USE OF PREDEPOSIT AUTOLOGOUS BLOOD AND INTRAOPERATIVE AUTOTRANSFUSION IN UROLOGIC CANCER SURGERY LOUIS L. PISTERS, M.D. ZEV WAJSMAN, M.D. From the Department of Surgery, Division of Urology, University of Florida, Gainesville, Florida ABSTRACT-A total of 20 patients underwent major urologic cancer surgery with the combined use of predeposit autologous blood and intraoperative autotransfusion with the Haemonetics Cell Saver. The estimated blood loss ranged from 400 to 2,000 mL (mean 1,208 mL). Total transfusion requirements for the 20 patients were 85.5 units of which 82.5 (96 %) were autologous. Predeposit autologous blood accounted for 53 percent, intraoperative autotransfusion blood 43 percent, and homologous blood 4 percent of the total transfusion requirements. Of the 20 patients in the study, only 1 received homologous blood. There were no complications related to either modality of autotransfusion. Our data suggest that using the combined modalities of predeposit autologous blood donation and intraoperative autotransfusion, major urologic cancer surgery can be performed without homologous blood in most cases. Autotransfusion may be defined as the reinfusion of the patient’s own blood. The three main sources of blood for autotransfusion include preoperative autologous blood donation, intraoperative recovery of blood from the surgical field, and hemodilution. The principal benefit of autologous blood is the reduction or avoidance of complications associated with homologous blood products. These complications include hemolytic, febrile, and allergic reactions, bacterial contamination, alloimmunization, hepatitis, acquired immunodeficiency syndrome (AIDS), and death. lz2It has been appreciated recently that homologous blood transfusion adversely affects multiple components of the immune system. 3-6 Alteration in immune system function is one hypothesis used to explain the increased frequency of postoperative infections seen in patients receiving homologous blood.’ Recent evidence also suggests that homologous blood is associated with decreased disease-free and overall survival in multiple human malignancies. 8 When the guidelines of the American Association of Blood Banks (AABB)g are followed,

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predeposit autologous blood donation is a safe, effective, proved modality of autotransfusion. The use of predeposit autologous blood donation in elective surgical procedures including urologic oncologic surgery has been previously described.‘O Intraoperative autotransfusion, however, is generally thought to be contraindicated in the presence of malignancy.’ To our knowledge, the concept that intraoperative autotransfusion in the presence of malignancy leads to widespread metastasis is unsubstantiated in the literature and, as such, remains a theoretical concern only. The results of anecdotal reports, in fact, support the contention that intraoperative autotransfusion can be used safely in patients with malignant disease.llJ2 Our previous experience with more than 100 patients suggests that intraoperative autotransfusion may be employed safely in urologic cancer surgery. 13-15 There are no previous studies of the combined use of predeposit autologous blood donation and intraoperative autotransfusion in urologic cancer surgery. Herein, we report our experience with 20 patients who underwent

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major urologic cancer surgery using these combined modalities of autologous blood transfusion. Material and Methods From August 1987 to August 1989, 20 patients underwent major urologic cancer surgery at the University of Florida with the combined use of predeposit autologous blood and intraoperative autotransfusion. All patients were male and ranged in age from fifty-four to seventy-six years (mean age of 67). Sixteen patients had adenocarcinoma of the prostate, 14 of whom underwent radical prostatectomy with bilateral pelvic lymph node dissection. Pathologic staging of these 14 patients included 6 Stage B2 patients, 5 Stage Cl, and 3 Stage Dl. ‘lbo of the 16 patients had locally recurrent prostate cancer after iodine-125 seed implantation therapy and required salvage surgery. One of these patients required cystoprostatectomy with resection of the anterior rectal wall, ileal conduit with endorectal pull through for a pathologic Stage C2 adenocarcinoma of the prostate. The second patient was treated with salvage prostatectomy alone for pathologic Stage Cl disease. Four patients had a histologic diagnosis of transitional cell cancer: 3 of the urinary bladder and 1 of the renal pelvis. The 3 patients with bladder cancer were treated with radical cystectomy with urinary diversion for clinical Stage TlNOMO, T3ANOM0, and T3BNOMO disease. The latter two of these three radical cystectomies were performed after systemic chemotherapy and 6,000 cGy of external beam radiation therapy, Pathologic stage in these 3 cases was TONOMO in the first 2 cases and T3BNOMO in the third case. One patient underwent partial nephrectomy for a pathologic Stage TlNOMO tumor of the upper renal pelvis in a kidney with complete ureteral duplication. All patients underwent an extensive history and physical examination with baseline laboratory tests including a complete blood count prior to the initial blood donation. Patients were required to have baseline hematocrit within normal limits (41-53) prior to preoperative donation, adequate peripheral venous access for venipuncture and no evidence of bacterial or viral infection at the time of donation as demonstrated by an oral temperature less than 99.5”F and a normal white blood cell count (4.5-11.0). Those patients who had received myelosuppressive chemotherapy were not al-

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lowed to donate until after their bone marrow had recovered. The frequency of blood donation was usually once weekly and not more than every three days. Donation in the three days preceding surgery was not permitted. On the day of the first donation, every patient was prescribed ferrous sulfate, 325 mg three times a day. Guidelines established by the AABB were followed.e Two patients had stable coronary artery disease with a previous history of myocardial infarction, and 1 patient had clinically significant chronic obstructive pulmonary disease requiring theophylline and bronchodilator medications. The autotransfusion machine (Haemonetics Cell Saver, Haemonetics Corporation, Braintree, MA) was used in all operative cases. This particular autotransfusion machine is currently in widespread use and its mode of operation has been previously described.13 The autotransfusion suction was used meticulously throughout the majority of the operation to recover as much blood as possible. The cell saver blood was reinfused toward the end of the operative procedure after major blood loss was over. Use of sponges was minimized, and any sponges used were squeezed to express blood for autotransfusion. Postoperative evaluation of all patients included a minimum of a physical examination, regular complete blood counts, electrolytes, blood urea nitrogen, creatinines, and other laboratory tests including liver function tests as clinically indicated. Results The amount of preoperative autologous blood donated varied significantly depending on the available time for donation prior to surgery. Data on intraoperative blood loss and replacement of blood were available in all 20 patients. The intraoperative blood loss ranged from 400 mL to 2,200 mL (mean blood loss of 1,208 mL [4.8 U]). Total perioperative autologous predeposit and cell saver blood transfused ranged from 500 mL to 2,000 mL (mean of 1,029 mL [4.1 U]). Intraoperative use of autologous predeposit blood varied from 250 mL to ,Postopera1,000 mL (mean of 325 mL [ 1.3 U]) tive transfusion with autologous predeposit blood ranged from 0 mL to 500 mL (mean of 250 mL [l.O U]). Fifty-six percent of all autologous predeposit blood transfused was given intraoperatively. Intraoperative transfusion with cell saver blood ranged from 150 mL to 1,000

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mL (mean of 454 mL [ 1.8 U]) .The hematocrit level at the time of discharge home from the hospital ranged from 25 to 40 (mean of 32%). The total transfusion requirements for the 20 patients were 85.5 U of which 82.5 U (96%) were autologous blood. Predeposit autologous blood accounted for 53 percent of the total transfusion requirements, intraoperative cell saver blood accounted for 43 percent, and exogenous blood accounted for the remaining 4 percent. Of the 20 patients in the study, only 1 patient received homologous blood. This patient was able to donate only 1 U of predeposit blood due to time constraints and he required 3 U of homologous blood. This patient underwent partial nephrectomy for a pathologic Stage TlNOMO transitional cell cancer of the upper pole renal pelvis in a kidney with complete ureteral duplication. The estimated blood loss for the procedure was 1,400 mL and the patient received 250 mL of cell saver blood. Use of the autotransfusion machine resulted in the recovery and autologous transfusion of 500 mL or more of blood in 10 of the 12 patients in whom intraoperative blood loss exceeded 1,000 mL. In contrast, none of the 8 patients with an intraoperative loss of blood less than 1,000 mL received 500 mL or more of cell saver blood. Overall 9,080 mL of cell saver blood was reinfused from a total of 24,150 mL of blood lost intraoperatively giving a recovery efficiency of 38 percent. There were no complications directly related to either modality of autologous transfusion. In particular, patients with stable coronary artery disease and those who had received myelosuppressive chemotherapy had no complications related to predeposit autologous blood donation, although these patients were few in number. Comment The safest blood a patient can receive is his own. Patient concern about prospective blood transfusion has never been higher and has resulted in increased patient demand for autologous transfusion. Patients may benefit psychologically through predeposit autologous blood donation by being more involved in their own care. Use of autologous blood has been endorsed by many medical organizations including the American Medical Association. l The immunosuppressive effects of homologous blood are well known and clinically useful in organ transplantation, where homologous

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blood is used to increase renal allograft survival. Homologous blood transfusion has been shown to adversely affect multiple components of the immune system including an impairment in macrophage function3 a reduction in the proliferative response of leukocytes in lymph nodes,4 diminished helper to suppressor lymphocyte ratios and natural killer cell activity,5 and an increase in the synthesis of the immunosuppressive metabolite, prostaglandin E. Rarely, graft versus host disease has been reported in cancer patients receiving homologous blood products who were treated with systemic chemotherapy and not bone marrow transplantation.le The clearest benefit of autologous blood is the avoidance of the infectious complications of homologous blood. Recently, a screening test for hepatitis C has become available, and as this test is widely implemented, the incidence of transfusion-related hepatitis should decrease.17 In addition, 2 percent of the documented instances of AIDS are directly related to the receipt of homologous blood products.ls Even with current screening of blood donations for antibody to human immunodeficiency virus (HIV), there remains a small but identifiable risk of HIV infection for recipients of screened blood.le This risk is hard to quantify but has been estimated at between 1:40,000 and 1:250,000 transfusions.2 In addition, homologous blood appears to be an independent risk factor for postoperative infectious complications7 This effect may be mediated through immune mechanisms and has been supported by multiple animal studies.20 A number of retrospective studies have suggested early tumor recurrence with decreased disease-free and overall survival in cancer patients receiving homologous blood products.8.21.22 Most of these retrospective studies have used multivariate analysis to exclude the independent effect of multiple variables (such as age, stage of disease, duration of surgery, etc.) on the disease-free and overall survival of cancer patients. At least two studies demonstrate an apparent dose-response relationship, with patients receiving larger numbers of transfusions having poorer outcomes.21J2 The combined data, particularly those from the studies using multivariate analysis of multiple risk factors, suggest very strongly that homologous perioperative blood transfusion itself is an independent variable related to decreased survival in multiple tumor systems including cancer of

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the colon, rectum, lung, and soft tissue sarcomas.8,21*22 In a rat sarcoma model, allogenic blood transfusions increase the rate of tumor growth and decrease mean survival times.23 This decreased survival seen in patients receiving homologous blood may also be mediated through immunologic mechanisms.*,22,23 Intraoperative autotransfusion has been used extensively for more than a decade in a variety of surgical settings including cardiac, vascular, orthopedic, gynecologic procedures, and treatment of traumatic injuries. It has been clearly shown to be safe, cost-effective and in some instances, life-saving. Despite these widespread applications, the presence of a malignant tumor is still generally regarded as a contraindication to the use of intraoperative autotransfusion.’ Although it appears likely that intraoperative autotransfusion may lead to the systemic infusion of cancer cells,24,25 the concept that intraoperative autologous transfusion of cancer cells leads to widespread metastases is unsubstantiated in the literature. The biologic significance of circulating tumor cells found at the time of surgery is unclear at the present time. In early studies of circulating cancer cells, many normal cellular elements of blood such as megakaryocytes and granulocytes were mistaken for cancer cells.2e In a more recent study of 100 patients in which tumor cells were carefully identified at the time of surgery, Griffiths et al. 27 found circulating cancer cells present in 57 percent of patients undergoing surgery for carcinoma of the colon. Fifty-six percent of patients in whom circulating tumor cells were found at the time of surgery were alive at five-year follow-up.27 This finding has been corroborated by other investigators who have concluded that the presence or absence of tumor cells in the circulation is of little or no prognostic significance.2* Intraoperative autotransfusion has been widely used in major urologic cancer surgery at the University of Florida since July 1984, with no evidence thus far for dissemination of tumor or decreased survival in patients receiving intraoperative autotransfusion. At the time of publication of our experience with intraoperative autotransfusion in radical cystectomy for bladder cancer, mean follow-up was twentyfour months.13 In longer follow-up of these bladder cancer patients (mean follow-up 44 months), survival rates remain in keeping with the reported survival rates for patients undergoing radical cystectomy for bladder cancer. l5 All

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cancer patients are fundamentally at risk for development of metastasis. The focus of the controversy surrounding the use of intraoperative autotransfusion in cancer surgery centers on the increment in risk for metastasis imposed by using intraoperative autotransfusion. The increment in risk for metastasis imposed by intraoperative autotransfusion must be very low in bladder cancer, as there was no survival difference demonstrated in these studies13,15 compared with historical controls. We recognize that further studies including prospective randomized studies of intraoperative autotransfusion in cancer patients need to be performed before one can safely conclude that the risk of metastasis from intraoperative autotransfusion is negligible. The current study as well as our previous published experience with the use of intraoperative autotransfusion in urologic cancer surgery provide firm evidence to justify the performance of such randomized controlled studies. By combining predeposit autologous blood donation and intraoperative autotransfusion, a significant volume of autologous blood can be delivered. Two patients with estimated blood losses of 2,200 and 2,000 mL received a total of 1,800 mL (7 U) and 2,000 mL (8 U) of autologous blood, respectively. The possibility of performing an operation without homologous blood using these two combined modalities will depend on multiple factors including the estimated blood loss of the procedure, the amount of predeposit autologous blood donated, the efficiency of blood recovery intraoperatively, the status of the patient’s bone marrow (rate of erythropoiesis), and the patient’s overall medical condition and ability to tolerate a low postoperative hematocrit. The single patient in this study who received homologous blood donated only 1 U of predeposit autologous blood. If one arbitrarily assumes that a hematocrit of 25 percent at the time of discharge home is acceptable and that each unit of cell saver blood raises the hematocrit by 3 percent, then we estimate that 7 of the 19 patients in this study who avoided homologous blood required intraoperative autotransfusion to do so. Many predeposit autologous blood programs require that a hematocrit around 34 percent be maintained during donation. Within this hematocrit range, the degree of anemia experienced is insufficient to initiate an adequate increase in erythropoietin production.2e However, recombinant human erythropoietin has been shown

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recently to increase predeposit autologous blood yield by a significant degree (41% increase in mean red-cell volume) .30 Since major urologic surgery is associated with significant blood loss, the use of recombinant human erythropoietin may play a significant role in the preparation of these patients for surgery. Our data suggest that the combined modalities of predeposit autologous blood donation and intraoperative autotransfusion deliver sufficient volumes of autologous blood to allow most urologic surgical procedures to be performed without homologous blood.

11. Clover JL, and Broadie TA: Intraoperative autotransfusion, Surg Annu 16: 39 (1984). 12. Montie JE, et al: Resection of large inferior vena caval thrombi from renal cell carcinoma with the use of circulatory arrest, J Urol 139: 25 (1988). 13. Hart OJ, Klimberg I, and Wajsman Z: Intraoperative autotransfusion in radical cystectomy for carcinoma of the bladder, Surg Gynecol Obstet 168: 302 (1989). 14. Klimberg I, Sirois R, Wajsman Z, and Baker J: Intraoperative autotransfusion in urologic oncology, Arch Surg 121: 1326 (1986). 15. Hart OJ, Klimberg I, and Wajsman Z: Intraoperative autotransfusion in patients with invasive bladder cancer: long term followup (abstr 1252), J Urol 141: 478A (1989). 16. Kessinger A, et al: Graft versus host disease following transfusion of normal blood products to patients with malignancies, J Surg Oncol36: 206 (1987). 17. Kuo G, et al: An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis, Science 244: 362 (1989). 18. Centers for Disease Control: AIDS-Recommendations and guidelines, November 1982-December 1987, Atlanta, GA: Public Health Service, Department of Health and Human Services, April, 1988. 19. Ward JW, et al: Transmission of human immunodeficiency virus (HIV) by blood transfusion screened as negative for HIV antibodv. N Enel I Med 318: 473 (1988). 20. cayma& JP, et al: Effect of varying number and volume of transfusions on mortality rate following septic challenge in an animal model, World J Surg 11: 387 (1987). a cause 21. Blumberg N, et al: Further evidence supporting and effect relationship between blood transfusion and earlier cancer recurrence, Ann Surg 207: 410 (1988). 22. Rosenberg SA, Seipp CA, White DE, and Wesley R: Perioperative blood transfusions are associated with increased rates of recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities, J Clin Oncol3: 698 (1985). 23. Waymack JP, and Chance WT: Effect of blood transfusions on immune function: IV effect on tumor growth, J Surg Oncol39: 159 (1988). 24. Yaw PB, et al: Tumor cells carried through autotransfusion, JAMA 231: 490 (1975). 25. Dale RF, et al: Separation of malignant cells during autotransfusion, Br J Surg 75: 581 (1988). 26. Cole WH: The mechanisms of spread of cancer, Surg Gynecol Obstet 137: 853 (1973). 27. Griffiths TD. et al: Carcinoma of the colon and rectum: circulating malignant cells and five-year survival, Cancer 31: 226 (1973). 28. Engell HC: Cancer cells in the blood: a five to nine year follow up study, Ann Surg 149: 457 (1959). 29. Kickler TS, and Spivak JL: Effect of repeated whole blood donations on serum immunoreactive erythropoietin levels in autologous donors, JAMA 260: 65 (1988). collection of 30. Goodnough L, et al: Increased preoperative autologous blood with recombinant human erythropoietin therapy, N Engl J Med 321: 1163 (1989).

University of Florida Department of Surgery Division of Urology J.H.M.H.C., Box J-247 Gainesville, Florida 32610-0247 (DR. WAJSMAN) ACKNOWLEDGMENT. To P W. T. Pisters and A. Smith for assistance in the preparation of this article. References 1. Council on Scientific Affairs: Autologous blood transfusions, JAMA 256: 2378 (1986). 2. FDA Drug Bulletin: Use of Blood Components, Rockville, MD: Dept. of Health, Education and Welfare, Public Health Service, Food and Drug Administration, July 19 (2), 1989. 3. Waymack JP, et al: Effect of transfusion on immune function in a traumatized animal model, Arch Surg 121: 50 (1986). 4. Guigley RL, Wood KJ, and Morris PJ: Investigation of the mechanism of active enhancement of renal allograft survival by blood transfusion, Immunology 63: 373 (1988). 5. Kaplan J, Sarnaik S, Citlin J, and Lusher J: Diminished helper/suppre&.or lymphocyte ratios and natural killer activity in recinients of retreated blood transfusions. Blood 64: 308 (1984). 6: Waymack JR et al: Effect of blood transfusions on immune function, Arch Surg 122: 56 (1987). 7. Tartter PI: Blood transfusion and infectious complications following colorectal cancer surgery, Br J Surg 75: 789 (1988). 8. Blumberg N, and Heal JM: Perioperative blood transfusion and solid tumor recurrence-a review, Cancer Invest 5: 615 (1987). 9. American Association of Blood Banks: Standards for blood banks and transfusion services. Arlington, VA: Standards Committee, American Association of Blood Banks, 1989. 10. Swanson DA, Lo RK, and Lichtiger B: Predeposit autologous blood transfusions in patients undergoing irradiation and radical cystectomy, J Urol 130: 892 (1983).

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Use of predeposit autologous blood and intraoperative autotransfusion in urologic cancer surgery.

A total of 20 patients underwent major urologic cancer surgery with the combined use of predeposit autologous blood and intraoperative autotransfusion...
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