Проблемы и перспективы применения морфологических факторов риска метастазирования в лимфатические узлы при колоректальном раке Т1 (обзор литературы)
https://doi.org/10.33878/2073-7556-2025-24-4-177-187
Аннотация
Диагностика и лечение раннего КРР с подслизистой инвазией (Т1 КРР) является актуальной и сложной проблемой современной онкологии. Расширение возможностей эндоскопических технологий позволяет проводить органосохраняющее лечение с локальным удалением опухоли с подслизистой инвазией. Основной проблемой в органосохраняющем лечении Т1 КРР является отбор пациентов и максимально точная оценка риска метастазирования опухоли в каждом конкретном случае. В настоящее время морфологические характеристики опухоли являются основными предикторами метастазирования при Т1 КРР. Однако применение рекомендованных морфологических предикторов обозначило определенные проблемы в отборе пациентов с завышением показаний к дополнительному хирургическому лечению.
Ключевые слова
колоректальный рак Т1,
морфологические факторы риска метастазирования в лимфоузлы,
оценка риска метастазирования при Т1 КРР
При поддержке: работа выполнена без спонсорской поддержки
Об авторе
О. А. Майновская
ФГБУ «НМИЦ колопроктологии имени А.Н. Рыжих» Минздрава России
Россия
Россия
Майновская Ольга Александровна
ул. Саляма Адиля, д. 2, г. Москва, 123423
Список литературы
1. Каприн А.Д., Старинский В.В., Шахзадова О.А. Состояние онкологической помощи населению России в 2020 году. М.: МНИОИ им. П.А. Герцена филиал ФГБУ «НМИРЦ» Минздрава России; 2021. doi: 10.1017/CBO9781107415324.004
2. ВОЗ. Колоретальный рак. 2023.
3. Taylor EF, Morris EJA, Thomas JD, et al. Major improvement in the stage profile of tumours diagnosed in the NHS bowel cancer screening programme. Gut. 2010;59(A31).
4. Logan RFA, Patnick J, Nickerson C, et al. English Bowel Cancer Screening Evaluation Committee. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut. 2012; (61):1439–1446.
5. Toes-Zoutendijk E, Kooyker A.I, Elferink M.A, et al. LECO working group. Stage distribution of screen-detected colorectal cancers in the Netherlands. Gut. 2018 Sep;67(9):1745–1746. doi: 10.1136/gutjnl-2017-315111.
6. Ueno H, Mochizuki H, Hashiguchi Y, et al. Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology. 2004;(127):385–94. doi: 10.1053/j.gastro.2004.04.022.
7. Bosch SL, Teerenstra S, de Wilt JHW, et al. Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions. Endoscopy. 2013; (45): 827–834.doi: 10.1055/s-0033-1344238
8. Zaffalon D, Daca-Alvarez M, Saez de Gordoa K, et al. Dilemmas in the Clinical Management of pT1 Colorectal Cancer. Cancers. 2023; (15):3511. https://doi.org/10.3390/cancers15133511.
9. Labianca R, Nordlinger B, Beretta GD, et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2013; (24 Suppl 6):64-72. doi:10.1093/annonc/mdt354.
10. Argilés G, Tabernero J, Labianca R, et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31 (10):1291-1305 ttps://doi.org/10.1016/j.annonc.2020.06.022
11. Pimentel-Nunes P, Libanio D, Bastiaansen BAJ, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2022; (54): 591–622. doi. org/10. 1055/a- 1811–7025.
12. Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020; 25 (1):1-42. doi: 10.1007/s10147-019-01485-z
13. Japanese Society for Cancer of the Colon and Rectum Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma: the 3rd English Edition [Secondary Publication]. J Anus Rectum Colon. 2019; 3:175–195. doi. org/ 10. 23922/ jarc.2019- 018.
14. Benson A, Alan P. Venook A, et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(3):329–359 doi: 10.6004/jnccn.2021.0012
15. Benson A, Venook AP, Al-Hawary MM, et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Oct;20(10):1139-1167. doi: 10.6004/jnccn.2022.0051
16. Yoshii S, Nojima M, Nosho K, et al. Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors. Clin Gastroenterol Hepatol. 2014; 12: 292–302.e3. doi: 10.1016/j.cgh.2013.08.008.
17. Ozeki T, Shimura T, Ozeki T, et al. The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery. Cancers. 2022;14(3): 822. doi.org/10.3390/cancers14030822.
18. Ichimasa K, Kudo SE, Miyachi H, et al. Current problems and perspectives of pathological risk factors for lymph node metastasis in T1 colorectal cancer: Systematic review. Dig Endosc. 2022; 34:901–12. doi: 10.1111/den.14220
19. Zaffalon D, Daca-Alvarez M, Saez de Gordoa K, et al. Dilemmas in the Clinical Management of pT1 Colorectal Cancer. Cancers. 2023; 15:3511.https://doi.org/10.3390/cancers15133511
20. Choi YS, Kim WS, Hwang SW, et al. Clinical outcomes of submucosal colorectal cancer diagnosed after endoscopic resection: a focus on the need for surgery. Intest Res. 2020;18:96–106.
21. Beaton C, Twine CP, Williams GL, et al.Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Colorectal Dis. 2013 Jul;15(7):788-97. doi: 10.1111/codi.12129.
22. Ebbehøj A, Jørgensen L, Krarup P, et al. Histopathological risk factors for lymph node metastases in T1 colorectal cancer: meta-analysis. BJS. 2021; 108(7): 769–776. doi: 10.1093/bjs/znab168.
23. Zwager LW, Bastiaansen BAJ, Montazeri NSM, et al. Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: A meta-analysis. Gastroenterology. 2022; 163:174–89. doi: 10.1053/j.gastro.2022.04.010
24. Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2020; Nov;115(11):1751-1767. doi: 10.14309/ajg.0000000000001013.
25. Nakadoi K, Tanaka S, Kanao H, et al. Management of T1 colorectal carcinoma with special reference to criteria for curative endoscopic resection. J Gastroenterol Hepatol. 2012; 27: 1057-1062. doi: 10.1111/j.1440-1746.2011.07041.x.
26. Backes Y, Elias S, Groen J, et al. Histologic factors associated with need for surgery in patients with pedunculated T1 colorectal carcinomas. Gastroenterology. 2018; 154:1647–59. doi: 10.1053/j.gastro.2018.01.023.
27. Aizawa D,•Sugino T, Oishi T, et al. The essential problem of over-measuring the depth of submucosal invasion in pT1 colorectal cancer. Virchows Archiv. 2021; Nov;05: doi.org/10.1007/s00428-021-03221-3
28. Kitajima K, Fujimori T, Fujii S, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol 2004;39: 534-543 doi: 10.1007/s00535-004-1339-4.
29. Haggitt R, Glotzbach R, Soffer E, et al. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology. 1985; 89(2): 328-36. doi: 10.1016/0016-5085(85)90333-6.
30. Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy. 1993; 25: 455–461. doi: 10.1055/s-2007-1010367.
31. Kikuchi R, Takano M, Takagi K, et al. Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines. Dis Colon Rectum. 1995; 38 (12):1286–1295. doi: 10.1007/BF02049154.
32. Kouyama Y, Kudo S, Miyachi H, et al. Practical problems of measuring depth of su:bmucosal invasion in T1 colorectal carcinomas. Int J Colorectal Dis. 2016; 31:137–46. doi: 10.1007/s00384-015-2403-7
33. Ito T, Eishi Y, Kobayashi D, et al. A risk stratification for nodalmetastasis in T1 colorectal cancer after successful therapeutic endoscopy. Gastrointest Endosc. 2022; Jul;96(1):131-134. doi: 10.1016/j.gie.2022.02.041.
34. Davenport A, Morris J, Pritchard SA, et al. Interobserver variability amongst gastrointestinal pathologists in assessing prognostic parameters of malignant colorectal polyps: A cause for concern. Tech Coloproctology. 2016; 20:647–652. doi: 10.1007/s10151-016-1513-8.
35. Suzuki T, Sadahiro S, Mukoyama S, et al. Risk of lymph node and distant metastases in patients with early invasive colorectal cancer classified as Haggitt’s level 4 invasion: image analysis of submucosal layer invasion. Dis Colon Rectum. 2003; 46(2):203–208. doi: 10.1007/s10350-004-6525-1.
36. Cracco N, Todaro V, Pedrazzi G, et al. The risk of lymph node metastasis in T1 colorectal ancer: new parameters to assess the degree of submucosal invasion. Int J Colorectal Dis. 2021; 36:41–5. doi: 10.1007/s00384-020-03738-0.
37. Yim K, Won D, Lee I, et al. Novel predictors for lymph node metastasis in submucosal invasive colorectal carcinoma. World J Gastroenterol. 2017; 23(32):5936-5944. doi: doi.org/10.3748/wjg.v23.i32.5936.
38. Barel F, Cariou M, Philippe S, et al. Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer. Sci Rep. 2019. 9(1):8342 1–12.doi.org/10.1038/s41598-019-44894-w
39. TohE, Broen P, Morris E, Botterill I, et al. Area of submucosal invasion and width of invasion predicts lymph node metastasis in pT1 colorectal cancers. Dis Colon Rectum. 2015;58(4):393–340 doi: 10.1097/DCR.0000000000000315
40. Egashira Y, Yoshida T, Hirata I, et al. Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol. 2004; 17(5):503–511 doi: 10.1038/modpathol.3800030
41. Wang LM, Guy R, Fryer E, et al. The Ueno method for substaging pT1 colorectal adenocarcinoma by depth and width measurement: an interobserver study. Color Dis. 2015; 17(8):674–681. doi: 10.1111/codi.12910.
42. Maynovskaya O, Rybakov E, Chernyshov S, et al. Are the width, length, depth, and area of submucosal invasion predictive of lymph node metastasis in pT1 colorectal cancer? Ann Coloproctol. 2023; 39(6):484-492.
43. Wada H, Shiozawa M, Katayama K, et al. Systematic review and meta-analysis of histopathological predictive factors for lymph node metastasis in T1 colorectal cancer. J Gastroenterol. 2015; 50: 727-734. doi: 10.1007/s00535-015-1057-0.
44. Brockmoeller SF, West NP. Predicting systemic spread in early colorectal cancer: Can we do better? World J Gastroenterol. (2019) 25:2887–97. doi: 10.3748/wjg.v25.i23.2887
45. Oka S, Tanaka S, Kajiwara Y, et al. Treatment decision for locally resected T1 colorectal carcinoma-verification of the Japanese guideline criteria for additional surgery based on long-term clinical outcomes. Am J Gastroenterol. (2024) 119:2019–27. doi: 10.14309/ajg.0000000000002715
46. Haasnoot KJC, Backes Y, Moons LMG, et al. Associations of non-pedunculated T1 colorectal adenocarcinoma outcome with consensus molecular subtypes, immunoscore, and microsatellite status: A multicenter case-cohort study. Mod Pathol. 2020; 33: 2626–2636.doi.org/10.1038/s41379-020-0598-9.
47. Komuta K, Batts K, Jessurun J, et al. Interobserver variability in the pathological assessment of malignant colorectal polyps. Br J Surg. 2004; 91(11): 1479–84. doi: 10.1002/bjs.4588.
48. Ueno H, Hase K, Hashiguchi Y, et al. Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review. J Gastroenterol. 2014; 49: 1314-1323 doi: 10.1007/s00535-013-0881-3.
49. Yoshida N, Nakanishi M, Inoue K, et al. Pure welldifferentiated adenocarcinoma is a safe factor for lymph node metastasis in T1 and T2 colorectal cancer: A pilot study. Gastroenterol Res Pract. 2018; 2018: 8798405 doi: 10.1155/2018/8798405.
50. WHO Classification of Tumors Editorial Board. Digestive system Tumours. 5th.ed. Lyon (France): International agency for Research on Cancer; 2019. https:// www. iarc. fr/ fr/ news- events/ publi cation- of- whoclassification- of- tumours- 5th- editi on- volume- 1- digestive- systemtumours/
51. Quirke P, Risio M, Lambert R, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition Quality assurance in pathology in colorectal cancer screening and diagnosis. Endoscopy. 2012; 44: SE116–SE130. doi.org/10.1055/s-0032-1309797.
52. Carey F, Newbold M, Quirke P, et al. Reporting lesions in the NHS Bowel Cancer Screening Programme: Guidelines from the Bowel Cancer Screening Programme Pathology Group 2007;1–24. NHS BCSP publication. Available at: http://www.cancerscreening.nhs.uk/bowel/publications/nhsbcsp01.pdf
53. Ueno H, Murphy J, Jass JR, et al. Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology. 2002;40:127–132. doi: 10.1046/j.1365-2559.2002.01324.x.
54. Ueno H, Kajiwara Y, Shimazaki H, et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol. 2012; 36: 193-201 doi: 10.1097/PAS.0b013e318235edee.
55. Akishima-Fukasawa Y, Ishikawa Y, Akasaka Y, et al. Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer. Histopathology. 2011;59: 470–481. doi: 10.1111/j.1365-2559.2011.03964.x.
56. Rogers AC, Winter DC, Heeney A, et al. Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer. 2016; Sep 27;115(7):831-40. doi: 10.1038/bjc.2016.274
57. Cappellesso R, Luchini C, Veronese N, et al. Tumor budding as a risk factor for nodal metastasis in pT1 colorectal cancers: a meta-analysis. Hum Pathol. 2017; 65: 62-70 doi: 10.1016/j.humpath.2017.04.013.
58. Puppa G, Senore C, Sheahan K, et al. Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy. Histopathology. 2012; 61:562–575.
59. LugliA, Kirsch R, Ajioka Y, et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol. 2017;30:1299–311. doi: 10.1038/modpathol.2017.46.
60. Barresi V, Branca G, Ieni A, et al. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer. Virchows Arch. 2014; 464: 655-662. doi: 10.1007/s00428-014-1580-z.
61. Reggiani Bonetti L, Barresi V, Bettelli S, et al. Poorly differentiated clusters (PDC) in colorectal cancer: what is and ought to be known. Diagn Pathol. 2016; 11:31. doi: 10.1186/s13000-016-0481-7.
62. Konishi T, Shimada Y, Lee LH, et al. Poorly Differentiated Clusters Predict Colon Cancer Recurrence: An In-Depth Comparative Analysis of Invasive-Front Prognostic Markers. Am J Surg Pathol. 2018; June; 42(6): 705–714.doi: 10.1097/PAS.0000000000001059.
63. Shivji S, Conner JR, Barresi V, et al. Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice. Histopathology. 2020;77(3):351-368. doi: 10.1111/his.14128.
64. Dykstra MA, Gimon TI, Ronksley PE, et al. Classic and novel histopathologic risk factors for lymph node metastasis in T1 colorectal cancer: A systematic review and meta-analysis. Dis Colon Rectum. 2021; 64:1139–50. doi: 10.1097/DCR.0000000000002164.
65. Washington M, Berlin J, Branton F, et al. Protocol for the examination of specimens from patients with primary carcinomas of the colon and rectum. Arch Pathol Lab Med. 2009 Oct;133(10):1539-51. doi: 10.5858/133.10.
66. Harris EI, Lewin DN, Wang HL, et al. Lymphovascular invasion in colorectal cancer: an interobserver variability study. Am J Surg Pathol. 2008; 32:1816e21. doi.org/10.1097/PAS.0b013e3181816083.
67. Smith KJ, Jones PF, Burke DA, et al. Lymphatic vessel distribution in the mucosa and submucosa and potential implications for T1 colorectal tumors. Diseases of the Colon and Rectum. 01 Jan 2011, 54(1):35-40. doi.org/10.1007/dcr.0b013e3181fb0e7a.
68. Betge J, Pollheimer MJ, Lindtner RA, et al. Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer. 2012; 118: 628-638. doi: 10.1002/cncr.26310.
69. Rönnow CF, Arthursson V, Toth E, et al. Lymphovascular infiltration, not depth of invasion, is the critical risk factor of metastases in early colorectal cancer: retrospective population-based cohort study on prospectively collected data, including validation. Ann Surg. Epub 2020; Mar 13. doi.org/10.1097/SLA.0000000000003854.
70. Bianchi G, Annicchiarico A, Morini A, et al. Three distinct outcomes in patients with colorectal adenocarcinoma and lymphovascular invasion: the good, the bad, and the ugly. Int J Colorectal Dis. 2021 Dec;36(12):2671-2681. doi: 10.1007/s00384-021-04004-7.
71. Cserni G, Sejben I, Bori R. Diagnosing vascular invasion in colorectal carcinomas: improving reproducibility and potential pitfalls. J Clin Pathol. 2013;66:543–7. doi: 10.1136/jclinpath-2013-201587.
72. Kojima M, Shimazaki H, Iwaya K, et al. Pathologicaldiagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer: aframework for developing an objective pathological diagnostic system using the Delphi method, from the Pathology Working Group of the Japanese Society for Cancer of the Colon and Rectum. J Clin Pathol. (2013) 66:551–8. doi: 10.1136/jclinpath-2012-201076
73. Ishii M, Ota M, Saito S, et al. Lymphatic vessel invasion detected by monoclonal antibody D2-40 as a predictor of lymph node metastasis in T1 colorectal cancer. Int J Colorectal Dis. 2009; 24: 1069-1074. doi: 10.1007/s00384-009-0699-x.
74. Watanabe J, Katsuro Ichimasa K, Kataoka Y, et al. Additional staining for lymphovascular invasion is associated with increased estimation of lymph node metastasis in patients with T1 colorectal cancer: Systematic review and meta-analysis. Digestive Endoscopy. 2024; 36: 533–545. doi: 10.1111/den.14691.
75. Smits LJH., Vink-Börger E, Lijnschoten G, et al. Diagnostic variability in the histopathological assessment of advanced colorectal adenomas and early colorectal cancer in a screening population. Histopathology. 2022; 80: 790–798doi.org/10.1111/his.14601
76. Dykstra MA, Gimon TI, Ronksley PE, et al. Classic and novel histopathologic risk factors for lymph node metastasis in T1 colorectal cancer: A systematic review and meta-analysis. Dis Colon Rectum. (2021) 64:1139–50. doi: 10.1097/DCR.0000000000002164баддингкластеры
77. Miyachi H, Kudo S, Ichimasa K, et al. Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis. Journal of Gastroenterology and Hepatology. 2016; 31 (6): 1126–1132. doi: 10.1111/jgh.13257.
78. Gijsbers K, de Graaf W, Moons LMG, et al. High practice variation in risk stratification, baseline oncological staging, and follow-up strategies for T1 colorectal cancers in the Netherlands. (on behalf of the Dutch T1 CRC Working Group). Endosc Int Open. 2020 Sep;8(9):E1117-E1122. doi: 10.1055/a-1192-3545.
79. Kouyama Y, Kudo S, Ichimasa K, et al. Endoscopic resection alone as a potential treatment method for low-risk deep invasive T1 colorectal cancer. iGIE. 2023;2 (4):503-509. doi.org/10.1016/j.igie.2023.09.007.
80. Tanino F, Yamashita K, Morimoto S, et al. Comparative prediction of lymph node metastasis in pT1 colorectal cancer among Western and Japanese guidelines. Front Oncol. 2024;14:1475270. doi: 10.3389/fonc.2024.1475270.
81. Pontarollo G,•Bonjourm M, Walter T. Histopronostic factors in superficial colorectal adenocarcinomas treated by endoscopy: reproducibility and impact of immunohistochemistry and digital pathology. Virchows Archiv. 2024;485:233–244. doi.org/10.1007/s00428-023-03722-3
82. Kajiwara Y, Oka S, Tanaka S, et al. Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study. Gastrointest Endosc. 2023;97:1119–1128.e5. doi: 10.1016/j.gie.2023.01.022.
83. Yan S, Ding H, Zhao X, et al.Development and validation of a nomogram for further decision of radical surgery in pT1 colorectal cancer after local resection. Int J Colorectal Dis. 2021; 36:1499–506. doi: 10.1007/s00384-021-03928-4.
84. Ichimasa K, Kudo SE, Mori Y, et al. Artificial intelligence may help in predicting the need for additional surgery after endoscopic resection of T1 colorectal cancer. Endoscopy. 2018; 50:230–40. doi: 10.1055/s-0043-122385.
85. Kudo SE, Ichimasa K, Villard B, et al. Artificial intelligence system to determine risk of T1 colorectal cancer metastasis to lymph node. Gastroenterology. 2021;160:1075–1084.e2. doi: 10.1053/j.gastro.2020.09.027.
Рецензия
Для цитирования:
Майновская О.А. Проблемы и перспективы применения морфологических факторов риска метастазирования в лимфатические узлы при колоректальном раке Т1 (обзор литературы). Колопроктология. 2025;24(4):177-187. https://doi.org/10.33878/2073-7556-2025-24-4-177-187
For citation:
Mainovskaya O.A. Problems and prospects of using morphological risk factors for lymph node metastasis in T1 colorectal cancer (review). Koloproktologia. 2025;24(4):177-187. (In Russ.) https://doi.org/10.33878/2073-7556-2025-24-4-177-187
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