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Влияние трансфузии донорских и аутоэритроцитов на онкологические результаты хирургического лечения больных раком почки с опухолевым венозным тромбозом
DOI: 10.26442/18151434.2023.1.202103
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
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Volkova MI, Feoktistov PI, Begaliev AK, Shin AR, Matveev VB, Prikhodchenko AO. Effect of transfused donor and autoerythrocytes on the oncological outcomes of surgical treatment in patients with renal cell carcinoma with tumor-related venous thrombosis: observational study. Journal of Modern Oncology. 2023;25(1):133–139.
DOI: 10.26442/18151434.2023.1.202103
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Цель. Изучить частоту нарушений системы гемостаза при использовании интраоперационной АРА, а также влияние АРА и трансфузий ДЭ на специфическую (СВ), безрецидивную (БРВ) и беспрогрессивную (БПВ) выживаемость пациентов с почечно-клеточным раком (ПКР) после НЭТЭ.
Материалы и методы. В обсервационное исследование включены медицинские данные 507 больных ПКР с опухолевым тромбозом НПВ, оперированных в объеме НЭТЭ. Медиана объема кровопотери составила 4000 мл [2000–6500]. В 312 (61,5%) наблюдениях для возмещения кровопотери применили АРА без лейкоцитарного фильтра (медиана объема возвращенных аутоэритроцитов – АЭ – 1140 мл [700; 1900]). Трансфузия ДЭ потребовалась в 387 (76,3%) случаях, медиана количества перелитых доз ДЭ составила 3 [1; 5]. Выписаны из стационара 475 (93,7%) больных. Медиана наблюдения за всеми выжившими пациентами составила 24 (1–189) мес.
Результаты. Показания к кровозамещению (ДЭ и АЭ) прямо взаимосвязаны с категориями pN (r=0,101; p=0,024) и pT (r=0,091; p=0,040) соответственно. Использование АЭ не оказывало значимого влияния на частоту нарушений системы гемостаза и коагулопатических осложнений по сравнению с другими методами замещения кровопотери: 6,8% (21/311) vs 4,7% (9/193); p=0,227; 5,1% (16/311) vs 4,1% (8/193); p=0,394 соответственно. Не выявлено влияния АРА на СВ, БРВ (для радикально оперированных пациентов) и БПВ (для подвергнутых циторедуктивным операциям больных) после НЭТЭ. Отмечено ухудшение СВ пациентов, получавших трансфузии ДЭ, по сравнению с больными, которым переливание ДЭ не производилось (отношение рисков 0,4; 95% доверительный интервал 0,1–0,9; p=0,048). Влияния переливаний ДЭ на БРВ и БПВ не выявлено.
Заключение. Интраоперационная АРА является эффективным и безопасным методом коррекции анемии, не приводящим к повышению риска развития коагулопатических осложнений и снижению показателей выживаемости. Отказ от лейкоцитарного фильтра в процессе заготовки АЭ не влечет за собой ухудшения среднесрочных онкологических результатов хирургического лечения ПКР с опухолевым тромбозом НПВ. Влияние трансфузии ДЭ на выживаемость больных ПКР после НЭТЭ требует дальнейшего изучения.
Ключевые слова: рак почки, нефрэктомия, тромбэктомия, cell-saver, аппаратная реинфузия аутоэритроцитов, донорские эритроциты, выживаемость
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Background. The only effective treatment for renal cell carcinoma with tumor inferior vena cava (IVC) thrombosis is surgery. Nephrectomy with thrombectomy (NETE) is usually associated with clinically significant blood loss. The role of blood-sparing methods using autoerythrocyte reinfusion device (ARD) or replacement of blood loss with donor erythrocytes (DE) on the outcomes of NETE has not been well studied.
Aim. To study the rate of hemostasis disorders with intraoperative ARD use, as well as the effect of ARD and DE transfusions on specific (SS), relapse-free (RFS), and progression-free (PFS) survival of patients with renal cell carcinoma (RCC) after NETE.
Materials and methods. The observational study included medical data of 507 patients with RCC and tumor IVC thrombosis operated after NETE. The median volume of blood loss was 4000 [2000–6500] mL. In 312 (61.5%) patients, ARD without a leukocyte filter was used to compensate for blood loss (median volume of reinfused autoerythrocytes – AE was 1140 [700; 1900] mL). Transfusion of DE was required in 387 (76.3%) cases; the median number of DE transfused doses was 3 [1; 5]; 475 (93.7%) patients were discharged from the hospital. The median follow-up of all surviving patients was 24 (1–189) months.
Results. Indications for blood transfusions (DE and AE) were directly correlated to the pN (r=0.101; p=0.024) and pT (r=0.091; p=0.040) categories, respectively. The use of AE had no significant effect on the rate of hemostasis disorders and coagulopathic complications compared to other methods of blood loss replacement: 6.8% (21/311) vs 4.7% (9/193), p=0.227; 5.1% (16/311) vs 4.1% (8/193), p=0.394, respectively. ARD had no effect on SS, RFS (after radical surgery), and PFS (after cytoreductive surgery) after NETE. There was a reduction of SS in patients who received DE transfusions compared with those who did not (hazard ratio 0.4; 95% confidence interval 0.1–0.9; p=0.048). The effects of DE transfusions on RFS and PFS were not identified.
Conclusion. Intraoperative ARD use is an effective and safe method of correcting anemia, which does not increase the risk of coagulopathic complications or decrease survival rates. The non-use of the leukocyte filter during AE preparation does not worsen the medium-term oncological results of RCC surgical treatment with tumor IVC thrombosis. The effect of DE transfusion on the survival of RCC patients after NETE requires further research.
Keywords: renal cell carcinoma, nephrectomy, thrombectomy, cell-saver, autoerythrocyte reinfusion device, donor erythrocytes, survival
2. Parra J, Drouin SJ, Hupertan V, et al. Oncological outcomes in patients undergoing radical nephrectomy and vena cava thrombectomy for renal cell carcinoma with venous extension: a single-centre experience. Eur J Surg Oncol. 2011;37(5):422-8.
3. Helfand BT, Smith ND, Kozlowski JM, Eskandari MK. Vena cava thrombectomy and primary repair after radical nephrectomy for renal cell carcinoma: Single-center experience. Ann Vasc Surg. 2011;25(1):39-43.
4. Delis S, Dervenis C, Lytras D, et al. Liver transplantation techniques with preservation of the natural venovenous bypass: effect on surgical resection of renal cell carcinoma invading the inferior vena cava. World J Surg. 2004;28(6):614-9.
5. Vamvakas EC. Perioperative blood transfusion and cancer recurrence: meta-analysis for explanation. Transfusion. 1995;35(9):760-8.
6. Amato AC, Pescatori M. Effect of perioperative blood transfusions on recurrence of colorectal cancer: meta-analysis stratified on risk factors. Dis Colon Rectum. 1998;41(5):570-85.
7. Soubra A, Zabell JR, Adejoro O, Konety BR. Effect of perioperative blood transfusion on mortality for major urologic malignancies. Clin Genitourin Cancer. 2015;13(3):e173-81.
8. Linder BJ, Thompson RH, Leibovich BC, et al. The impact of perioperative blood transfusion on survival after nephrectomy for non-metastatic renal cell carcinoma (RCC). BJU Int. 2014;114(3):368-74.
9. Atzil S, Arad M, Glasner A, et al. Blood transfusion promotes cancer progression: a critical role for aged erythrocytes. Anesthesiology. 2008;109(6):989-97.
10. Upile T, Jerjes W, Mahil J, et al. Blood product transfusion and cancer prognosis. Clin Adv Hematol Oncol. 2009;7(10):656-61.
11. Kozek-Langenecker SA, Ahmed AB, Afshari A, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol. 2017;34(6):332-95. DOI:10.1097/EJA.0000000000000630
12. Tran DH, Wong GT, Chee YE, Irwin MG. Effectiveness and safety of erythropoiesis-stimulating agent use in the perioperative period. Expert Opin Biol Ther. 2014;14(1):51-61.
13. Popovsky MA, Devine PA, Taswell HF. Intraoperative autologous transfusion. Mayo Clin Proc. 1985;60(2):125-34.
14. Buth J, Raines JK, Kolodny GM, Darling RC. Effect of intraoperative autotransfusion on red cell mass and red cell survival. Surg Forum. 1975;26:276‑8.
15. Ray JM, Flynn JC, Bierman AH. Erythrocyte survival following intraoperative autotransfusion in spinal surgery: an in vivo comparative study and 5-year update. Spine (Phila Pa 1976). 1986;11(9):879-82.
16. Homann B, Zenner HP, Schauber J, Ackermann R. Tumor cells carried through autotransfusion. Are these cells still malignant? Acta Anaesthesiol Belg. 1984;35(Suppl.):51-9.
17. Miller GV, Ramsden CW, Primrose JN. Autologous transfusion: an alternative to transfusion with banked blood during surgery for cancer. Br J Surg. 1991;78(6):713‑5.
18. Klezl P, Pospisilova E, Kolostova K, et al. Detection of Circulating Tumor Cells in Renal Cell Carcinoma: Disease Stage Correlation and Molecular Characterization. J Clin Med. 2020;9(5):1372.
19. Oefelein MG, Kaul K, Herz B, et al. Molecular detection of prostate epithelial cells from the surgical field and peripheral circulation during radical prostatectomy. J Urol. 1996;155(1):238-42.
20. Weiss L. Metastatic inefficiency: causes and consequences. Cancer Rev. 1986;3:1-24.
21. Frietsch T, Steinbicker AU, Horn A, et al. Safety of Intraoperative Cell Salvage in Cancer Surgery: An Updated Meta-Analysis of the Current Literature. Transfus Med Hemother. 2022;49(3):143-57.
22. Moskowitz DM, Perelman SI, Cousineau KM, et al. Multidisciplinary management of a Jehovah’s Witness patient for the removal of a renal cell carcinoma extending into the right atrium. Can J Anaesth. 2002;49(4):402-8.
23. Casey RG, Raheem OA, Elmusharaf E, et al. Renal cell carcinoma with IVC and atrial thrombus: a single centre’s 10 year surgical experience. Surgeon. 2013;11(6):295-9.
24. Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology. Arch Surg. 1986;121(11):1326-9.
25. Lyon TD, Ferroni MC, Turner RM, et al. Shortterm outcomes of intraoperative cell saver transfusion during open partial nephrectomy. Urology. 2015;86(6):1153-8.
26. Zhang X, Guo X, Zong Y. CTCs detection from intraoperative salvaged blood in RCC–IVC thrombus patients by negative enrichment and iFISH identification: a preliminary study. BMC Urol. 2021;21(1):89.
27. Carless PA, Henry DA, Moxey AJ, et al. Cell salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2010;3:CD001888.
28. Domen RE. Adverse reactions associated with autologous blood transfusion: evaluation and incidence at a large academic hospital. Transfusion. 1998;38(3):296‑300.
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1. Volkova MI, Vashakmadze NL, Klimov AV, et al. Prognosis of patients operated on for renal cell carcinoma and tumor venous thrombosis: experience of the Urology Clinics, N.N. Blokhin National Medical Research Center of Oncology. Cancer Urology. 2021;17(3):19-28 (in Russian).
2. Parra J, Drouin SJ, Hupertan V, et al. Oncological outcomes in patients undergoing radical nephrectomy and vena cava thrombectomy for renal cell carcinoma with venous extension: a single-centre experience. Eur J Surg Oncol. 2011;37(5):422-8.
3. Helfand BT, Smith ND, Kozlowski JM, Eskandari MK. Vena cava thrombectomy and primary repair after radical nephrectomy for renal cell carcinoma: Single-center experience. Ann Vasc Surg. 2011;25(1):39-43.
4. Delis S, Dervenis C, Lytras D, et al. Liver transplantation techniques with preservation of the natural venovenous bypass: effect on surgical resection of renal cell carcinoma invading the inferior vena cava. World J Surg. 2004;28(6):614-9.
5. Vamvakas EC. Perioperative blood transfusion and cancer recurrence: meta-analysis for explanation. Transfusion. 1995;35(9):760-8.
6. Amato AC, Pescatori M. Effect of perioperative blood transfusions on recurrence of colorectal cancer: meta-analysis stratified on risk factors. Dis Colon Rectum. 1998;41(5):570-85.
7. Soubra A, Zabell JR, Adejoro O, Konety BR. Effect of perioperative blood transfusion on mortality for major urologic malignancies. Clin Genitourin Cancer. 2015;13(3):e173-81.
8. Linder BJ, Thompson RH, Leibovich BC, et al. The impact of perioperative blood transfusion on survival after nephrectomy for non-metastatic renal cell carcinoma (RCC). BJU Int. 2014;114(3):368-74.
9. Atzil S, Arad M, Glasner A, et al. Blood transfusion promotes cancer progression: a critical role for aged erythrocytes. Anesthesiology. 2008;109(6):989-97.
10. Upile T, Jerjes W, Mahil J, et al. Blood product transfusion and cancer prognosis. Clin Adv Hematol Oncol. 2009;7(10):656-61.
11. Kozek-Langenecker SA, Ahmed AB, Afshari A, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol. 2017;34(6):332-95. DOI:10.1097/EJA.0000000000000630
12. Tran DH, Wong GT, Chee YE, Irwin MG. Effectiveness and safety of erythropoiesis-stimulating agent use in the perioperative period. Expert Opin Biol Ther. 2014;14(1):51-61.
13. Popovsky MA, Devine PA, Taswell HF. Intraoperative autologous transfusion. Mayo Clin Proc. 1985;60(2):125-34.
14. Buth J, Raines JK, Kolodny GM, Darling RC. Effect of intraoperative autotransfusion on red cell mass and red cell survival. Surg Forum. 1975;26:276‑8.
15. Ray JM, Flynn JC, Bierman AH. Erythrocyte survival following intraoperative autotransfusion in spinal surgery: an in vivo comparative study and 5-year update. Spine (Phila Pa 1976). 1986;11(9):879-82.
16. Homann B, Zenner HP, Schauber J, Ackermann R. Tumor cells carried through autotransfusion. Are these cells still malignant? Acta Anaesthesiol Belg. 1984;35(Suppl.):51-9.
17. Miller GV, Ramsden CW, Primrose JN. Autologous transfusion: an alternative to transfusion with banked blood during surgery for cancer. Br J Surg. 1991;78(6):713‑5.
18. Klezl P, Pospisilova E, Kolostova K, et al. Detection of Circulating Tumor Cells in Renal Cell Carcinoma: Disease Stage Correlation and Molecular Characterization. J Clin Med. 2020;9(5):1372.
19. Oefelein MG, Kaul K, Herz B, et al. Molecular detection of prostate epithelial cells from the surgical field and peripheral circulation during radical prostatectomy. J Urol. 1996;155(1):238-42.
20. Weiss L. Metastatic inefficiency: causes and consequences. Cancer Rev. 1986;3:1-24.
21. Frietsch T, Steinbicker AU, Horn A, et al. Safety of Intraoperative Cell Salvage in Cancer Surgery: An Updated Meta-Analysis of the Current Literature. Transfus Med Hemother. 2022;49(3):143-57.
22. Moskowitz DM, Perelman SI, Cousineau KM, et al. Multidisciplinary management of a Jehovah’s Witness patient for the removal of a renal cell carcinoma extending into the right atrium. Can J Anaesth. 2002;49(4):402-8.
23. Casey RG, Raheem OA, Elmusharaf E, et al. Renal cell carcinoma with IVC and atrial thrombus: a single centre’s 10 year surgical experience. Surgeon. 2013;11(6):295-9.
24. Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology. Arch Surg. 1986;121(11):1326-9.
25. Lyon TD, Ferroni MC, Turner RM, et al. Shortterm outcomes of intraoperative cell saver transfusion during open partial nephrectomy. Urology. 2015;86(6):1153-8.
26. Zhang X, Guo X, Zong Y. CTCs detection from intraoperative salvaged blood in RCC–IVC thrombus patients by negative enrichment and iFISH identification: a preliminary study. BMC Urol. 2021;21(1):89.
27. Carless PA, Henry DA, Moxey AJ, et al. Cell salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2010;3:CD001888.
28. Domen RE. Adverse reactions associated with autologous blood transfusion: evaluation and incidence at a large academic hospital. Transfusion. 1998;38(3):296‑300.
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ГБУЗ «Городская клиническая онкологическая больница №1» Департамента здравоохранения г. Москвы, Москва, Россия;
3 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
4 АНО «Научно-образовательный центр “Евразийская онкологическая программа” ЕАФО», Москва, Россия
*mivolkova6@gmail.com
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Maria I. Volkova*1,2, Pavel I. Feoktistov3, Adilet K. Begaliev2, Alexandr R. Shin3, Vsevolod B. Matveev3, Aleksey O. Prikhodchenko4
1 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
2 City Clinical Oncology Hospital №1, Moscow, Russia;
3 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
4 Scientific and Educational Center “Eurasian Cancer Program EAFO”, Moscow, Russia
*mivolkova6@gmail.com