Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized 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. Oral prophylaxis with neomycin and erythromycin in colorectal surgery. More proof for efficacy than failure. Prophylactic antibiotics in elective colorectal surgery. A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. Treatment of postoperative ileus after bowel surgery with low-dose intravenous erythromycin. Preoperative epoetin alfa in colorectal surgery: a randomized, controlled study. Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia. Peroperative systemic prophylaxis in colorectal surgery.
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. 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. In an open, prospective, and randomized investigation on the prophylactic efficacy of peroral neomycin sulfate-erythromycin base vs intravenous ceftriaxone-metronidazole preparation in colorectal surgery, no significantly diverging results between regimens were recorded (1/27 [3.7%] and 2/27 [7.4%] wound infections, respectively). Commentary is made about the diverging results from earlier studies on antimicrobial prophylaxis and on the multifactorial causality of surgical infection. We believe that variables such as physical condition of the patients, virulence and local resistance patterns of bacteria, and technical skill of the surgeons are far more important in regard to the postoperative outcome concerning septic complications than is the choice of proper antibiotics. Thus, to determine the efficacy of antimicrobial prophylaxis, we call for larger investigations in the future, preferably double-blind, where it is possible to better control and diminish the influence of determinants other than the antibiotics being compared. A randomized prospective study was conducted on 194 patients who underwent elective colorectal surgery for carcinoma. All patients received the same mechanical bowel preparation. In addition, patients in group A received oral neomycin and erythromycin base; patients in group B received systemic metronidazole and gentamicin, while patients in group C received both oral and systemic antibiotics. Postoperative septic complications related to colorectal surgery occurred in 27.4 per cent, 11.9 per cent and 12.3 per cent respectively in groups A, B and C (chi 2 = 7; P less than 0.05). The incidence of sepsis in groups B and C was almost identical. Patients who received oral antibiotics alone (group A) had significantly higher risks of postoperative sepsis when compared with patients in either group B or group C (P less than 0.05). As there is no additional advantage of combining oral and systemic antibiotics, we recommend systemic metronidazole and gentamicin to be used with mechanical bowel preparation in elective colorectal surgery. A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.
                This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.
                Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.
                Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.
                This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased. Treatment of postoperative ileus remains unsatisfactory. Erythromycin (EM), a macrolide antibiotic, has prokinetic effects on the gut. We investigated whether intravenous erythromycin decreases the time to the return of normal bowel function after bowel surgery in patients with bladder cancer and interstitial cystitis who have undergone cystectomy and urinary diversion.
                We conducted a double-blind, randomized, placebo-controlled study of 22 volunteers. On the first postoperative day, patients began receiving intravenous erythromycin (125 mg) or placebo every 8 hours (maximum of 21 doses). The patients' ability to tolerate a general diet and return of bowel function was monitored.
                A general diet was tolerated at a median of 9 days postoperatively for the EM arm and 8 for the placebo arm (P = 0.60). The first bowel sounds were detected at an average of 2 postoperative days for the EM arm and 3 for the placebo arm (P = 0.88). First flatus was present an average of 5 days postoperatively for both study arms (P = 0.35). The first bowel movement was present an average of 6 days postoperatively for the EM arm and 5 for the placebo arm (P = 0.98).
                No significant difference was found between EM and placebo with regard to the onset of bowel sounds, passage of flatus, passage of the first bowel movement, and the time to tolerate a general diet. These data indicate that erythromycin is not useful in improving postoperative bowel function. 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. Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC).
                A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks.
                Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment.
                An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely. In an effort to reduce infection rates in elective colorectal surgery to acceptable levels without oral non-absorbable antimicrobials, using only a short course of systemic antimicrobials, 50 patients were studied in a multicentre trial. Each patient received metronidazole for anti-anaerobic coverage. The anti-aerobic coverage consisted of netilmicin, cefuroxime or placebo, administered in a double-blind manner. Five out of 36 evaluable patients had an infection at the operation site. Two patients had peritonitis (one metronidazole-netilmicin and one metronidazole-placebo) and three had a wound abscess in the abdominal wall (all metronidazole-placebo). It is concluded that a short course of peroperative systemic prophylaxis with metronidazole and netilmicin or cefuroxime--without the use of oral non-absorbable antimicrobials--gave acceptable results in the centres studied.
There is no sufficient evidence to date to recommend pre and peri-operative erythropoietin use in colorectal cancer surgery.