ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА ПРЕДОПЕРАЦИОННОГО АНЕМИЧЕСКОГО СИНДРОМА У БОЛЬНЫХ РАКОМ ПРЯМОЙ КИШКИ

Аннотация

Проведено исследование основных показателей красной крови (RBC, HGB, MCV, MCH, RET-HE) и концентрации ферритина (ФР), гепсидина-25 (ГП-25), ИЛ-6, растворимых рецепторов трансферрина (рРТФ), эритропоэтина (ЭПО) у 41 больного раком прямой кишки (РПК) до операции. Контрольная группа состояла из 50 человек без онкопатологии. Целью работы явилась ранняя и дифференциальная диагностика анемического синдрома (АС). АС выявили у 58,5% больных РПК. Диагностированы три варианта анемического синдрома АС: ЖДА, ЖДЭ и функциональный дефицит железа (ФДЖ). Для всех вариантов АС был характерен микроцитоз и гипохромия эритроцитов и ретикулоцитов, что свидетельствовало о железодефицитном эритропоэзе. Достоверное различие было выявлено в показателях ФР, ГП-25, ИЛ-6, HGB, MCV, MCH, RET-HE. У больных с ФДЖ значения ФР, ГП-25, ИЛ-6 были статистически значимо выше, а уровни HGB, MCV, MCH, RET-HE ниже, чем у больных с ЖДА и ЖДЭ (p<0,01). ФДЖ встречался чаще у больных с III-IV стадией РПК. Дефицит ЭПО был выявлен во всех вариантах АС. Самая низкая продукция ЭПО отмечена у больных с III-IV стадией РПК и с ФДЖ. Полученные данные по исследованию ГП25 в комплексе с ИЛ-6 у больных с ФДЖ свидетельствуют о необходимости дальнейшего уточнения их роли в дифференциальной диагностике и оценке адекватности лечения больных раком прямой кишки с АС.

Annotation

A study was conducted of the main indicators of red blood (RBC, HGB, MCV, MCH, RET-HE) and the concentration of ferritin (FR), hepcidin-25 (GP-25), IL-6, soluble transferrin receptors (sRTF), erythropoietin (EPO) in 41 patient with rectal cancer (RC) before surgery. The control group consisted of 50 people without cancer. The purpose of the work was early and differential diagnosis of anemic syndrome (AS). AS was detected in 58.5% of patients with RC. Three variants of anemic AS syndrome have been diagnosed: IDA, IDE and functional iron deficiency (FID). All variants of AS were characterized by microcytosis and hypochromia of erythrocytes and reticulocytes, which indicated iron deficiency erythropoiesis. A significant difference was found in the parameters of RF, GP-25, IL-6, HGB, MCV, MCH, RET-HE. In patients with FID, the values of FR, GP-25, IL-6 were significantly higher, and the levels of HGB, MCV, MCH, RET-HE were lower than in patients with IDA and IDE (p<0.01). FID was more common in patients with stage III-IV RC. EPO deficiency was identified in all variants of AS. The lowest EPO production was observed in patients with stage III-IV RC and FID. The data obtained on the study of GP-25 in combination with IL-6 in patients with FID indicate the need for further clarification of their role in the differential diagnosis and assessment of the adequacy of treatment of patients with rectal cancer with AS. Key words: rectal cancer; anemia; functional iron deficiency; ferritin; hepcidin 25; interleukin-6; erythropoietin

Об авторах

Список литературы

1. Natalucci V., Virgili E., Calcagnoli F., Valli G., Agostini D., Zeppa S.D. et al. Cancer related anemia: an integrated multitarget approach and lifestyle interventions. Nutrients. 2021; 13(2): 482. DOI: 10.3390/nu13020482.
2. Deng Yu, Wen M., Zhang J. Preoperative anemia and long-term survival in patients undergoing colorectal cancer surgery: a retrospective cohort study. World J. Surg. Onc. 2023; 21: 122. DOI: 10.1186/s12957-023-03005-w.
3. Warner M.A., Shore-Lesserson L., Shander A., Patel S.I., Perelman S.I., Gwynn N.R. Perioperative anemia: prevention, diagnosis and management across the spectrum of perioperative care. Anesthesiology. 2020; 130:1364–72.
4. Sakhin V.T., Madzhanova E.R., Kryukov E.V. Kazakov S.P., Rukavitsyn O.A. Anemia of chronic diseases: Features of pathogenesis and possibilities of therapeutic correction (review of the literature and the results of our research). Onkogematologiya. 2018; 13(1): 45–53. (in Russian)
5. Smirnov S.Yu, Gutkovskaya E.A., Xodasevich V.M., Chekun O.V., Suboch E.I., Portyanko A.S. et al. Molecular genetic markers of sensitivity to therapy in colorectal cancer. Molekulyarnaya i prikladnaya genetika. 2020; 29: 86–96 (in Russian)
6. Xagazheeva M.N., Snegovoy A.V., Blindar` V.N., Ryabchikov D.A.,Dobrovol`skaya M.M., Kononenko I.B. et al. The role of hepcidin 25 in the development of anemic syndrome associated with malignant diseases. Rossiyskiy bioterapevticheskiy zhurnal. 2020; 19(4): 29–34. DOI: 10.17650/1726-9784-2020-19-4-29-34. (in Russian)
7. Wang J., Liu W., Lee J.K., Mingy Li, Benyi Li, Runzhi Zhu et al. Hepcidin downregulation correlates with disease aggressiveness and immune infiltration in liver cancer. Frontal. oncology. 2021; 11: 714756. DOI: 10.3389/fonc.2021.714756.
8. Aapro M., Beguin Y., Bokemeyer C., Dicato M., Gascón P., Glaspy J. et al. Management of anemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines. Annals of Oncology. 2018; 29(4):96-110. DOI: 10.1093/annonc/mdx758.
9. Bruns E.R.D.M.N., Borstlap V.A., van Duyvendijk P., van der Zaag-Lunen H.J., Burkens Ch.J., Munster B.C. et al. The association of preoperative anemia and the postoperative course and oncological outcome in patients undergoing rectal cancer surgery: a multicenter snapshot study. Colorectal. Dis. 2019; 62 (7):823-31. DOI: 10.1097/DCR.0000000000001360.
10. Sasu B.J., Cooke K.S., Arvedson T.L., Pleva S., Ellison A.R, Sheng J. et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010; 115: 3616-24.
11. Nemeth E., Ganz T. Hepcidin-ferroportin interaction controls systemic iron homeostasis. Int. J. Mol. Sci. 2021; 22:6493. DOI: 10.3390/ijms22126493.
12. World Medical Association, Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013; 310(20): 2191-4. PMID 24141714. DOI: 10.1001/jama.2013.281053.
13. Andersen A. B., Bonn T.K., Bader J., Jung G., Ganz T., Nemeth E. et. al. Effect of altitude and recombinant human erythropoietin on iron metabolism: a randomized controlled trial. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2021; 321(2): R152-R161. DOI: 10.1152/ajpregu.00070.2021. Epub 2021 June 23.
14. Bohlius J., Bohlke K., Castelli R., Dzhulbegovic B., Lustberg M.B., Martino M. et al. Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update. Blood Adv. 2019; 3: 1197–1210.
15. Ashby D.R., Gale D.P., Busbridge M., Murphy K. G., Duncan N. D., Cairns T.D. et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica. 2010; 95(3): 505-8.
16. Sasaki U., Noguchi-Sasaki M., Yasuno H., Yorozu K., Shimonaka Y. Stimulation with erythropoietin reduces the expression of hepcidin due to the hematopoietic activity of bone marrow cells in mice. Int. J. Hematol. 2012; 96(6): 692-700.
17. Vyoral D., Petrak J. Therapeutic potential of hepcidin — the master regulator of iron metabolism. Pharmacological research. 2017; 115:242–54. DOI: 10.1016/j.phrs.2016.11.010.
18. Blindar` V.N., Zubrikhina G.N., Davy`dova T.V., Dobrovol`skaya M.M. Features of the regulation of hepcidin and ferroportin in cancer patients (literature review). Rossiyskiy bioterapevticheskiy zhurnal. 2023; 22(3):10-8. DOI: 10.17650/1726‑9784‑2023‑22‑3‑10‑18. (in Russian)

Ключевые слова