusion to maintain a steady state of plasma TG concentrations did not differ between MCT/LCT and LCT, being 0.125 ± 0.013vs 0.117 ± 0.021 g/kg BW per h, while the molar-based infusion rate was 0.203 ± 0.021 mmol/kg BW per h for MCT/LCT and 0.132 ± 0.023 mmol/kg BW per h for LCT (P < 0.05). These results suggest that although 54% more molar MCT/LCT-TG can be hydrolyzed during a constant infusion, MCT/LCT should not be infused at a rate faster than 0.1 g/kg BW per h under a steady state.

Colorectal Cancer in a Patient Younger than 20 Years of Age : Report of a Case and a Review of the Japanese Literature

This article presents a case of advanced cancer of the transverse colon seen in an 18-year-old woman who underwent a potentially curative resection. The histological type of cancer was well-differentiated adenocarcinoma. After reviewing the clinicopathological features of 110 colorectal cancer cases in patients younger than 20 years of age compiled from the Japanese literature, the high incidence of poorly differentiated carcinoma (51.5% for poorly differentiated adeno-carcinoma, signet-ring cell carcinoma, mucinous carcinoma, and undifferentiated carcinoma) and of more advanced stages (67.1% for clinical stages IIIb and IV) were found to be characteristic for patients with colorectal cancer younger than 20 years of age. The presence of more advanced disease and the high incidence of poorly differentiated carcinoma thus seem to be related to the low postoperative survival rates. The 2-year survival rate was 19.8% and the 5-year survival rate was 8.8% in colorectal cancer patients younger than 20 years of age.