Yuichi Morishima

Effects of Soybean Oil Emulsion and Eicosapentaenoic Acid on Stress Response and Immune Function After a Severely Stressful Operation

OBJECTIVE To investigate the effects of soybean oil emulsion and oral or enteral administration of eicosapentaenoic acid (EPA) on stress response, cytokine production, protein metabolism, and immune function after surgery for esophageal cancer. SUMMARY BACKGROUND DATA It has been reported that safflower oil, rich in n-6 polyunsaturated fatty acid (n-6 PUFA), affects the survival rate of septic animals and decreases the immune function. It has also been reported that the administration of fish oil, in contrast, reduces these stress responses and stress-induced immunosuppression. In humans, the effects of soybean oil emulsion and the administration of EPA on stress response and immune function after surgery have not been established. METHODS Patients who underwent esophagectomy with thoracotomy were divided into three groups. Seven patients were fed by total parenteral nutrition (TPN) with soybean oil emulsion, which accounted for 20% of total calories. Seven patients were given oral or enteral administration of 1.8 g/day EPA, in addition to TPN with soybean oil emulsion. Nine patients served as the control group; these patients received fat-free TPN. Serum interleukin-6 (IL-6), C-reactive protein, concanavalin A (con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, natural killer cell activity, and stress hormones were measured. RESULTS The postoperative level of serum IL-6 was significantly higher in the group receiving soybean oil emulsion than in the fat-free group. Oral or enteral supplementation of EPA with soybean oil emulsion significantly reduced the level of serum IL-6 compared with the patients receiving soybean oil emulsion. Con A- or PHA-stimulated lymphocyte proliferation decreased significantly on postoperative day 7 in all groups of patients. The supplementation of EPA with soybean oil emulsion significantly improved the lymphocyte proliferation and natural killer cell activity on postoperative day 21 compared with the group receiving soybean oil emulsion. CONCLUSIONS Soybean oil emulsion amplifies, and the supplementation of EPA reduces, the stress response and stress-induced immunosuppression.

Effect of severity of stress on whole-body protein kinetics in surgical patients receiving parenteral nutrition

A study was conducted to clarify the quantitative relationship between the alteration of protein metabolism and the severity of surgical stress to further understand the mechanisms of body nitrogen losses in surgical trauma. Twenty-one patients undergoing esophagectomy for esophageal cancer (group E), and 22 undergoing gastrectomy or colorectal operations for gastric or colorectal cancer (Group GC) were studied. All patients were fed exclusively by parenteral nutrition (PN) providing 1.5 g protein.kg-1.d-1 and 35 kcal.kg-1.d-1 before and after the operation. The measurements of whole-body protein turnover, synthesis, and breakdown were performed preoperatively and on postoperative days (PODs) .3 and 10. Urinary excretion of total nitrogen and total catecholamines was also measured. Urinary excretion of the total catecholamines of group E was twice as high as that of group GC on the POD 3 and well reflected the severity of surgical stress. Negative correlation of nitrogen retention to urinary excretion of the total catecholamines was also observed (r = 0.64; P < 0.01). The correlations between the urinary excretion of the total catecholamines and the whole-body protein flux, synthesis, and breakdown were statistically significant (r = 0.57, 0.27, and 0.57, respectively; P < 0.01 in all). Rate of elevation in breakdown according to the stress level was greater than that of synthesis. Consequently the progressive aggravation of nitrogen balance according to the severity of surgical stress was observed.

Effect of intravenous ω-6 and ω-3 fat emulsions on nitrogen retention and protein kinetics in burned rats

Abstract The effect of ω-3 fat emulsion on nitrogen retention and kinetics in relation to fatty acid profile were investigated in burned rats receiving total parenteral nutrition (TPN). A fat emulsion of a structured symmetrical triacylglycerol containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2:1) was prepared. Sprague-Dawley rats were fed by fat-free chow for 2 wk. Then rats were fed exclusively with one of three types of TPN for 7 d. Animals in group C received fat-free TPN ( n = 11). Group ω6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake ( n = 11). Group ω3 received fat emulsion containing only EPA and DHA (1% of total calories, n = 11), in addition to safflower oil emulsion (19% of total calories). On day 5, each rat was subjected to 20% full-thickness scald burns. Rats were sacrificed under ether anesthesia 48 h after burning. The rats in group C became deficient in ω-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group ω6. The rates of whole-body protein synthesis were increased significantly in both groups ω6 and ω3. In ω6, however, the rates of whole-body protein breakdown were increased significantly. In conclusion, the rates of whole-body protein breakdown increased and nitrogen retention was aggravated significantly in animals administered the safflower oil emulsion. Significant increases of urinary excretion of total catecholamine were also observed. Prostaglandin E 2 and thromboxane B 2 concentrations were not significantly different among three groups. Supplementation with the new ω-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN.

Preoperative immunosuppression: its relationship with high morbidity and mortality in patients receiving thoracic esophagectomy

The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph node dissection, is a particularly stressful surgery that is characterized by high morbidity and mortality. The aim of this study was to evaluate the immunologic and nutritional states of patients to determine possible predictive factors of morbidity and mortality in patients receiving thoracic esophagectomy. Patients receiving thoracic esophagectomy were retrospectively divided into two groups. One group had postoperative infectious complications (group C+, n = 27), and the other had no complications (group C-, n = 76). They were treated with total parenteral nutrition or enteral nutrition providing 35-40 kcal. kg(-1). d(-1) of energy and 1.3-1.5 kcal. kg(-1). d(-1) of amino acids throughout the study period. The phytohemagglutinin (PHA)- and concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) from the patients were measured before and at days 7 and 21 after the operation. Serum albumin, prealbumin, transferrin, the retinol binding protein, and the C-reactive protein were also evaluated. Three patients out of 27 in group C+ died because of severe infectious complications, whereas none of patients was fatal in group C-. PHA- and Con A-induced proliferation of PBMC was significantly low before the operation and remained suppressed on the 21st postoperative day in group C+. No significant difference was observed in nutritional status during the perioperative days between the two groups. Our results indicate that esophageal cancer patients with preoperative suppression of the cell-mediated immunity can be identified as a higher risk population in the postoperative period. When adequate nutrition is received, however, the correlation between nutritional status and mortality disappears.

Increased contribution by myofibrillar protein to whole-body protein breakdown according to severity of surgical stress

A study was conducted to clarify the contribution by myofibrillar protein to whole-body protein breakdown in surgically stressed patients. Thirteen patients who underwent esophagectomy (group E) and 22 who underwent gastric or colorectal operation (group GC) were studied. Patients were all male and younger than 65 y old. Whole-body protein breakdown was determined using constant infusion of 15N-glycine. Urinary excretion of total catecholamines and 3-methylhistidine (3-MH) were measured. Amino acid composition of femoral arterial and venous blood was also analyzed. All the patients were fed exclusively by total parenteral nutrition providing 1.5 g protein and 40 kcal.kg-1.d-1 throughout the study. Whole-body protein breakdown increased significantly in group E (P < 0.01) and group GC (P < 0.05) on the 3rd postoperative day. The increase was significantly greater in group E than group GC (P < 0.01). Urinary excretion of 3-MH also increased significantly in group E (P < 0.01) and in group GC (P < 0.01) on the 3rd postoperative day. The increase was also greater in group E than group GC (P < 0.01). The ratio of urinary 3-MH excretion to whole-body breakdown protein (mumol/g), which is a indicator for the contribution of myofibrillar protein to the whole-body protein breakdown, increased significantly from 0.84 +/- 0.30 of preoperative value to 1.79 +/- 0.38 in group E (mean +/- SD; P < 0.01) and 1.42 +/- 0.18 in group GC (P < 0.05) on the 3rd postoperative day. This ratio was significantly higher in group E (P < 0.05). Furthermore, the ratio of myofibrillar to whole-body protein breakdown correlated significantly with urinary excretion of total catecholamines (r = 0.546; P < 0.01). Therefore, the contribution of myofibrillar protein to whole-body protein breakdown increased proportionately with the severity of surgical stress. On the other hand, femoral-arteriovenous differences of BCAA, Ala, Gln, Tyr, and Phe correlated significantly with the urinary excretion of 3-MH. These data suggest that skeletal muscle protein degradation is proportional to the breakdown of total myofibrillar proteins and both correlate with the severity of stress. From these data, it may be suggested that the contribution of skeletal muscle to whole-body protein catabolism is increased postoperatively, and that the increase is correlated with the severity of surgical stress.

Catabolism of lipoprotein-X induced by infusion of 10% fat emulsion

The clinical significance of lipoprotein-X (Lp-X) induced by intravenous infusion of 10% fat emulsion was assessed, with special reference to atherogenesis, by in vitro experiment using purified Lp-X from the sera of patients receiving Intralipid 10%. Lp-X appeared after long-term intravenous infusion of 10% fat emulsion in the patients with intestinal fistula due to the anastomotic leakage. To clarify the role of Lp-X in terms of atherogenicity, the cholesterol metabolism of Lp-X in macrophages as scavenger cells and in hepatocytes as parenchymal cells was studied. When [3H]cholesterol-labeled Lp-X or oxidized low-density lipoprotein (o-LDL) was incubated with J-774 macrophages, the incorporation of Lp-X into macrophages was negligible compared with o-LDL. When Lp-X or high-density lipoprotein (HDL) was incubated with J-774 macrophages laden with [3H]cholesterol, the release of cholesterol from macrophages was enhanced by Lp-X as well as HDL. When [3H]cholesterol-labeled Lp-X LDL or HDL was incubated with the human hepatoma cell line of Hep G2 cells, the incorporation of Lp-X into Hep G2 cells was less than that of LDL, but similar to that of HDL. From these findings, it is suggested that the catabolism of Lp-X cholesterol generated with intravenous 10% fat emulsion was mediated by hepatocytes rather than by macrophages, indicating that the hyperlipidemia due to increased Lp-X may not be atherogenic.

Effects of insulin-like growth factor-1 on endotoxin translocation in burned rats receiving total parenteral nutrition.

The purpose of this study was to investigate the effect of insulin-like growth factor-1 (IGF-1) on the translocation of endotoxin from the gut of burned rats. Twenty-eight male Sprague-Dawley rats (7-wk-old) were subjected to 20% full-thickness scald burns and were divided into two groups. One group received 4 mg.kg-1.d-1 of IGF-1 (IGF-1 group, n = 14), and the other received saline (control group, n = 13). All rats were fed exclusively by total parenteral nutrition (TPN). On the second postburn day, rats were killed. The amount of endotoxin in the liver and spleen were measured. RNA from the terminal ileum was extracted, and Northern blot analyses of alpha-tubulin, beta-actin, cell division cycle-2 (cdc2), and immunoglobulin-A (IgA) were performed. Nitrogen balance was improved (p < 0.001), and the wet weight of intestine and its mucosa were increased significantly in the burned rats that received IGF-1. Gene expression of alpha-tubulin and beta-actin were not changed. Cdc2 was elevated (P < 0.05), but IgA was decreased (P < 0.05) in the IGF-1 group. Levels of endotoxin in the liver and spleen were significantly reduced (P<0.05) by the administration of IGF-1. A negative correlation between the levels of endotoxin in the liver and the weight of the intestinal mucosa was observed. In conclusion, IGF-1 improved nitrogen balance, promoted the proliferation of intestinal mucosa and reduced the translocation of endotoxin.

Successful esophageal bypass operation for esophagobronchial fistula following chemotherapy for malignant lymphoma: a case report

A 72-year-old man with non-Hodgkin’s lymphoma at the tracheal bifurcation node received combination chemotherapy and subsequently developed a fistula in spite of remission of the lymphoma. Conservative therapy did not heal the fistula formation, and we chose bypass surgery using a gastric tube without thoracotomy. Ten months postoperatively, there is no evidence of lymphoma relapse and the patient lives a normal life. We consider this procedure as an available treatment for esophagobronchial fistula in case of failure to cure fistula communication by conservative therapy.

An inflammatory fibroid polyp of the esophagus concomitant with a superficial flat carcinoma

Abstract We report a rare case of an inflammatory fibroid polyp (IFP) of the esophagus associated with an extensive early mucosal carcinoma. At esophagoscopy, a polypoid lesion 2 cm in length, and a non-stained area detected by the Lugol iodine spray staining method were found in the mid-thoracic portion, and esophagectomy was performed. Endoscopic polypectomy is thought to be useful for the diagnosis of IFP, but it should be kept in mind that IFP may be concomitant with carcinoma. Indeed, in our patient, early esophageal carcinoma was discovered because of the symptoms of dysphagia induced by the IFP.