{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:26:54Z","timestamp":1760059614256,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PI20\/00863","2017 SGR 1035","202208320022"],"award-info":[{"award-number":["PI20\/00863","2017 SGR 1035","202208320022"]}]},{"name":"European Regional Development Fund (ERDF)","award":["PI20\/00863","2017 SGR 1035","202208320022"],"award-info":[{"award-number":["PI20\/00863","2017 SGR 1035","202208320022"]}]},{"name":"CIBEREHD program from Instituto de Salud Carlos III","award":["PI20\/00863","2017 SGR 1035","202208320022"],"award-info":[{"award-number":["PI20\/00863","2017 SGR 1035","202208320022"]}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["PI20\/00863","2017 SGR 1035","202208320022"],"award-info":[{"award-number":["PI20\/00863","2017 SGR 1035","202208320022"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["PI20\/00863","2017 SGR 1035","202208320022"],"award-info":[{"award-number":["PI20\/00863","2017 SGR 1035","202208320022"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Lymph node metastases (LNM) undetected by standard hematoxylin and eosin (H&amp;E) have been associated with unfavorable prognosis in colorectal cancer. The One-Step Nucleic Acid Amplification (OSNA) assay has demonstrated superior sensitivity in detecting LNM compared to H&amp;E. We aimed to assess the performance of OSNA in detecting LNM, as well as its prognostic value in rectal cancer (RC) patients. Methods: Lymph nodes (LNs) of patients from 15 centers were analyzed by both H&amp;E and OSNA. The total tumor load (TTL) was defined as the sum of cytokeratin 19 mRNA copies\/\u00b5L in all LNs from a surgical specimen, using a threshold of 250 copies\/\u03bcL for OSNA positivity. Cox proportional hazard regression was used to assess the effect of TTL \u2265 250 or 6000 copies\/\u03bcL on cancer-specific survival (CSS) and recurrence-free survival (RFS), with Firth\u2019s method applied to account for low event rate. Results: A total of 97 RC patients were included. Of these, 84 patients were eligible for survival analysis. The sensitivity and specificity of OSNA, compared to H&amp;E, were 91.7% and 84.7%, respectively. TTL \u2265 6000 versus &lt;6000 copies\/\u03bcL was related to worse CSS and RFS. When dividing TTL into three groups: \u2264250, 250\u20136000, and &gt;6000 copies\/\u03bcL, only TTL \u2265 6000 copies\/\u03bcL was significantly associated with worse CSS and RFS. Conclusions: The OSNA assay is highly sensitive for detecting LNM in RC patients. A TTL of \u22656000 copies\/\u03bcL could identify a subset of RC patients with worse CSS and RFS who might benefit from adjuvant treatment or intensive surveillance.<\/jats:p>","DOI":"10.3390\/cancers17132141","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T03:39:59Z","timestamp":1750909199000},"page":"2141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance and Prognostic Relevance of Lymph Node Assessment by One-Step Nucleic Acid Amplification Assay in Rectal Cancer: A Multicenter Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1784-6400","authenticated-orcid":false,"given":"Qing","family":"Liu","sequence":"first","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-2959","authenticated-orcid":false,"given":"Sandra","family":"Lopez-Prades","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8106-6121","authenticated-orcid":false,"given":"Karmele","family":"Saez de Gordoa","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-3425","authenticated-orcid":false,"given":"Maite","family":"Rodrigo-Calvo","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3445-9744","authenticated-orcid":false,"given":"Mireia","family":"Garcia","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Ruiz Martin","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitario de Toledo, 45004 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-8484","authenticated-orcid":false,"given":"Angel","family":"Romo","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitario de Toledo, 45004 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-8302","authenticated-orcid":false,"given":"Ignacio","family":"Pinilla","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitario Severo Ochoa, 28911 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-4087","authenticated-orcid":false,"given":"Jordi","family":"Tarragona","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2876-6732","authenticated-orcid":false,"given":"Bego\u00f1a Otero","family":"Alen","sequence":"additional","affiliation":[{"name":"Pathology Department, University Hospital Complex A Coru\u00f1a (CHUAC), 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Camps","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"},{"name":"Cell Biology and Medical Genetics Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Autonomous University of Barcelona (UAB), 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2142-0608","authenticated-orcid":false,"given":"Ivan","family":"Archilla","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3063-0110","authenticated-orcid":false,"given":"Miriam","family":"Cuatrecasas","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Pathology Department, Hospital Clinic Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1053\/j.gastro.2019.07.055","article-title":"Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults","volume":"158","author":"Stoffel","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_3","first-page":"89","article-title":"Epidemiology of Colorectal Cancer: Incidence, Mortality, Survival, and Risk Factors","volume":"14","author":"Rawla","year":"2019","journal-title":"Prz. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s13304-020-00703-y","article-title":"Colorectal Cancer-Screening Program Improves Both Short- and Long-Term Outcomes: A Single-Center Experience in Trieste","volume":"72","author":"Losurdo","year":"2020","journal-title":"Updates Surg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jiang, H., Zhang, P., Gu, K., Gong, Y., Peng, P., Shi, Y., Ai, D., Chen, W., and Fu, C. (2022). Cost-Effectiveness Analysis of a Community-Based Colorectal Cancer Screening Program in Shanghai, China. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.986728"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.amjsurg.2022.03.034","article-title":"An Updated Review of the Methods, Guidelines of, and Controversies on Screening for Colorectal Cancer","volume":"224","author":"Emile","year":"2022","journal-title":"Am. J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.3748\/wjg.v27.i39.6689","article-title":"Impact of a Colorectal Cancer Screening Program Implantation on Delays and Prognosis of Non-Screening Detected Colorectal Cancer","volume":"27","author":"Cubiella","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3393\/ac.2019.06.12","article-title":"Clinical Implications of Lymph Node Metastasis in Colorectal Cancer: Current Status and Future Perspectives","volume":"35","author":"Kim","year":"2019","journal-title":"Ann. Coloproctol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1245\/s10434-006-9120-y","article-title":"The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-Analysis","volume":"13","author":"Iddings","year":"2006","journal-title":"Ann. Surg. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejso.2013.12.002","article-title":"The Prognostic Value of Micrometastases and Isolated Tumour Cells in Histologically Negative Lymph Nodes of Patients with Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"40","author":"Sloothaak","year":"2014","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1200\/JCO.2011.36.9504","article-title":"Molecular Detection of Tumor Cells in Regional Lymph Nodes Is Associated with Disease Recurrence and Poor Survival in Node-Negative Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"30","author":"Rahbari","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s00384-012-1636-y","article-title":"Prognostic Significance of Histologically Detected Lymph Node Micrometastases of Sizes between 0.2 and 2 mm in Colorectal Cancer","volume":"28","author":"Herbst","year":"2013","journal-title":"Int. J. Color. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1007\/BF02236701","article-title":"Limitations with Light Microscopy in the Detection of Colorectal Cancer Cells","volume":"42","author":"Hitchcock","year":"1999","journal-title":"Dis. Colon Rectum"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1111\/ans.16758","article-title":"Survival in Stage IIB\/C Compared to Stage IIIA Rectal Cancer: An Australian Experience Affirming That Size Does Matter","volume":"91","author":"Mourad","year":"2021","journal-title":"ANZ J. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.7150\/jca.23311","article-title":"Survival Contradiction Between Stage IIA and Stage IIIA Rectal Cancer: A Retrospective Study","volume":"9","author":"Mo","year":"2018","journal-title":"J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Vedire, Y.R., Mukherjee, S., Dondapati, S., and Yendamuri, S. (2023). Association Between Visceral Obesity, Metformin Use, and Recurrence Risk in Early-Stage Colorectal Cancer. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-34690-y"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nakagami, Y., Hazama, S., Suzuki, N., Yoshida, S., Tomochika, S., Matsui, H., Shindo, Y., Tokumitsu, Y., Matsukuma, S., and Watanabe, Y. (2022). CD4 and FOXP3 as Predictive Markers for the Recurrence of T3\/T4a Stage II Colorectal Cancer: Applying a Novel Discrete Bayes Decision Rule. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10181-7"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/ags3.12576","article-title":"Micrometastasis in Lymph Nodes of Colorectal Cancer","volume":"6","author":"Yamamoto","year":"2022","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.annonc.2020.06.022","article-title":"Localised Colon Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"31","author":"Tabernero","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_20","first-page":"759","article-title":"Immunohistochemical Assessment of Localization and Frequency of Micrometastases in Lymph Nodes of Colorectal Cancer","volume":"8","author":"Noura","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1533033819832856","DOI":"10.1177\/1533033819832856","article-title":"Aberrant Cytokeratin 20 mRNA Expression in Peripheral Blood and Lymph Nodes Indicates Micrometastasis and Poor Prognosis in Patients with Gastric Carcinoma","volume":"18","author":"You","year":"2019","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/1097-0215(20010920)95:5<307::AID-IJC0153>3.0.CO;2-Q","article-title":"Reverse Transcription-Polymerase Chain Reaction Assay for Multiple mRNA Markers in the Detection of Breast Cancer Metastases in Sentinel Lymph Nodes","volume":"95","author":"Manzotti","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1245\/s10434-010-1539-5","article-title":"OSNA-Based Novel Molecular Testing for Lymph Node Metastases in Colorectal Cancer Patients: Results from a Multicenter Clinical Performance Study in Japan","volume":"18","author":"Yamamoto","year":"2011","journal-title":"Ann. Surg. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1245\/s10434-015-4880-x","article-title":"OSNA-Assisted Molecular Staging in Colorectal Cancer: A Prospective Multicenter Trial in Japan","volume":"23","author":"Yamamoto","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s40258-019-00482-7","article-title":"Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma","volume":"17","author":"Archilla","year":"2019","journal-title":"Appl. Health Econ. Health Policy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00303","DOI":"10.14309\/ctg.0000000000000303","article-title":"Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma?","volume":"12","author":"Archilla","year":"2021","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1245\/s10434-019-07971-y","article-title":"Lymph Node Positivity in One-Step Nucleic Acid Amplification Is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study","volume":"27","author":"Itabashi","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Paschke, S., Jafarov, S., Staib, L., Kreuser, E.-D., Maulbecker-Armstrong, C., Roitman, M., Holm, T., Harris, C.C., Link, K.-H., and Kornmann, M. (2018). Are Colon and Rectal Cancer Two Different Tumor Entities? A Proposal to Abandon the Term Colorectal Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092577"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/s11596-021-2356-8","article-title":"Distinguishing Rectal Cancer from Colon Cancer Based on the Support Vector Machine Method and RNA-Sequencing Data","volume":"41","author":"Zhang","year":"2021","journal-title":"Curr. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wu, X., Yang, Q., Leng, L., Yang, P., and Zhu, Z. (2025). Altered Metabolic Profiles in Colon and Rectal Cancer. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-96004-8"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Markowski, A.R., B\u0142achnio-Zabielska, A.U., Pogodzi\u0144ska, K., Markowska, A.J., and Zabielski, P. (2023). Diverse Sphingolipid Profiles in Rectal and Colon Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310867"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ctrv.2015.06.007","article-title":"Rectal and Colon Cancer: Not Just a Different Anatomic Site","volume":"41","author":"Tamas","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_33","first-page":"54","article-title":"Long-Term Results of 2 Adjuvant Trials Reveal Differences in Chemosensitivity and the Pattern of Metastases Between Colon Cancer and Rectal Cancer","volume":"12","author":"Kornmann","year":"2013","journal-title":"Clin. Color. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00268-001-0182-5","article-title":"Surgery of Colorectal Cancer: Surgical Morbidity and Five- and Ten-Year Results in 2400 Patients\u2014Monoinstitutional Experience","volume":"26","author":"Staib","year":"2002","journal-title":"World J. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1136\/gutjnl-2020-320625","article-title":"Colon and Rectal Cancer Survival in Seven High-Income Countries 2010\u20132014: Variation by Age and Stage at Diagnosis (the ICBP SURVMARK-2 Project)","volume":"70","author":"Araghi","year":"2021","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, Y.-C., Lee, Y.-L., Chuang, J.-P., and Lee, J.-C. (2013). Differences in Survival between Colon and Rectal Cancer from SEER Data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078709"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E114","DOI":"10.1111\/ans.13730","article-title":"Improved Survival for Rectal Cancer Compared to Colon Cancer: The Four Cohort Study","volume":"88","author":"Buchwald","year":"2018","journal-title":"ANZ J. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00384-015-2219-5","article-title":"Outcome for Stage II and III Rectal and Colon Cancer Equally Good after Treatment Improvement over Three Decades","volume":"30","author":"Fischer","year":"2015","journal-title":"Int. J. Color. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., G\u00f8tzsche, P.C., Vandenbroucke, J.P., and STROBE Initiative (2007). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040296"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12967-016-1114-3","article-title":"Lymph Node Pooling: A Feasible and Efficient Method of Lymph Node Molecular Staging in Colorectal Carcinoma","volume":"15","author":"Rakislova","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Saez De Gordoa, K., Rodrigo-Calvo, M.T., Archilla, I., Lopez-Prades, S., Diaz, A., Tarragona, J., Machado, I., Ruiz Mart\u00edn, J., Zaffalon, D., and Daca-Alvarez, M. (2023). Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study. Cancers, 15.","DOI":"10.3390\/cancers15225481"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00428-016-1990-1","article-title":"Molecularly Determined Total Tumour Load in Lymph Nodes of Stage I\u2013II Colon Cancer Patients Correlates with High-Risk Factors. A Multicentre Prospective Study","volume":"469","author":"Aldecoa","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.ejso.2020.12.001","article-title":"The Evolving Role of One-Step Nucleic Acid Amplification (OSNA) for the Intra-Operative Detection of Lymph Node Metastases: A Diagnostic Accuracy Meta-Analysis","volume":"47","author":"Tranoulis","year":"2021","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijsu.2018.05.010","article-title":"The Diagnostic Value of One Step Nucleic Acid Amplification (OSNA) in Differentiating Lymph Node Metastasis of Tumors: A Systematic Review and Meta-Analysis","volume":"56","author":"Zhou","year":"2018","journal-title":"Int. J. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/biomet\/80.1.27","article-title":"Bias Reduction of Maximum Likelihood Estimates","volume":"80","author":"Firth","year":"1993","journal-title":"Biometrika"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jclinepi.2016.02.031","article-title":"Adequate Sample Size for Developing Prediction Models Is Not Simply Related to Events per Variable","volume":"76","author":"Ogundimu","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sychowski, G., Romanowicz, H., and Smolarz, B. (2025). Application of the OSNA Technique (One-Step Nucleic Acid Amplification Test) in Breast Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020656"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s00423-025-03742-4","article-title":"Systematic Review and Meta-Analysis of Diagnostic Accuracy of One-Step Nucleic Acid Amplification for Lymph Node Metastases of Papillary Thyroid Carcinoma","volume":"410","author":"Rodrigo","year":"2025","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"M\u00e4rkl, B., Grosser, B., Bauer, K., Vlasenko, D., Schenkirsch, G., Probst, A., and Kriening, B. (2021). Ultrastaging Using Ex Vivo Sentinel Lymph Node Mapping and One-Step Nucleic Acid Amplification (OSNA) in Gastric Cancer: Experiences of a European Center. Cancers, 13.","DOI":"10.3390\/cancers13112683"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Diaz-Mercedes, S., Archilla, I., Lahoz, S., Rodrigo-Calvo, M.T., Lopez-Prades, S., Tarragona, J., Landolfi, S., Concha, A., Machado, I., and Maurel, J. (2022). Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage\u2014A Multicentre Study. Cancers, 14.","DOI":"10.3390\/cancers14246072"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rodrigo-Calvo, M.T., Saez De Gordoa, K., Lopez-Prades, S., Archilla, I., Diaz, A., Berrios, M., Camps, J., Musulen, E., and Cuatrecasas, M. (2023). Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15030842"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1007\/s00268-020-05949-6","article-title":"Molecular Lymph Node Staging with One-Step Nucleic Acid Amplification and its Prognostic Value for Patients with Colon Cancer: The First Follow-up Study","volume":"45","author":"Weixler","year":"2021","journal-title":"World J. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.dld.2017.05.017","article-title":"Molecular Analysis of Sentinel Lymph Node in Colon Carcinomas by One-Step Nucleic Acid Amplification (OSNA) Reduces Time to Adjuvant Chemotherapy Interval","volume":"49","author":"Marhic","year":"2017","journal-title":"Dig. Liver Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1016\/j.suronc.2011.05.001","article-title":"A Systematic Review of Cancer Related Patient Outcomes after Anterior Resection and Abdominoperineal Excision for Rectal Cancer in the Total Mesorectal Excision Era","volume":"20","author":"How","year":"2011","journal-title":"Surg. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Swedish Rectal Cancer Trial, Cedermark, B., Dahlberg, M., Glimelius, B., P\u00e5hlman, L., Rutqvist, L.E., and Wilking, N. (1997). Improved Survival with Preoperative Radiotherapy in Resectable Rectal Cancer. N. Engl. J. Med., 336, 980\u2013987.","DOI":"10.1056\/NEJM199704033361402"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"327","DOI":"10.20892\/j.issn.2095-3941.2017.0037","article-title":"Potential Predictive Factors for Pathologic Complete Response after the Neoadjuvant Treatment of Rectal Adenocarcinoma: A Single Center Experience","volume":"14","author":"Letaief","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2030097","DOI":"10.1001\/jamanetworkopen.2020.30097","article-title":"Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis","volume":"3","author":"Kasi","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1002\/ijc.31785","article-title":"An Overview of 25 Years of Incidence, Treatment and Outcome of Colorectal Cancer Patients","volume":"143","author":"Brouwer","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s00384-022-04121-x","article-title":"Right Colon, Left Colon, and Rectal Cancer Have Different Oncologic and Quality of Life Outcomes","volume":"37","author":"Duraes","year":"2022","journal-title":"Int. J. Color. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.clon.2015.11.004","article-title":"Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy","volume":"28","author":"Boustani","year":"2016","journal-title":"Clin. Oncol. R. Coll. Radiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"103627","DOI":"10.1016\/j.critrevonc.2022.103627","article-title":"Adjuvant Chemotherapy after Neoadjuvant Chemo-Radiotherapy and Surgery in Locally Advanced Rectal Cancer. A Systematic Review of Literature with a Meta-Analysis of Randomized Clinical Trials","volume":"172","author":"Tamburini","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/CCO.0000000000000641","article-title":"Adjuvant Chemotherapy in Rectal Cancer: State of the Art and Future Perspectives","volume":"32","author":"Glimelius","year":"2020","journal-title":"Curr. Opin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101948","DOI":"10.1016\/j.ctrv.2019.101948","article-title":"Adjuvant Chemotherapy for Rectal Cancer: Current Evidence and Recommendations for Clinical Practice","volume":"83","author":"Bregni","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Quasar Collaborative Group (2007). Adjuvant Chemotherapy versus Observation in Patients with Colorectal Cancer: A Randomised Study. Lancet, 370, 2020\u20132029.","DOI":"10.1016\/S0140-6736(07)61866-2"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00384-022-04096-9","article-title":"Oxaliplatin-Based Adjuvant Chemotherapy Rather than Fluorouracil-Based Chemotherapy in Rectal Cancer Is More Efficient to Decrease Distant Metastasis and Increase Survival after Preoperative Chemoradiotherapy and Surgery: A Meta-Analysis","volume":"37","author":"Song","year":"2022","journal-title":"Int. J. Color. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00384-018-3181-9","article-title":"Is Adjuvant Chemotherapy Necessary for Locally Advanced Rectal Cancer Patients with Pathological Complete Response after Neoadjuvant Chemoradiotherapy and Radical Surgery? A Systematic Review and Meta-Analysis","volume":"34","author":"Ma","year":"2019","journal-title":"Int. J. Color. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Japanese Study Group for Postoperative Follow-up of Colorectal Cancer, Ahiko, Y., Shida, D., Kudose, Y., Nakamura, Y., Moritani, K., Yamauchi, S., Sugihara, K., and Kanemitsu, Y. (2021). Recurrence Hazard of Rectal Cancer Compared with Colon Cancer by Adjuvant Chemotherapy Status: A Nationwide Study in Japan. J. Gastroenterol., 56, 371\u2013381.","DOI":"10.1007\/s00535-021-01771-6"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Marano, L., Verre, L., Carbone, L., Poto, G.E., Fusario, D., Venezia, D.F., Calomino, N., Ka\u017amierczak-Siedlecka, K., Polom, K., and Marrelli, D. (2023). Current Trends in Volume and Surgical Outcomes in Gastric Cancer. J. Clin. Med., 12.","DOI":"10.3390\/jcm12072708"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6039","DOI":"10.1002\/cncr.27667","article-title":"Molecular Investigation of Lymph Nodes in Colon Cancer Patients Using One-Step Nucleic Acid Amplification (OSNA): A New Road to Better Staging?","volume":"118","author":"Zettl","year":"2012","journal-title":"Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1158\/1078-0432.CCR-15-2199","article-title":"Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial","volume":"22","author":"Yamamoto","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1200\/JCO.2010.34.3426","article-title":"Adjuvant Chemotherapy for Stage II Colon Cancer with Poor Prognostic Features","volume":"29","author":"Greenblatt","year":"2011","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/13\/2141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:58:42Z","timestamp":1760032722000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/13\/2141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,25]]},"references-count":71,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cancers17132141"],"URL":"https:\/\/doi.org\/10.3390\/cancers17132141","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2025,6,25]]}}}