Features of the microstructure and metabolism of the colon mucosa at the resection border in patients with colorectal cancer

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Abstract

BACKGROUND: In patients with colorectal cancer, the intestinal wall, which is not involved in the malignant process, despite histological signs of intactness, is characterized by impaired structure and metabolism. Modern optical bioimaging technologies make it possible to objectively assess these changes.

AIM: To study metabolism and morphological structure features of the mucous membrane of the relatively normal colon in patients with colorectal cancer.

MATERIAL AND METHODS: The object of study was the colon mucosa in patients with colorectal cancer stages I–IV. The study included 59 patients. There were 33 (56%) men, 26 (44%) women; median age — 67 [61; 74] years. In 10 cases, the tumor was localized in the right colon, in 9 — in the transverse colon, in 23 — in the sigmoid colon, in 17 — in the rectum. 7 samples were obtained from patients with stage I, 25 — with stage II, 21 — with stage III, 6 — with stage IV colorectal cancer. The metabolism of colon tissue from the mucosal side was studied using fluorescence-lifetime macroimaging, and the microstructure was studied using optical coherence tomography and histological examination. The results of calculating the weighted average fluorescence lifetime were presented as median values Me [Q1; Q3], comparison of this indicator between groups was carried out using the nonparametric Kruskal–Wallis test.

RESULTS: According to histological examination, progression signs of structural changes with increasing stage of colorectal cancer were revealed: from the conventional norm in samples with stage I to the appearance of signs of chronic colitis, atrophy and erosion of the mucous membrane in samples with stages II, III and IV. Visual analysis of optical coherence tomograms obtained from colon samples showed a high degree of agreement with histological data: the Spearman correlation coefficient was r=0.96. According to fluorescence-lifetime macroimaging, statistically significant differences (p=0.027) in the weighted average fluorescence lifetime were detected between stages IV and II of colorectal cancer: the values were 1.6 [1.4; 1.8] ns and 1.3 [1.1; 1.4] ns, respectively, which indicated an intensification of the glycolysis process in the tissues of the colon mucosa in stage IV colorectal cancer. Presumably, the identified changes will become the pathophysiological and anatomical basis of postoperative complications. In clinical oncology, it is advisable to use the obtained data to optimize the volume of intestinal resection and postoperative therapy algorithms.

CONCLUSION: Long-term tumor carriage and progression of colorectal cancer (invasion and metastasis) are associated with an increasing incidence of atrophy/erosion of the mucous membrane, the signs of which are determined both by optical coherence tomography and by histological examination.

About the authors

Maksim V. Bagryantsev

Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko

Author for correspondence.
Email: maks-bagryancev@mail.ru
ORCID iD: 0000-0003-2230-9431

M.D., Cand. Sci. (Med.), Сoloproctology Сenter

Russian Federation, Nizhny Novgorod

Aleksandr I. Abelevich

Privolzhsky Research Medical University

Email: aabelevich@yandex.ru
ORCID iD: 0000-0001-6015-4974

M.D., D. Sci. (Med.), Prof., Depart. of General, Operative Surgery and Topographic Anatomy

Russian Federation, Nizhny Novgorod

Ilya L. Dezorcev

Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko

Email: dezortsev-il@yandex.ru
ORCID iD: 0000-0003-3855-8686

M.D., Cand. Sci. (Med.), Head of Depart., Depart. of Coloproctology

Russian Federation, Nizhny Novgorod

Vladislav I. Shcheslavskiy

Privolzhsky Research Medical University

Email: vis@becker-hickl.de
ORCID iD: 0000-0003-3253-8211

Cand. Sci. (Phys.-Math.), Head of Lab., Laboratory. of Optical Spectroscopy and Microscopy

Russian Federation, Nizhny Novgorod

Elena B. Kiseleva

Privolzhsky Research Medical University

Email: kiseleva84@gmail.com
ORCID iD: 0000-0003-4769-417X

Cand. Sci. (Biol.), Senior Researcher, Laboratory of Optical Coherence Tomography, Research Institute of Experimental Oncology and Biomedical Technologies

Russian Federation, Nizhny Novgorod

References

  1. Clinical guidelines for the treatment of rectal cancer (2022). https://cr.minzdrav.gov.ru/schema/554_3 (access date: 02.10.2023). (In Russ.)
  2. Clinical guidelines for the treatment of colon cancer (2022). https://cr.minzdrav.gov.ru/schema/396_3 (access date: 02.10.2023). (In Russ.)
  3. Pallan A, Dedelaite M, Mirajkar N, Newman PA, Plowright J, Ashraf S. Postoperative complications of colorectal cancer. Clin Radiol. 2021;76(12):896–907. doi: 10.1016/j.crad.2021.06.002.
  4. Karachun AM, Samsonov DV. Bryushno-promezhnostnaya ekstirpaciya ili predel'no nizkaya rezekciya pryamoj kishki: vybor vracha ili pacienta? Journal of Emergency surgery named after II Dzhanelidze. 2022;(3):51–55. (In Russ.) doi: 10.54866/27129632_2022_3_50.
  5. Tsarkov PV, Efetov SK, Zubayraeva AA, Puzakov KV, Oganyan NV. Surgeon’s role in CT-based preoperative determination of inferior mesenteric artery anatomy in colorectal cancer treatment. Hirurgiya. Zhurnal im NI Pirogova. 2022;(9):40–49. (In Russ.) doi: 10.17116/hirurgia202209140.
  6. Verkuijl SJ, Furnée EJB, Kelder W, Hoff C, Hess DA, Wit F, Zijlstra RJ, Trzpis M, Broens PMA. Long-term bowel dysfunction and decline in quality of life following surgery for colon cancer: Call for personalized screening and treatment. Dis Colon Rectum. 2022;65(12):1531–1541. doi: 10.1097/DCR.0000000000002377.
  7. Van Rooijen S, Carli F, Dalton S, Thomas G, Bojesen R, Le Guen M, Barizien N, Awasthi R, Minnella E, Beijer S, Martínez-Palli G, van Lieshout R, Gögenur I, Feo C, Johansen C, Scheede-Bergdahl C, Roumen R, Schep G, Slooter G. Multimodal prehabilitation in colorectal cancer patients to improve functional capacity and reduce postoperative complications: The first international randomized controlled trial for multimodal prehabilitation. BMC Cancer. 2019;19(1):98. doi: 10.1186/s12885-018-5232-6.
  8. Lawrence VA, Hazuda HP, Cornell JE, Pederson T, Bradshaw PT, Mulrow CD, Page CP. Functional independence after major abdominal surgery in the elderly. J Am Coll Surg. 2004;199:762–772. doi: 10.1016/j.jamcollsurg.2004.05.280.
  9. Yde J, Larsen HM, Laurberg S, Krogh K, Moeller HB. Chronic diarrhoea following surgery for colon cancer-frequency, causes and treatment options. Int J Colorectal Dis. 2018;33(6):683–694. doi: 10.1007/s00384-018-2993-y.
  10. Hope C, Reilly J, Lund J, Andreyev H. Systematic review: the effect of right hemicolectomy for cancer on postoperative bowel function. Support Care Cancer. 2020;28(10):4549–4559. doi: 10.1007/s00520-020-05519-5.
  11. Bertelsen CA, Elfeki H, Neuenschwander AU, Laurberg S, Kristensen B, Emmertsen KJ. The risk of long-term bowel dysfunction after resection for sigmoid adenocarcinoma: A cross-sectional survey comparing complete mesocolic excision with conventional surgery. Colorectal Dis. 2018;20(9):O256–O266. doi: 10.1111/codi.14318.
  12. Larsen HM, Borre M, Christensen P, Mohr Drewes A, Laurberg S, Krogh K, Fassov J. Clinical evaluation and treatment of chronic bowel symptoms following cancer in the colon and pelvic organs. Acta Oncol. 2019;58(5):776–781. doi: 10.1080/0284186X.2018.1562211.
  13. Datta R, Gillette A, Stefely M, Skala MC. Recent innovations in fluorescence lifetime imaging microscopy for biology and medicine. J Biomed Opt. 2021;26(7):070603. doi: 10.1117/1.JBO.26.7.070603.
  14. Wang Y, Liu S, Lou S, Zhang W, Cai H, Chen X. Application of optical coherence tomography in clinical diagnosis. J Xray Sci Technol. 2019;27(6):995–1006. doi: 10.3233/XST-190559.
  15. Lukina M, Shimolina L, Kiselev N, Zagainov V, Komarov D, Zagaynova E, Shirmanova M. Interrogation of tumor metabolism in tissue samples ex vivo using fluorescence lifetime imaging of NAD(P)H. Methods Appl Fluoresc. 2019;8(1):014002. doi: 10.1088/2050-6120/ab4ed8.
  16. Shcheslavskiy VI, Shirmanova MV, Dudenkova VV, Lukyanov KA, Gavrina AI, Shumilova AV, Zagaynova E, Becker W. Fluorescence time-resolved macroimaging. Opt Lett. 2018;43(13):3152–3155. doi: 10.1364/OL.43.003152.
  17. Gelikonov VM, Romashov VN, Shabanov DV, Ksenofontov SYu, Terpelov DA, Shilyagin PA. Cross-polarization optical coherence tomography with active maintenance of the circular polarization of a sounding wave in a common path system. Radiophys Quant El. 2018;60:897–911. doi: 10.1007/s11141-018-9856-9.
  18. Yang Y, Li XJ, Li P, Guo XT. MicroRNA-145 regulates the proliferation, migration and invasion of human primary colon adenocarcinoma cells by targeting MAPK1. Int J Mol Med. 2018;42(6):3171–3180. doi: 10.3892/ijmm.2018.3904.
  19. Garrett WS. The gut microbiota and colon cancer. Science. 2019;364(6446):1133–1135. doi: 10.1126/science.aaw2367.
  20. Jiang C, Liu Y, Wen S, Xu C, Gu L. In silico development and clinical validation of novel 8 gene signature based on lipid metabolism related genes in colon adenocarcinoma. Pharmacol Res. 2021;169:105644. doi: 10.1016/j.phrs.2021.105644.
  21. Miao Y, Wang J, Ma X, Yang Y, Mi D. Identification prognosis-associated immune genes in colon adenocarcinoma. Biosci Rep. 2020;40(11):BSR20201734. doi: 10.1042/BSR20201734.
  22. Bagryancev MV, Ryabkov MG, Samojlenko VM, Bazaev AV, Dezorcev IL, Bunova SS, Batanov MA, Kiseleva EB. Epigenetic markers of colorectal cancer: clinical data analysis. Journal of experimental and clinical surgery. 2021;14(4):316–324. (In Russ.) doi: 10.18499/2070-478X-2021-14-4-316-324.
  23. Popovskaya TN, Zhukov VI, Perepadya SV. Disorders of protein and carbohydrate metabolism in patients with malignant intestinal tumors. Mіzhnarodnij medichnij zhurnal. 2018;24(1):60–63. (In Russ.)
  24. Briet F, Twomey C, Jeejeebhoy KN. Effect of malnutrition and short-term refeeding on peripheral blood mononuclear cell mitochondrial complex I activity in humans. Am J Clin Nutr. 2003;77(5):1304–1311. doi: 10.1093/ajcn/77.5.1304.
  25. Deng F, Zhou R, Lin C, Yang S, Wang H, Li W, Zheng K, Lin W, Li X, Yao X, Pan M, Zhao L. Tumor-secreted dickkopf2 accelerates aerobic glycolysis and promotes angiogenesis in colorectal cancer. Theranostics. 2019;9(4):1001–1014. doi: 10.7150/thno.30056.
  26. Yde J, Larsen HM, Laurberg S, Krogh K, Moeller HB. Chronic diarrhoea following surgery for colon cancer-frequency, causes and treatment options. Int J Colorectal Dis. 2018;33(6):683–694. doi: 10.1007/s00384-018-2993-y.
  27. Larsen HM, Borre M, Christensen P, Mohr Drewes A, Laurberg S, Krogh K, Fassov J. Clinical evaluation and treatment of chronic bowel symptoms following cancer in the colon and pelvic organs. Acta Oncol. 2019;58(5):776–781. doi: 10.1080/0284186X.2018.1562211.
  28. Izosimova AV, Shirmanova MV, Shcheslavskiy VI, Sachkova DA, Mozherov AM, Sharonov GV, Zagaynova EV, Yuzhakova DV. FLIM of NAD(P)H in lymphatic nodes resolves T-cell immune response to the tumor. Int J Mol Sci. 2022;23(24):15829. doi: 10.3390/ijms232415829.
  29. Kiseleva E, Ryabkov M, Baleev M, Bederina E, Shilyagin P, Moiseev A, Beschastnov V, Romanov I, Gelikonov G, Gladkova N. Prospects of intraoperative multimodal OCT application in patients with acute mesenteric ischemia. Diagnostics. 2021;11(4):705. doi: 10.3390/diagnostics11040705.
  30. Volz P, Schilrreff P, Brodwolf R, Wolff C, Stellmacher J, Balke J, Morilla MJ, Zoschke C, Schäfer-Korting M, Alexiev U. Pitfalls in using fluorescence tagging of nanomaterials: Tecto-dendrimers in skin tissue as investigated by Cluster-FLIM. Ann NY Acad Sci. 2017;1405(1):202–214. doi: 10.1111/nyas.13473.
  31. Jabbour JM, Cheng S, Malik BH, Cuenca R, Jo JA, Wright J, Cheng Y-SL, Maitland KC. Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer. J Biomed Opt. 2013;18(4):046012. doi: 10.1117/1.JBO.18.4.046012.
  32. Dravid UA, Mazumder N. Types of advanced optical microscopy techniques for breast cancer research: A review. Lasers Med Sci. 2018;33(9):1849–1858. doi: 10.1007/s10103-018-2659-6.
  33. Ouyang Y, Liu Y, Wang ZM, Liu Z, Wu M. FLIM as a promising tool for cancer diagnosis and treatment monitoring. Nanomicro Lett. 2021;13(1):133. doi: 10.1007/s40820-021-00653-z.
  34. Alfonso-Garcia A, Cevallos SA, Lee JY, Li C, Bec J, Bäumler AJ, Marcu L. Assessment of murine colon inflammation using intraluminal fluorescence lifetime imaging. Molecules. 2022;27(4):1317. doi: 10.3390/molecules27041317.
  35. Rück A, Hauser C, Mosch S, Kalinina S. Spectrally resolved fluorescence lifetime imaging to investigate cell metabolism in malignant and nonmalignant oral mucosa cells. J Biomed Opt. 2014;19(9):96005. doi: 10.1117/1.JBO.19.9.096005.
  36. Liu Z, Pouli D, Alonzo CA, Varone A, Karaliota S, Quinn KP, Münger K, Karalis KP, Georgakoudi I. Mapping metabolic changes by noninvasive, multiparametric, highresolution imaging using endogenous contrast. Sci Adv. 2018;4(3):eaap9302. doi: 10.1126/sciadv.aap9302.
  37. Nam HS, Kang WJ, Lee MW, Song JW, Kim JW, Oh WY, Yoo H. Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography. Biomed Opt Express. 2018;9(4):1930–1947. doi: 10.1364/BOE.9.001930.
  38. Shirmanova MV, Shcheslavskiy VI, Lukina MM, Becker W, Zagaynova EV. Exploring tumor metabolism with time-resolved fluorescence methods: from single cells to a whole tumor. In: Multimodal optical diagnostics of cancer. Tuchin V, Popp J, Zakharov V, editors. Cham: Springer; 2020. p. 133–155.

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2. Fig. 1. Histological picture of the colon mucosa at the resection border in CRC stages I (a1, б1), II (a2, б2, в1), III (a3, б3, в2) and IV (a4, б4, в3). As the stage increases, there is an increase in signs of tissue damage to the mucous and submucosal membranes

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3. Fig. 2. OCT images obtained during contact examination of colon samples from patients from the mucosal side in the study groups. Typical cross-sectional OCT images of colon samples taken at the resection border are presented, with a histologically confirmed norm (without inflammation) (a), with an inflammatory process in the mucous and submucous membranes of the intestinal wall (б, в) and erosion (г) for colorectal cancer stages I (a), II (б), III (в) and IV (г), respectively. White arrows indicate lymphatic vessels in the submucosal layer, yellow dotted arrows indicate the area of interstitial edema at the border of the submucosal and muscular layers. The blue bracket indicates the mucous membrane, and the red bracket indicates the submucosa. OCT — optical coherence tomography

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4. Fig. 3. Results of the study of mucosal tissues of colon samples from patients with various stages of colorectal cancer, taken at the resection margins, using the macroFLIM method; a, б, в, г — macro-FLIM images, weighted average lifetime of NADPH fluorescence (τm) in the study groups; д — diagram of quantitative analysis of the parameter τm in the study groups. FLIM — fluorescence-lifetime imaging microscopy. NADPH — nicotinamide adenine dinucleotide phosphate (reduced form)

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