Yasuyoshi Toyoda

Modulating Effects of the Feeding Route on Stress Response and Endotoxin Translocation in Severely Stressed Patients Receiving Thoracic Esophagectomy

Experimental studies have demonstrated that the route of nutritional supply impacts the systemic metabolic responses after surgical injury. Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) or prolonged bowel rest, has been reported to enhance bowel endotoxin translocation. The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph-node dissection, is a particularly stressful surgery that requires long-term aggressive nutritional support and often results in the postoperative hypermetabolic state, leading to perturbation of postoperative immune function. Interleukin-6 (IL-6) plays an important role in host inflammatory responses, whereas IL-10 is linked to suppression of cellular immunity. The aim of this study was to investigate how the antecedent nutritional routes influence systemic IL-6 and IL-10 responses and endotoxin translocation after an operation for thoracic esophageal cancer. Twenty-nine patients who underwent esophagectomy with three-field lymphadenectomy were investigated. They were assigned to groups receiving either TPN (n = 18) or enteral nutrition (EN; n = 11) providing 35 kcal x kg(-1) x d(-1) of energy and approximately 1.2-1.5 g x kg(-1) x d(-1) of amino acids. These nutritional supports were conducted from 1 wk before the operation to 14 d after the operation. Serum IL-6, IL-10, and endotoxin concentration were measured before and during the operation and at 2 h and 1, 3, and 7 d after the operation. IL-6 in sera was significantly higher after the operation in both groups. In the EN group, however, significantly less IL-6 production was observed on the third and seventh postoperative days when compared with those patients in the TPN group. Similarly, serum IL-10 concentration in the TPN group showed a significantly higher level than that in the EN group. Serum IL-6 showed a significant positive correlation with IL-10 at 2 h and at 7 d after the operation, suggesting that the reduced inflammatory responses were related to the inhibition of the development of postoperative immunosuppression. Endotoxin concentration in sera was significantly lower in the EN group after the operation than in the TPN group. Perioperative EN provides better regulation of inflammatory cytokine responses and may contribute less to immunosuppression after major surgery than parenteral nutrition. The attenuated production of endotoxin induced by EN may play an important role in these phenomena.

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.

Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.

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.

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.