POSTRADIATION CHANGES IN THE ORAL MUCOSA. ORAL MUCOSITIS

The authors of the article conducted a descriptive synthesis of the literature to determine the etiology, pathogenesis, treatment and prevention of oral mucositis, as well as to assess the impact of post-radiation mucositis on the quality of life of an oncological patient. The search for articles was carried out in three main Russian and foreign databases in the field of health and social sciences: eLibrary, CyberLeninka, PubMed.

Oral mucositis is an inflammation of the mucosa and submucosa of the oral cavity, often a complication of radiation therapy. Mucositis is a pressing problem of the present time, requiring an integrated approach to timely diagnosis and treatment. The pathology has a negative impact on the patient's condition, capturing social, economic, medical and psychological aspects. Of particular interest is the study of histological factors that have a certain significance in the development of oral mucositis: mast cells (MC), VEGF factor, CD-68 and CD-163 macrophages. The work artificially reproduced oral mucositis, presented photos of sections of the oral mucosa of the control group of rats. It was found that MC are an important factor in triggering the inflammatory process, and also affect the angiogenesis process. Immunohistochemical identification of VEGF in the oral mucosa of experimental rats with oral mucositis was carried out and significant expression of VEGF in newly formed vessels of the microcirculatory bed was shown. It was revealed that the number of CD68 and CD-163 positive macrophages correlates with a poor outcome of malignant disease in patients. Thus, clinical manifestations depend on the risk factors of a particular patient, the characteristics of the course of the tumor disease and radiation therapy. The approach to treatment causes certain difficulties for doctors, symptomatic therapy, laser radiation and experimental therapy are used. Therefore, the study of histological factors on a biomodel of radiation-induced oral mucositis will expand our understanding of the pathogenesis of the disease and contribute to the search for new drugs for the treatment and prevention of the pathology under study.

1. A.D. Kaprin, Starinskiy V.V., Shahzadova A.O. Sostojanie onkologicheskoj pomoshhi naseleniju Rossii v 2023 godu (The state of oncological care for the population of Russia in 2023). Moskva: MNIOI im. P.A. Gercena – filial FGBU «NMIC radiologii» Minzdrava Rossii, 2024:262. (in Russ)

2. Moshurov I. P., Olshansky M. S., Shishkina V. V. [et al.] Correlation of quantitative indicators of tissue tryptase and chymase with morphological and clinical characteristics of oropharyngeal cancer. Centennial anniversary of the Voronezh oncology service: Collection of papers of the scientific and practical conference, Voronezh, December 12, 2024.Voronezh: Voronezh State Medical University named after N. N. Burdenko.2024; 239-241. (in Russ)

3. Savenok E. V., Panov E. D., Olshansky M. S. [et al.] The place of intra-arterial chemotherapy (IAC) in the complex treatment of locally advanced tongue cancer. Research and practice in medicine.2018;(5):188. (in Russ)

4. Eremina A. O., Zaderenko I. A., Ivanov S. Yu. [et al.] Oral mucositis in patients with oncological pathology of the oropharyngeal region: a literature review. Head and neck tumors.2020;(10):72-80. (in Russ) DOI 10.17650/2222-1468-2020-10-3-72-80.

5. Kumar S. Radiation Mucositis. In: Gabor Racz, Pain management - current issues and opinions. InTech: Gabor Racz.2012;469-82. (in Engl) doi: 10.4103/0973-1075.58452

6. Kazeko, L. A., Degtyareva M. I. Oral mucositis: modern aspects. Healthcare (Minsk).2019;(4):12-19. (in Russ)

7. Eremina A. O., Zaderenko I. A., Ivanov S. Yu. [et al.] Oral mucositis in patients with oncological pathology of the oropharyngeal region: a review of the literature. Tumors of the head and neck.2020;(10):72-80. (in Russ) DOI 10.17650/2222-1468-2020-10-3-72-80

8. Sarzhevsky V. O., E. G. Smirnova Features of pathogenesis, clinical manifestations, prevention and treatment of mucositis in cancer patients. Bulletin of the National Medical and Surgical Center named after. N.I. Pirogov.2012;(7):123-128. (in Russ)

9. Gvozdikova E. N., Avanesov A. M. Study of genetic factors associated with the prognosis of the development of oral mucositis in patients with squamous cell carcinoma of the oropharyngeal region receiving antitumor treatment. Bulletin of the Russian Scientific Center of Radioradiology. 2017;(17):6. (in Russ)

10. Popruzhenko T. V., Uglova T. A., Boris S. P. Chemotherapeutic oral mucositis: current state of the problem. Modern dentistry.2011;(2):14-20. (in Russ)

11. Radzhabova Z. A., Kotov M. A., Sereda O. A. [et al.] Oral mucositis as a complication of antitumor treatment in patients with locally advanced head and neck cancer: a literature review. Issues of oncology.2021;(67):606-613. (in Russ) DOI 10.37469/0507-3758-2021- 67-5-606-613

12. Parkhomenko L. B. Modern concepts of the development of mucositis during irradiation of head and neck cancer. Medical news. 2019;(10):15-18. (in Russ)

13. Gassan, M. V., Sedinina A. S. Mukozit polosti rta, vyzvannyj protivoopuholevoj terapiej Innovacionnoe razvitie sovremennoj nauki (Oral mucositis caused by antitumor therapy. Innovative development of modern science): Sbornik nauchnyh trudov po materialam XLII Mezhdunarodnoj nauchno-prakticheskoj konferencii, Anapa, 10 dekabrja 2021 goda. Anapa: OOO «Nauchno-issledovatel'skij centr jekonomicheskih i social'nyh processov» v Juzhnom Federal'nom okruge, 2021: 212-216. (in Russ)

14. Elad S, Cheng KKF, Lalla RV, Yarom N [et al.] Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020;126(19):4423-4431. (in Engl) doi: 10.1002/cncr.33100.

15. Chen C, Zhang Q, Yu W, Chang B, Le AD. Oral Mucositis: An Update on Innate Immunity and New Interventional Targets. J Dent Res.2020;99(10):1122-1130. (in Engl) doi: 10.1177/0022034520925421.

16. Tsibulkina, V. N., Tsibulkin N. A. Mast cell as a multifunctional element of the immune system. Allergology and immunology in pediatrics.2017;2(49):4-11. (in Russ)

17. Pulito C, Cristaudo A, Porta C, Zapperi S, Blandino G, Morrone A, Strano S. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res.2020;39(1):210. (in Engll) doi: 10.1186/s13046-020-01715-7.

18. Faustino-Rocha AI, Gama A, Neuparth MJ, Oliveira PA, Ferreira R, Ginja M. Mast Cells in Mammary Carcinogenesis: Host or Tumor Supporters? Anticancer Res.2017;37(3):1013-1021. (in Engl) doi:10.21873/anticanres.11411.)

19. Welti J, Loges S, Dimmeler S, Carmeliet P. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest.2013; 123(8):3190-200. (in Engl) doi: 10.1172/JCI70212.

20. Shatokhina E. A., Logacheva N. S., Konova Z. V., Kuzmina L. A. Oral mucositis as a complication of antitumor therapy: modern concepts of pathogenesis, prevention and approaches to treatment. Effective pharmacotherapy.2023;(19):92-100. (in Russ)

21. Fujii N, Shomori K, Shiomi T, Nakabayashi M, Takeda C, Ryoke K, Ito H. Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. J Oral Pathol Med.2012;41(6):444-51. (in Engl) doi: 10.1111/j.1600-0714.2012.01127.x.

22. Moshurov I. P., Korotkikh N. V., Shishkina V. V., Semenov D. A. Development of a biomodel of radiation-induced oral mucositis and evaluation of the effectiveness of sodium deoxyribonucleate in the treatment of radiation mucositis. Centennial anniversary of the Voronezh oncology service: Collection of papers of the scientific and practical conference, Voronezh, December 12, 2024. Voronezh: Voronezh State Medical University named after N. N. Burdenko.2024;232-238. (in Russ)

23. Tyrsina E. G., Nikulitsky S. I. The role of the regulatory VEGF/VEGF-R1 system in tumor angiogenesis (literature review). Oncogynecology.2015;(4):4-12. (in Russ)

24. Popykhova, E. B. The role of VEGF in the process of angiogenesis in health and pathology. Traumatology, orthopedics and neurosurgery: interdisciplinary aspects: collection of scientific papers. Research Institute of Traumatology, Orthopedics and Neurosurgery of the Federal State Budgetary Educational Institution of Higher Education Saratov State Medical University named after V.I. Razumovsky, Ministry of Health of the Russian Federation Association of Traumatologists and Orthopedists of Russia Association of Vertebrologists of Russia. Saratov: OOO «Amirit».2019;104-107. (in Russ)

25. Yartseva A. A., Stepanov A. V., Grebenyuk A. N. [et al.] The state of the oral microbiocenosis of experimental animals exposed to the combined effects of damaging factors of chemoradiotherapy. Bulletin of the Russian Military Medical Academy.2014;1(45):105-109. (in Russ)

26. Avanesov A. M., Gvozdikova E. N., Nguyen Z. H. [et al.] Assessment of the quality of life of cancer patients as an indicator of the intensity of clinical manifestations and an indicator of the effectiveness of treatment of oral mucositis. Bulletin of the Russian Scientific Center of Roentgenology and Radiology.2020;(20):1-19. (in Russ)

27. Avanesov A.M. Clinical and organizational prerequisites for the occurrence of complications in the oral cavity in patients receiving radiation and chemoradiotherapy. Head&Neck Russian Journal. Application. Collection of abstracts.2017;(2):94. (in Russ)

28. Semiglazova T. Yu., Belyak N. P., Vladimirova L. Yu. [et al.] Practical recommendations for the treatment and prevention of mucositis. Malignant tumors.2021;(11):224-232. (in Russ) DOI 10.18027/2224-5057-2021-11-3s2-51)

29. Bernatsky A. S., Vagaytseva M. V., Demin E. V. [et al.] Oncopsychology. A guide for oncologists and medical psychologists: a guide. St. Petersburg: Questions of oncology.2017:350. (in Russ)

30. Alymov Yu. V., Mudunov A. M., Aliyeva S. B. [et al.] The role of hyaluronic acid preparations in the prevention and treatment of radiation mucositis of the oral cavity and oropharynx. Head and Neck Tumors.2019;(9):29-37. (in Russ) DOI 10.17650/2222-1468-2019-9-3-29-3

31. Dzherelei A. A., Romanenko I. G., Kryuchkov D. Yu. [et al.] Features of the course of oral mucositis in patients with a harmonious psychological reaction against the background of squamous cell carcinoma of the oral mucosa. Crimean therapeutic journal.2022;(1):50-52. (in Russ)

32. Sedova E. S., Yusupov V. I., Vorobyova N. N. [et al.] Efficiency of low-intensity laser radiation for the prevention and treatment of radiation-induced mucositis of the oral cavity and pharynx. Siberian journal of oncology.2018;(17):11-17. (in Russ)

33. Makedonova Yu. A., Mikhalchenko D. V., Afanasyeva O. Yu. [et al.] Methodology for the use of ozone therapy for the treatment of peri-implantation mucositis. Medical alphabet.2021;(2):80-84. (in Russ) DOI 10.33667/2078-5631-2021-1-86-84

34. Degtyareva, M. I. New in the treatment of oral mucositis. Modern technologies in medical education: Proceedings of the international scientific and practical conference dedicated to the 100th anniversary of the Belarusian State Medical University, Minsk, November 01– 05, 2021. Minsk: BSMU.2021;1170-1173. (in Russ)

35. Daraushe H. M., Gvozdikova E. N., Kandakova E. Yu. [et al.] Modern approaches to the treatment of chemotherapeutic oral mucositis. Bulletin of the Russian Scientific Center of Roentgenology and Radiology.2021;(21):50-71. (in Russ)

36. Avanesov A. M., Gvozdikova E. N. Prognostic factors determining the clinical course of oral mucositis in patients with squamous cell carcinoma of the oropharyngeal region. Bulletin of the Peoples' Friendship University of Russia. Series: Medicine.2018;(22):22-28. (in Russ) DOI 10.22363/2313-0245-2018-22-1-22-28.

37. Villa A, Sonis ST. An update on pharmacotherapies in active development for the management of cancer regimen-associated oral mucositis. Expert Opin Pharmacother.2020;21(5):541-548. (in Engl) doi: 10.1080/14656566.2020.1718652.

38. Thompson JA, Schneider BJ, Brahmer J, Zaid MA [et al.] NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024. J Natl Compr Canc Netw.2024;22(9):582-592. (in Engl) doi: 10.6004/jnccn.2024.0057

39. Avanesov A. M., Gvozdikova E. N., Tarasova T. V. [et al.] The Impact of the Quality of Individual Oral Hygiene on the Severity of Post-Radiation Mucositis in Patients with Squamous Cell Carcinoma of the Oropharyngeal Region / // South-Russian Journal of Oncology.2020;1(2):6-12. (in Engl) DOI 10.37748/2687-0533-2020-1-2-1

40. Degtyareva M. I., Kazeko L. A., Kolyadich J. V. [et al.] Clinical course of oral mucositis during radiation therapy. Healthcare (Minsk).2022;1(898):48-55. (in Russ)