P.L. Yap

Acute phase responses following minimal access and conventional thoracic surgery

OBJECTIVES Major thoracic surgery is associated with trauma-related immunological changes. These may impair anti-tumour immunity. We hypothesize that the reduced operative trauma associated with a video-assisted thoracic surgery (VATS) approach may decrease acute phase responses and, consequently, lead to better preservation of immune function. This prospective randomized study compared the effects of conventional open thoracic surgery and VATS on acute phase responses in patients undergoing pulmonary lobectomy. METHODS Acute phase indicators were analyzed in patients undergoing lobectomy for suspected bronchogenic carcinoma. Surgery was prospectively randomized to pulmonary lobectomy by VATS or limited postero-lateral thoracotomy. Blood was taken pre-operatively and at 4, 24, 48, 72, 120 and 168 h post-operatively for analysis of C-reactive protein (CRP; 41 patients: open, n=22; VATS, n=19) interleukin (IL)-6, tumour necrosis factor (TNF) receptors (TNF-sR55, TNF-sR75) and P-selectin (24 patients: open, n=12; VATS, n=12). Samples taken at 48 and 168 h were also analyzed for phagocyte reactive oxygen species (ROS) production (25 patients: open, n=16; VATS, n=19). RESULTS Surgery increased acute phase responses. VATS was associated with lower CRP and IL-6 levels. In the open surgery group, significant increases in ROS in neutrophils (up to 36% greater than before surgery, n=12, P<0.02-0.05) were detected at 2 days after surgery, but in the VATS group, the increase after surgery (of up to 17%, n=18) did not reach significance. Similarly, monocyte ROS increases of up to 25% in the mean ROS in the open surgery group and of up to 17% in the VATS group were detected on days 2 and 7 after surgery. CONCLUSIONS VATS pulmonary lobectomy is associated with reduced peri-operative changes in acute phase responses. This finding may have implications for peri-operative tumour immuno-surveillance in lung cancer patients.

Effect of blood transfusion on survival after esophagogastrectomy for carcinoma.

BACKGROUND There is growing evidence that blood transfusion is associated with clinical factors that can lead to transfusion-induced immunosuppression. This effect can be beneficial or deleterious. METHODS The effect of perioperative allogeneic blood transfusion on survival was studied retrospectively in 524 patients who were discharged from the hospital after esophagogastrectomy for carcinoma performed in a single unit over a 10-year period. RESULTS The median operative blood loss for the series was 500 mL (range, 50 to 3,750 mL). Three hundred thirty-five patients (64%) received a perioperative allogeneic blood transfusion related to esophagogastrectomy, and 189 (36%) did not. The median perioperative blood transfusion administered was 900 mL (range, 300 to 12,950 mL). Perioperative allogeneic blood transfusion was associated with reduced survival for patients in stage III (p < 0.05) at 1 year, but no significant difference was found in this stage at 3 or 5 years after resection. Stage III disease accounted for 250 (48%) of the 524 patients discharged. CONCLUSIONS Although perioperative allogeneic blood transfusion does not affect long-term survival after esophagogastrectomy for carcinoma, it does have a significant association with short-term survival in a group whose overall survival is often limited after resection. Attention should be directed toward minimizing operative blood loss and transfusing only for factors known to be clinically important, such as oxygen delivery and hemodynamics, not arbitrary hemoglobin levels.

Endotoxin releases platelet-activating factor from human monocytes in vitro

The role of platelet-activating factor (PAF) in human endotoxaemia was investigated by incubating human monocytes from 27 subjects with S. minnesota endotoxin in vitro. Monocytes synthesized 1.01 +/- 0.4 x 10(-10) M to 5.3 +/- 1.51 x 10(-9) M PAF after 60 min of incubation with endotoxin at concentrations of 1 x 10(-8) M and 4.5 x 10(-6) M respectively. The endotoxin-stimulated release of PAF was not significantly increased in monocytes cultured on a human endothelial cell monolayer. This rapid release of PAF in response to endotoxin is consistent with a role for monocyte-derived PAF as a toxic mediator of the acute systemic changes observed in patients with endotoxin-related septic shock.

Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality.

Abstract. Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflor‐escein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C‐reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leucocytes from patients who died was significantly higher (P<0.001) than paired controls, and greater (P<0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte‐derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.

Macrophage prostaglandin E2 and oxidative responses to endotoxin during immunosuppression associated with anaesthesia and transfusion

The widespread use of blood transfusion in major surgical procedures has led to concern about the immunosuppressive effect of transfusion on patients with underlying malignancy. Transfusion may also suppress the host response to infection. The cellular mechanisms of transfusion-associated immunosuppression may involve macrophage prostaglandin E2 (PGE2) in modulating the host response to cancer and infection. We previously observed that the transfusion of blood increased PGE2 production by unstimulated macrophages. To investigate this PGE2 associated immunosuppression, we studied the effect of transfusion of rats using a physiological stimulus of macrophage PGE2 production, bacterial endotoxin. In the same macrophages, we analysed intracellular oxidative activity. Both allogeneic and syngeneic blood transfusion were associated with increased PGE2 release by macrophages. This stimulation of PGE2 increased with duration of storage of blood. A similar effect of serum indicated that a humoral factor was involved. Endotoxin (50 ng/ml-500 micrograms/ml) stimulated PGE2 production in all transfused subjects. The lowest endotoxin concentration gave proportionately the greatest stimulation. Oxidative activity was down-regulated in macrophages of transfused rats, supporting an immunosuppressive role of PGE2 within the macrophage. An effect of surgery on the oxidative response was also detected.

The influence of dietary essential fatty acids on uterine C20 and C22 fatty acid composition

The effect of dietary fatty acids on uterine fatty acid composition was studied in rats fed control diet or semi-synthetic diet supplemented with 1.5 microliter/g/day evening primrose oil (EPO) or fish oil (FO). Diet-related changes in uterine lipid were detected within 21 days. Changes of 2- to 20-fold were detected in the uterine n-6 and n-3 essential fatty acids (EFA) and in certain saturated and monounsaturated fatty acids. The FO diet was associated with higher uterine C20 and C22 n-3, and the EPO diet, with higher uterine n-6 fatty acid. High uterine C18:2 n-6 was detected in neutral lipid (NL) of rats fed high concentrations of this fatty acid, but there was little evidence of selective incorporation or retention of C18:2 n-6 by uterine NL. The incorporation of EFA into uterine phospholipids (PL) was greater than NL EFA incorporation, and uterine PL n-3/n-6 ratios showed greater diet dependence. Tissue/diet fatty acid ratios in NL and PL also indicated preferential incorporation/synthesis of C16:1 n-9, and C16:0, and there was greater incorporation of C12:0 and C14:0 into uteri of rats fed EPO and FO. Replacement of 50-60% of arachidonate with n-3 EFA in uterine PL may inhibit n-6 EFA metabolism necessary for uterine function at parturition.

Developmental changes in the fatty acids of rat uterus and the influence of dietary essential fatty acids

The effect of age on uterine fatty acid composition was studied in rats fed diets of differing fatty acid composition. Uteri of newly weaned 23-day rats had a higher fatty acid content and a higher proportion of short-chain (less than or equal to C18) fatty acids. Higher incorporation of C less than or equal to 18 fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats compared with adult 240-day rats was detected. Uterine NL incorporated predominantly C less than or equal to 18 fatty acids which may be an important metabolic energy store in developing uterine tissue. Incorporation of C less than or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In contrast, there was selective retention of arachidonic acid (AA) and docosahexanoic acid (DHA) throughout uterine development. An effect of dietary EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked retention of uterine AA when dietary supplies of n-6 EFA were low, but the total AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the three diet groups, and a constant content of AA, EPA and DHA was maintained throughout uterine development, regardless of diet. The degree of n-3 substitution achieved in this study inhibited uterine release of PG and parturition in adult rats.