Preoperative epoetin alfa in colorectal surgery: a randomized, controlled study. Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study. Recombinant human erythropoietin and hemoglobin concentration at operation and during the postoperative period: reduced need for blood transfusions in patients undergoing colorectal surgery--prospective double-blind placebo-controlled study. Randomized multicentre trial of the influence of recombinant human erythropoietin on intraoperative and postoperative transfusion need in anaemic patients undergoing right hemicolectomy for carcinoma.
Colorectal cancer patients are often anemic before surgery, and this leads to an increased requirement for allogeneic blood transfusion. This may result in transfusion-induced immunosuppression, which in turn leads to increased morbidity and possibly an increased rate of tumor relapse. We investigated the possible benefits of perioperative epoetin alfa administration in anemic patients to correct hemoglobin levels and reduce transfusion needs.
                A total of 223 colorectal cancer patients with anemia scheduled for surgery were randomized to a group that received epoetin alfa 150 or 300 IU/kg/day subcutaneously for 12 days (day -10 to +1) or to a control group. All received iron (200 mg/day by mouth) for 10 days before surgery. Hemoglobin levels, hematocrit, and the number of blood units transfused were recorded.
                A total of 204 patients were eligible for analysis. Mean hemoglobin levels and hematocrit were significantly higher in the 300 IU/kg group than in the control group, both 1 day before surgery (hemoglobin, P = .008; hematocrit, P = .0005) and 1 day after surgery (hemoglobin, P = .011; hematocrit, P = .0008). Blood loss during and after surgery was similar in all groups. Patients who received epoetin alfa 300 IU/kg required significantly fewer perioperative transfusion units than control patients (.81 vs. 1.32; P = .016) and significantly fewer postoperative units (.87 vs. 1.33; P = .023). There were no significant differences in the number of units in the 150 IU/kg group.
                Preoperative epoetin alfa (300 IU/day) increases hemoglobin levels and hematocrit in colorectal surgery patients. These effects are associated with a reduced need for perioperative and postoperative transfusions. Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery, To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation, it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately.
                In a double-blind randomized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2. Twenty patients were randomized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group.
                In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed. Preoperative hemoglobin response in the erythropoietin group (p = 0.069) was paralleled by a highly significant reticulocyte increase (p = 0.0004). However, frequency of blood transfusion was not different between both study groups (erythropoietin, 1.82 +/- 0.80 units/ patient; placebo, 1.80 +/- 0.97 units/patient). If iron availability was analyzed, a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis (p < 0.001).
                These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin; however, clinical efficacy is to be expected only in selected patients with high iron availability, which calls for further studies combining erythropoietin and parenteral iron application. In a double-blind placebo-controlled study we investigated the effect of recombinant human erythropoietin (r-HuEPO), on the perioperative hemoglobin concentration and the use of blood transfusions in patients undergoing elective colorectal surgery with a preoperative hemoglobin level </=8.5 mmol/L. Altogether 100 were included, and 81 patients could be evaluated. A total of 38 patients received r-HuEPO in a dose of 300 IU/kg body weight on day 4 before surgery and 150 IU/kg daily for the following 7 days; 43 patients received placebo. In addition, all patients received daily doses of 200 mg iron orally for 4 days before surgery. There were no differences between the two groups with regard to sex, height, weight, serum electrolytes, and liver function tests at study entry. The preentry hemoglobin concentration was similar in the two groups, with a median value of 7.9 (range 5.3-8.5) mmol/L in the erythropoietin group and 7.6 (5.1-8.5) mmol/L in the placebo group. On the day of surgery the median hemoglobin concentration was 7.8 (5. 3-9.2) mmol/L in the erythropoietin group and 7.2 (4.6-8.5) mmol/L in the placebo group (p < 0.05). On postoperative days 3 and 7 the values were 7.2 (5.3-8.2) and 7.5 (5.4-9.4) mmol/L, respectively, in the erythropoietin group compared to 6.7 (5.2-7.8) and 6.9 (5.1-8.6) mmol/L in the placebo group (p < 0.01). At discharge the hemoglobin concentration was 7.8 (5.9-8.8) mmol/L in the erythropoietin group and 7.2 (5.4-8.6) mmol/L in the placebo group (p < 0.002). The blood loss during operation was similar in the two groups. In the erythropoietin group the median value was 280 ml (range 25-2000 ml), with the lower and upper quartiles 150 and 500 ml, respectively. In the placebo group the blood loss was median 300 ml (range 50-1800 ml), with the lower and upper quartiles 200 and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0-6) units compared to 1.6 (0-9) units in the control group (p < 0.05). In conclusion, the hemoglobin concentration at the time of surgery and during the week following surgery was significantly higher in the group of patients receiving r-HuEPO perioperatively compared to the placebo group together with a significant lower use of blood transfusions in the r-HuEPO group. However, the clinical implications of these findings has yet to be proven. The possible immunosuppressive effect of blood transfusion and its influence on survival after surgery for cancer makes it worthwhile to seek methods to avoid transfusion wherever possible. Patients with right-sided colonic cancer are frequently anaemic. Such patients were entered into a study that employed erythropoietin to avoid homologous transfusion.
                In a prospectively randomized double-blind placebo-controlled multicentre trial, patients with moderate anaemia (haemoglobin concentration greater than 8.5 g/dl and less than or equal to 13.5 g/dl) presenting with right-sided colonic cancer and scheduled for hemicolectomy were treated with recombinant human erythropoietin (epoetin beta) 20,000 units/day subcutaneously or placebo for at least 10 days over the operative period.
                Perioperative treatment with epoetin beta was well tolerated and there were no significant differences in morbidity and mortality. Following hemicolectomy, median cumulative blood loss in the two groups was similar (epoetin beta 440 ml versus placebo 345 ml). Sixteen (33 per cent) of 48 patients treated with epoetin beta and 15 (28 per cent) of 54 in the placebo group received perioperative blood transfusions (P not significant). The increase in reticulocyte count between baseline and the last preoperative value was more pronounced in the epoetin beta group than in those receiving placebo (P = 0.036).
                Despite the perioperative administration of 20,000 units erythropoietin per day for at least 10 days, it was not possible to reduce the intraoperative and postoperative transfusion need. None the less, a positive change in the haematological variables of treated patients was clearly discernible. The negative result may be due to the short treatment interval and to iron deficiency, which was present in the majority of patients. The general change of attitude towards allogeneic blood transfusion is demonstrated by the overall low frequency of blood transfusion in this study.
There is no sufficient evidence to date to recommend pre and peri-operative erythropoietin use in colorectal cancer surgery.