{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:09:56Z","timestamp":1777489796318,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold><jats:italic>Ex vivo<\/jats:italic> methylene blue (MB) injection into the main supplying arteries of the colorectal specimen after surgical removal is an uncomplicated technique to support lymph node harvest during pathological evaluation. The primary aim of this randomized, interventional, bicentric trial was to evaluate the impact of MB injection on lymph node yield, with secondary aims assessing the accuracy of lymph node staging and the effect on 5-year overall survival for patients undergoing resection of colorectal cancer.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In the study period between December 2013 and August 2015, 200 colorectal resections were performed at two independent onco-surgery centers of Hungary. Following surgical resection, each specimen was randomly assigned either to the control (standard pathological work-up) or to the MB staining group before formaldehyde fixation. Patient-level surgical and clinical data were retrieved from routinely collected clinical datasets. Survival status data were obtained from the National Health Insurance Fund of Hungary.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 162 specimens, 82 in the control and 80 in the MB groups, were included for analysis. Baseline characteristics were equally distributed among study groups, except for specimen length. Both the median of total number of lymph nodes retrieved (control 11 \u00b1 8 [0\u201333] nodes vs. MB 14 \u00b1 6 [0\u201342] nodes; <jats:italic>p<\/jats:italic> &amp;lt; 0.01), and the ratio of cases with at least 12 removed lymph nodes (36\/82, 43.9% vs. 53\/80, 66.3%; <jats:italic>p<\/jats:italic> &amp;lt; 0.01) were higher in the MB group. The rate of accurate lymph node staging was non-significantly improved. As for rectal cancer, nodal staging accuracy (16\/31, 51.6% vs. 23\/30, 76.7%; <jats:italic>p<\/jats:italic> = 0.04) and the proportion with minimum 12 lymph node retrieval (7\/31, 22.6%, vs. 18\/30, 60%; <jats:italic>p<\/jats:italic> &amp;lt; 0.01) was improved by MB injection. In Mantel\u2013Cox regression, a statistically significant survival benefit with methylene blue injection at 5\u00a0years post-surgery was proven (51.2% vs. 68.8%; <jats:italic>p<\/jats:italic> = 0.04).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In our experience, postoperative <jats:italic>ex vivo<\/jats:italic> arterial methylene blue injection appears to be an uncomplicated technique, improving lymph node yield and decreasing the chance of insufficient nodal staging. The technique might also associate with a 5-year overall survival benefit.<\/jats:p>","DOI":"10.3389\/pore.2022.1610742","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T15:19:53Z","timestamp":1666106393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Improved Accuracy of Lymph Node Staging and Long-Term Survival Benefit in Colorectal Cancer With Ex Vivo Arterial Methylene Blue Infiltration"],"prefix":"10.3389","volume":"28","author":[{"given":"N\u00f3ra","family":"Suszt\u00e1k","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Beszny\u00e1k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e1lm\u00e1n","family":"Alm\u00e1si","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Bursics","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Kelemen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Borowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bal\u00e1zs","family":"B\u00e1nky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"B1","unstructured":"Estimated Number of Deaths Worldwide, Both Sexes, All Ages (Graph)2021"},{"key":"B2","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/jso.21226","article-title":"Clinically Important Aspects of Lymph Node Assessment in colon Cancer","volume":"99","author":"Wright","year":"2009","journal-title":"J Surg Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1463-1318.2008.01735.x","article-title":"Standardized Surgery for Colonic Cancer: Complete Mesocolic Excision and central Ligation-Ttechnical Notes and Outcome","volume":"11","author":"Hohenberger","year":"2009","journal-title":"Colorectal Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1053\/ejso.1999.0659","article-title":"Improved Survival and Local Control after Total Mesorectal Excision or D3 Lymphadenectomy in the Treatment of Primary Rectal Cancer: an International Analysis of 1411 Patients","volume":"25","author":"Havenga","year":"1999","journal-title":"Eur J Surg Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.3390\/cancers3021622","article-title":"Predictive and Prognostic Factors in Colorectal Cancer: a Personalized Approach","volume":"3","author":"Kulendran","year":"2011","journal-title":"Cancers (Basel)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1200\/JCO.2003.05.062","article-title":"Colon Cancer Survival Is Associated with Increasing Number of Lymph Nodes Analyzed: a Secondary Survey of Intergroup Trial INT-0089","volume":"21","author":"Le Voyer","year":"2003","journal-title":"J Clin Oncol"},{"key":"B7","article-title":"TNM Classification of Malignant Tumours","volume-title":"7th Ed. 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