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Experimental and Clinical Gastroenterology

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Colorectal and Stomach Cancer, a New Look at the Features of Morphogenesis

https://doi.org/10.31146/1682-8658-ecg-235-3-13-28

Abstract

Purpose of the study: to determine the reasons for the increase in the incidence of colon and stomach cancer, as well as the insufficient effectiveness of colon cancer screening and prevention programs. Material and methods of research: clinical and endoscopic, most often annual studies of the colon in 4134 patients over a 15-year period with morphological assessment of the changes detected (more than 11,000 preparations); the method of esophagogastroduodenoscopy with biopsy of gastric tumors (113 studies); special methods of morphological studies, including electron microscopy, detection of hybrid cells; methods of vital chromo- and colonomicroscopy, including for prospective study of the structure of the mucous membrane in the zone of probable development of cancerous tumors during subsequent observations; the method of gastromicroscopy; a laboratory method for studying the concentration of carcinoembryonic antigen (CEA) in homogenates of tissues of the mucous membrane and cancerous tumors. Research results: annual dynamic observations of patients for 15 years showed that development of sporadic cancer in the colon occurred in 3.4% of patients. In most of them (83.8%) cancer tumors appeared during annual intervals between observations without any visible connection with previous adenomas; we stated the absence of practical possibility to predict timing and localization of development of cancer tumors in them. Tumors with high growth rates appeared on the border between the epithelial surface with signs of moderate diffuse hyperplasia (DH) and the epithelial surface of small adenomas (A) with moderate dysplasia of gland epithelium. It was established that in cases of rapid development of cancer adenoma and carcinoma are not consecutive stages of malignancy, but on the contrary - a synchronous process. This type of cancer tumors develops as a result of fusion (hybridization) of cells of hyperplastic epithelium and epithelium of adenomas. A more pronounced increase in the concentration of CEA in tumors compared to the surrounding mucous membrane confirmed the embryonic origin of tumors of this type. Cells with morphological features of hybrids were also found in gastric cancer tumors. Conclusion: A pathoembryonic theory is presented with a complete cycle of morphological changes, including the diversity of the structure of the surface epithelium in the colon and the discovery of hybridization of cells from adjacent differently structured epithelia as a biological mechanism leading to the initiation of cancer with high growth rates (similar changes were found in gastric tumors). It is also shown that tumors with slow growth rates in the colon are formed mainly from previous adenomas as they recur and the degree of dysplasia of the glandular epithelium increases in them in accordance with the generally accepted views on the process of carcinogenesis in the colon. Known promoters of hybridization of epithelial somatic cells include polyethylene glycol, which is widely used in medicine, as well as in the food industry; there is reason to believe that a significant part of such substances (fusogens) have not been identified to date. A number of signs suggest that hybrid cells also play a significant role in the metastatic process.

About the Authors

S. L. Khankin
LLC "Professional"
Russian Federation


V. S. Rubtsov
LLC "Med. Di Center
Russian Federation


A. M. Napsheva
Saratov State Medical University named after V.I. Razumovsky (Razumovsky University)
Russian Federation


References

1. Vogelstein B., Fearon E.R., Hamilton S.R. et al. Genetic alterations during colorectal-tumor development. New England Journal of Medicine. 1988;319(9):525-532. doi: 10.1056/NEJM198809013190901.

2. Hu B., El Hajj N., Sittler S. et al. Gastric cancer: Classification, histology and application of molecular pathology. Journal of Gastrointestinal Oncology. 2012;3(3):251-261. doi: 10.3978/j.issn.2078-6891.2012.021.

3. Sidorova A.N., Klimenko V.N., Sherbakov A.M., Tkachenko O.B. Morden tactic in diagnosis and treatment of early colon cancer (review of literature). The Scientific Notes of Pavlov University. 2020;27(4):28-37. (In Russ.) doi: 10.24884/1607-4181-2020-27-4-28-37.@@ Сидорова А.Н., Клименко В.Н., Щербаков А.М., Ткаченко О.Б. Современная тактика в диагностике и лечении раннего рака толстой кишки (обзор литературы). Ученые записки СПбГМУ имени академика ИП. Павлова. 2020;27(4):28-37. doi: 10.24884/1607-4181-2020-27-4-28-37.

4. Uedo N., Takeuchi Y., Ishihara R. Endoscopic management of early gastric cancer: endoscopic mucosal resection or endoscopic submucosal dissection: data from a Japanese high-volume center and literature review. Annalis of Gastroenterology. 2012;25(4):281-290. doi:10.13140/RG.2.2.25814.09287.

5. Strekalovsky V.P., Khankin S.L., Kuznetsov A.N. Development of metachronous tumors of the colon. Clinical medicine. 1990;68(1):95-100. (In Russ.)@@ Стрекаловский В.П., Ханкин С.Л., Кузнецов А.Н. О развитии метахронных раковых опухолей толстой кишки. Клиническая медицина. 1990;68(1): 95-100.

6. Besova N.S., Kalinin A.E., Nered S.N. et al. Gastric cancer: Russian clinical guidelines. Journal of Modern Oncology. 2021;23(4):541-571. (In Russ.) doi: 10.26442/18151434.2021.4.201239.@@ Бесова Н.С., Калинин А.Е., Неред С.Н. и др. Рак желудка. Клинические рекомендации. Современная онкология. 2021;23(4):541-571. doi: 10.26442/18151434.2021.4.201239.

7. Khankin S.L. Endomicroscopic assessment of regulation of hyperplastic and dysplastic processes in the colon mucosa. Scientific conference dedicated to the 160th anniversary of I.M. Sechenov’s birthday, May 22-24. Odessa, 1989:68-69. (In Russ.)@@ Ханкин С.Л. Эндомикроскопическая оценка регуляции гиперпластических и диспластических процессов в слизистой оболочке толстой кишки. Одесская областная научная конференция, посвященная 160-летию со дня рождения И.М. Сеченова: 22-24 мая 1989 г.: тезисы докладов. Одесса, 1989. С. 68-69.

8. Khankin S.L. [Clinical and endoscopic evaluation of appearance and development of epithelial neoplasms in the large bowel]. Diss… Med Sciences. Moscow, 1992, 325 p. (In Russ.)@@ Ханкин С.Л. Клинико-эндоскопическая оценка возникновения и развития эпителиальных новообразований толстой кишки: диссертация … доктора медицинских наук: 14.00.14. Московский научно-исследовательский онкологический институт. Москва, 1992. 325 с.

9. Morson B.S., Muto T., Bussey H.J.R. The evaluation of cancer of the colon and rectum. Cancer. 1975;36:2251-2270. doi: 10.1002/cncr.2820360944.

10. Morson B. The Polyp-Cancer Sequence in the Large Bowel. Proceedings of the Royal Society of Medicine. 1974;67(6):451-457. doi: 10.1177/00359157740676P115.

11. Hankin S.L. The mechanism of rapid development of epithelial tumors using the example of colorectal cancer. Filin’s Clinical endoscopy. 2023;63(2):40-45. (In Russ.) doi: 10.31146/2415-7813-endo-63-2-40-45.@@ Ханкин С.Л. Механизм быстрого развития эпителиальных опухолей на примере колоректального рака. Клиническая эндоскопия. 2023;63(2):40-45. doi: 10.31146/2415-7813-endo-63-2-40-45.

12. Khankin S.L. Endomicroscopic evaluation of interactions between focal and diffuse changes in the colonic mucosa. Proceedings of the Symposium on sedation and monitoring in endoscopy at the World congresses of gastroenterology, Sydney, Australia, 30 Aug. 1990: An offic. publ. of the 1990 / Ed. by S. Benjamin. Oslo: Universitetsforl, 1990, pd. 759.

13. Khankin S.L. Developmental characteristics of sporadic colonic cancer according to data of endoscopic and morphologic investigations. MosEndo: account YouTube. Session no. 177. 02.03.2022. (in Russ.) Available at: https://rutube.ru/video/a18a13836a4b2de597a953372a2956f2/(Accessed 11 Aprl 2025)@@ Ханкин С.Л. Особенности развития спорадического рака толстой кишки по данным эндоскопических и морфологических исследований. МосЭндо: аккаунт на YouTube. Заседание № 177. 02.03.2022. доступно на: https://rutube.ru/video/a18a13836a4b2de597a953372a2956f2/(дата обращения 11.04.2025).

14. Khankin S.L. The mechanism of rapid pace of growth of epithelial tumors using the example of colon cancer. MosEndo: account YouTube. Session no. 197. 24.05.2023. (In Russ.) Available at: https://rutube.ru/video/16aa41400ac1a9686faac0600da88060/(Accessed: 11.04.2025).@@ Ханкин С.Л. Механизм быстрого развития эпителиальных опухолей на примере колоректального рака. МосЭндо: аккаунт на YouTube. Заседание № 197. 24.05.2023. Доступно на: https://rutube.ru/video/16aa41400ac1a9686faac0600da88060/(дата обращения 11.04.2025).

15. Khankin S.L., Rubzov V.S., Fedotov E.A., Napsheva A.M. Colonic cancer with rapid pace of growth. MosEndo: account YouTube. Session no. 210. 11.09.2024. (In Russ.) Available at: https://rutube.ru/video/6881435d38ae8702c0c875f5467f7be2/(Accessed: 11.04.2025).@@ Ханкин С.Л., Рубцов В.С., Федотов Э.А., Напшева А.М. Рак толстой кишки с быстрыми темпами роста. МосЭндо: аккаунт на YouTube. Заседание № 210. 11.09.2024. Доступно на: https://rutube.ru/video/6881435d38ae8702c0c875f5467f7be2/(дата обращения 11.04.2025).

16. Khankin S.L., Kapuller L.L., Kuznetsov A.N. The World Congress of Gastroenterology: october 2-7. Los Angeles, California, 1994, abstr. 823.

17. Khankin S.L., Strekalovsky V.P. Principles of interpretation of colonomicroscopy with great magnification. Abstract Book, World Congress: Gastroenterology (Omge) 8-th Congress, Digestive Endoscopy (Omed) 6th Congress, Colo-Proctology 3rd Congress: September 7-12. Sao Paulo, Brazil, 1986, abstr. 1967.

18. Khankin S.L., Beljaev M.V., Gorbeshko T.P. Contact endomicroscopy of the large bowel with great magnification. Clinical medicine. 1984;62(1):126-130. (in Russ.)@@ Ханкин С.Л., Беляев М.В., Горбешко Т.П. Контактная эндомикроскопия толстой кишки с большим увеличением. Клиническая медицина. 1984;62(1):126-130.

19. Khankin S.L, Beliaev M.V, Gorbeshko T.P. Peculiarities of vital staining of tumors and hyperplastic changes in the colonic mucosa. Clinical medicine. 1983;61(8):88-91. (in Russ.)@@ Ханкин С.Л., Беляев М.В., Горбешко Т.П. Об особенностях витальной окраски опухолей и гиперпластических изменениях в слизистой оболочке толстой кишки. Клиническая медицина. 1983;61(8):88-91.

20. Strekalovsky V.P, Khankin S.L, Gorbeshko T.P, Beliaev M.V. Endoscopic microscopy of the colon. Endoscopy. 1984;16(5):179-181. doi: 10.1055/s-2007-1018574.

21. Strekalovsky V.P, Khankin S.L, Kapuller L.L. Microendoscopic features of the surface epithelium in patients with colonic tumors. Endoscopy. 1989;21(2):75-78. doi: 10.1055/s-2007-1012904.

22. Saljamon L.S. Cancer and disfunction of sell. Leningrad. Nauka, 1974. 320 p. (in Russ.)@@ Салямон Л.С. Рак и дисфункция клетки. Ленинград: Наука, 1974. 320 с.

23. Shabad L.M. Evolution of concepts of blastomogenesis. Moscow. Medicine, 1979: 270 p. (in Russ.)@@ Шабад Л.М. Эволюция концепций бластомогенеза. Москва: Медицина, 1979. 270 с.

24. Ehrenpreis Ya.G. Embrionic properties of tumor cells: facts and hypotheses. Experimental oncology. 1982;4(6):13-19. (in Russ.)@@ Эренпрейс Я.Г. Эмбриональные свойства опухолевых клеток: факты и гипотезы. Экспериментальная онкология. 1982;4(6):13-19.

25. Ephrussi B, Davidson R.L, Weiss M.C., et al. Malignancy of somatic cell hybrids. Nature. 1969;224(5226):1314-1316. doi: 10.1038/2241314a0.

26. Efrussi B. Hybridization of somatic cells. Princeton: N.J., Princeton University Press, 1972. 175 p.

27. Hass R., von der Ohe J., Dittmar T. Hybrid Formation and Fusion of Cancer Cells In Vitro and In Vivo. Cancers (Basel). 2021;13(17):4496. doi: 10.3390/cancers13174496.

28. Kaigorodova E.V., Zavaruev I.S., Chernyshova A.L., Grishchenko M. Yu. Prognostic significance of atypical/hybrid forms of EpCAM+CD45+ cells in the blood of patients with endometrial cancer. Opukholi zhenskoy reproduktivnoy systemy = Tumors of female reproductive system. 2023;19(2):104-108. (In Russ.) doi: 10.17650/1994-4098-2023-19-2-104-108.@@ Кайгородова Е.В., Заваруев И.С., Чернышова А.Л., Грищенко М.Ю. Прогностическая значимость атипичных/гибридных форм клеток ЕpCAM+CD45+ в крови у больных раком эндометрия. Опухоли женской репродуктивной системы. 2023;19(2):104-108. doi: 10.17650/1994-4098-2023-19-2-104-108.

29. Zhou X., Merchak K., Lee W. et al. Cell Fusion Connects Oncogenesis with Tumor Evolution. American Journal of Pathology. 2015;185(7):2049-2060. doi: 10.1016/j.ajpath.2015.03.014.

30. Stephens P.J., Greenman C.D., Fu B. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27-40. doi: 10.1016/j.cell.2010.11.055.

31. Strekalovsky V.P., Khankin S.L., Zacharjan V.G. Endoscopic microscopy of the stomach. Terapevticheskii Arkhiv. 1983; 55(21):75-78. (in Russ.)@@ Стрекаловский В.П., Ханкин С.Д., Захарьян В.Г. Эндоскопическая микроскопия желудка. Терапевтический архив. 1983;55(2):76-78.

32. Strekalovsky V.P. Results of endoscopic removal of villous tumors of the colon. Endoscopy. 1983;15(2):49-52. doi: 10.1055/s-2007-1018609.

33. Veselov V.V. [Endoscopic treatment of patients with large and giant adenomas of the large bowel]. Diss… Med. Sciences. Moscow, 1997. 135 p. (in Russ.)@@ Веселов В.В. Эндоскопическое лечение больных с большими и гигантскими аденомами толстой кишки: диссертация… доктора медицинских наук: 14.00.14. Москва, 1997. 135 с.


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Khankin S.L., Rubtsov V.S., Napsheva A.M. Colorectal and Stomach Cancer, a New Look at the Features of Morphogenesis. Experimental and Clinical Gastroenterology. 2025;(3):13-28. https://doi.org/10.31146/1682-8658-ecg-235-3-13-28

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