Relationship of blood transfusion, post-operative infections and immunoreactivity in patients undergoing surgery for gastrointestinal cancer.

BACKGROUND AND OBJECTIVE: The immunosuppression induced by perioperative blood transfusion (BT) and its effect on the incidence of post-surgical infectious complications remains controversial. In this study, the relationship between BT and postoperative infections was investigated in 136 gastrointestinal cancer patients submitted to curative surgery. METHODS: Clinical and laboratory variables, data on postoperative infections, infection risk factors and types of transfusion were analyzed. Immune function was evaluated in 76 patients and compared before and after surgery. RESULTS: The overall postoperative infection rate was 28% for the transfused and 4.6% for the untransfused patients. The univariate analysis of investigated variables indicated that BT, progressive cancer stage, duration of surgery, drains, all had significant association with infection. The multiple logistic regression analysis confirmed BT (p = 0.0028) and advanced cancer stage (p < 0.001) as significant risk factors for the postoperative infections. The results of immunological tests showed no significant differences between transfused and untransfused patient groups, after surgery. Comparing pre- and postoperative data from individual patients, an impairment of natural killer (NK) activity was observed in all patients regardless of their transfusional status; the synthesis of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was also decreased respectively in the untransfused and in the transfused patients. INTERPRETATION AND CONCLUSIONS: These results indicate that other factors, beside BT, can induce immunosuppressive effects in these patients and thus increase their susceptibility to postoperative infections.

Immunoresponsiveness of cancer patients: effect of blood transfusion and immune reactivity of tumor infiltrating lymphocytes.

The immunoreactivity of cancer patients submitted to surgery and perioperatively transfused was investigated. Peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL) were tested for the natural killer (NK) cytotoxic activity, for the in vitro synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). The serum levels and the production of PGE2 by PBMC were significantly higher in patients than in controls, whereas no significant differences in the tested immunological variables emerged between the two groups of subjects. Instead, TIL produced significant larger amounts of spontaneous PGE2 (p < 0.001) and significant lower amounts of IFN-gamma (p < 0.001) and TNF-alpha (p < 0.001) than autologous PBMC, suggesting an involvement of PGE2 in the impairment of the host immunoreactivity at the tumor site. To evaluate the immunomodulating effect of blood transfusion, the patients were reexamined 8 to 20 days after surgery. No differences were found in the NK cytotoxic activity, lymphokine synthesis, serum levels, and production of PGE2 between transfused and untransfused patients. These results do not support the hypothesis that blood transfusions negatively affect the immune response of neoplastic patients.

Effects of blood transfusion on the immune responsiveness and survival of cancer patients: a prospective study.

To evaluate whether blood transfusion exerts an adverse influence on cancer evolution, a prospective clinical and immunologic investigation was carried out on 58 surgical patients with gastric or colorectal adenocarcinoma. None had had previous transfusion; 35 received perioperative transfusion. Among preoperative variables, only red cell count and hemoglobin concentration were significantly reduced in the patients transfused at operation. Other clinical characteristics and immunologic functions (except interferon-gamma release) did not differ significantly from those of untransfused patients. The survival rate of transfused patients, although shorter, was not significantly different from that of untransfused patients. Immunologic tests done after surgery on 30 patients (17 transfused and 13 untransfused) did not show significant differences in the two groups. Significant increases in interleukin-2-stimulated production and immunoglobulin M synthesis were observed in transfused patients after surgery. Patients transfused perioperatively with more than 3 units of blood had some evidence of decreased immune function, but differences were not significant. While shorter survival and some immunologic changes may correlate with the number of transfusions, more patients must be studied to determine whether this relationship will be confirmed.

Investigation on the humoral immune response in patients with gastro-intestinal cancer.

The humoral immune reactivity was studied in patients affected by gastro-intestinal cancer. The number of peripheral B lymphocytes, the concentration of serum immunoglobulins (Ig) and of C3 complement factor and the frequency of circulating immuno complexes (CIC) did not significantly differ between patients and age-matched controls, while the C4 factor level was significantly increased. The frequency of serum monoclonal components (M-components) was higher in the patients than in the elderly subjects. Moreover the results concerning the "in vitro" functional response of patient B lymphocytes showed a significant decrease of the proliferative responses to Staphylococcus Aureus Cowan I (SAC) and a significant increase of the IgG and IgM synthesis by peripheral blood mononuclear cells (PBMC) in unstimulated and pokeweed mitogen (PWM) stimulated cultures. The meaning of these results, taken together with those reported by others, is discussed.

Functional analysis of lymphocytes from two patients affected by common variable immunodeficiency (CVI).

Two patients affected by severe hypogammaglobulinemia classified as CVI were studied. Both patients showed an increase in peripheral T cells and a normal or elevated number of surface immunoglobulin-bearing cells (sIg+); the T cell subsets showed a decrease of CD4 and an increment of CD8 cells with an inversion of the CD4/CD8 ratio. Patient peripheral blood mononuclear cells (PBMC) did not proliferate after Staphylococcus aureus Cowan I (SAC) activation. Moreover, patient PBMC were not able to differentiate into plaque - forming cells (PFC) either spontaneously or after pokeweed mitogen (PWM) stimulation. The immunoglobulin synthesis from patient PBMC stimulated in vitro by PWM was very little as compared to controls. When isolated patient B cells were cultured in the presence of exogenous B cell growth factor (BCGF) and BCGF plus anti-mu and anti-delta antibodies, no proliferation was observed. Taken together the results concerning B cell function of our CVI patients indicate the presence of an intrinsic defect of B cells. These cells are normal in number, but they are not able to leave the resting state, enter the activation state, proliferate and differentiate into Ig secreting cells. Moreover the alteration of the T cell subset proportions seems to suggest an impaired cooperation between B and T cells.

Effects of the allogeneic stimulation on B cell function in thalassaemic polytransfused patients.

The immunological abnormalities of polytransfused patients affected by beta-thalassaemia major have been investigated in relation to B cell function. The spontaneous in vitro production of Ig by patient peripheral mononuclear cells was not modified, while the pokeweed mitogen induced IgM synthesis was significantly reduced. However, by comparing the splenectomized and non-splenectomized patients, this alteration proved to be present only in the splenectomized group. The proliferation of patient peripheral B cells in vitro stimulated with B cell growth factor alone was not significantly enhanced in respect to the controls. These results indicate that in vivo activation state of patient B cells is not different from that of the controls. The stimulation of peripheral B cell with anti-mu or anti-alpha antibodies and anti-mu and anti-alpha antibodies plus B cells growth factor induced a significant increase in proliferative responses of B cells from the splenectomized patients. Taken together, these findings suggest that circulating B cells of thalassaemic polytransfused patients are not hyperactivated. The splenectomy can account for the immunological changes observed in our thalassaemic sample as compared to control group.

Immunoenzymatic determination of immunoglobulins secreted by human peripheral blood lymphocytes in pokeweed mitogen and lipo-polysaccharide stimulated cultures.

Immunoglobulins (Ig) production by peripheral blood mononuclear cells (PBMC) from 27 healthy subjects at the 6th and 12th day of in vitro stimulation by pokeweed mitogen (PWM) or bacterial lipo-polysaccharide (LPS) was investigated. Total IgG, IgA, IgM in the culture supernatants were measured by an enzyme linked immunosorbent assay (ELISA). The average values of Ig production (in ng per ml of culture supernatants) under PWM and LPS stimulation after 12 days of culture are respectively: 3397 and 2557 for IgG, 512 and 374 for IgA, 3172 and 1439 for IgM. The use of PWM and LPS mitogens for stimulating Ig secreting cells may provide insights into the nature of the interacting cells on immune responses and into the pathogenesis of different diseases.

Immune profile alterations in thalassaemic patients.

Aspects of the humoral and cellular immune response have been studied in polytransfused patients with beta-thalassaemia major. Serum immunoglobulins (G, A, M) levels were significantly higher than in controls; reduced C4 serum level and high incidence of circulating immune complexes and anti-nuclear autoantibodies were found in the majority of patients. Marked increases were also observed in absolute and relative numbers of lymphocytes and their subpopulations. Such results suggested that the allogenic stimulation, by frequent transfusion, is the mainly responsible of the immunological alterations observed in these patients.

[Detection of circulating immune complexes with the polyethylene glycol precipitation test: advantages and limitations of the method]. / Ricerca degli immunocomplessi circolanti mediante il test di precipitazione con glicole polietilenico (PEG): vantaggi e limiti del metodo.

The precipitation test with 3.5% PEG has been used to reveal the presence of circulating immuno complexes (IC) in a sample of 130 blood donors. The asymmetry in the O.D. distribution has been corrected by the square root transformation. The positivity threshold has been fixed at the superior extreme of the 95% fiducial interval relative to the transformed data of the control sample, namely at 0.125 O.D.280nm. The correlation between O.D. values obtained with PEG-test and serum concentration of IgG, IgA, IgM, C3 has been studied in 50 of 130 blood donors, 53 patients with gastro-intestinal neoplasm, 73 patients with different forms of the rheumatic disease and 17 patients with cryoglobulinaemia. No significant correlation has been found in normal subjects. Instead, a positive correlation could be demonstrated between O.D. values and IgG concentration both in neoplastic, rheumatic and cryoglobulinemic patients, between O.D. values and IgM concentration in rheumatic patients only; a negative correlation has been found in rheumatic patients with regard to C4. The analytical results are, finally, discusses in relation to the reliability of the method as routine test for the detection of circulating IC.

IgG, IgA and IgM concentration in human sera from different age groups: statistical evaluation.

A statistical analysis is presented of the results obtained from the measure of the serum concentration of IgG, A, M in 773 blood donors. In each of the two groups identified by sex, four subgroups were established according to age in ten years intervals from 20 to 59. On the basis of the results of the analysis, different fiducial intervals of normal values (calculated as mean +/- 2 X standard deviation) have been proposed. 1) A unique interval for IgG: 87-234 U.I. 2) Two intervals for IgA: 54-236 U.I. for subjects under 40 years and 64-270 U.I. for subjects over 40 years. 3) Four intervals for IgM: one for males under 40 years: 65-364 U.I., one for males over 40 years: 57-314 U.I., one for females under 50 years: 47-363 U.I., and one for females over 50 years: 53-434 U.I.