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The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment | Anticancer Research
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//cdn.jsdelivr.net" /> <link rel="dns-prefetch" href="//cdn.foxycart.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <link rel="canonical" href="https://ar.iiarjournals.org/content/44/11/5035" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/44/11/5035.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/44/11/5035.full.txt" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/44/11/5035.ppt" /> <meta name="issue_cover_image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/44/11.cover-source.jpg" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/anticanres/44/11/5035.atom" /> <meta name="HW.pisa" content="anticanres;44/11/5035" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment" /> <meta name="DC.Identifier" content="10.21873/anticanres.17327" /> <meta name="DC.Date" content="2024-11-01" /> <meta name="DC.Publisher" content="International Institute of Anticancer Research" /> <meta name="DC.Rights" content="Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0)." /> <meta name="DC.AccessRights" content="open-access" /> <meta name="DC.Description" content="Background/Aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm3) × platelet count (cell/mm3 ×103)/lymphocyte count (cell/mm3). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC." /> <meta name="DC.Contributor" content="RYUKI ESASHI" /> <meta name="DC.Contributor" content="TORU AOYAMA" /> <meta name="DC.Contributor" content="YUKIO MAEZAWA" /> <meta name="DC.Contributor" content="ITARU HASHIMOTO" /> <meta name="DC.Contributor" content="SOSUKE YAMAMOTO" /> <meta name="DC.Contributor" content="MAMORU UCHIYAMA" /> <meta name="DC.Contributor" content="KOJI NUMATA" /> <meta name="DC.Contributor" content="SHINNOSUKE KAWAHARA" /> <meta name="DC.Contributor" content="KEISUKE KAZAMA" /> <meta name="DC.Contributor" content="AYAKO TAMAGAWA" /> <meta name="DC.Contributor" content="AYA SAITO" /> <meta name="DC.Contributor" content="NORIO YUKAWA" /> <meta name="article:published_time" content="2024-11-01" /> <meta name="article:section" content="Clinical Studies" /> <meta name="citation_title" content="The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment" /> <meta name="citation_abstract" lang="en" content="<p>Background/Aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm<sup>3</sup>) × platelet count (cell/mm<sup>3</sup> ×10<sup>3</sup>)/lymphocyte count (cell/mm<sup>3</sup>). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p&lt;0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC.</p>" /> <meta name="citation_journal_title" content="Anticancer Research" /> <meta name="citation_publisher" content="International Institute of Anticancer Research" /> <meta name="citation_publication_date" content="2024/11/01" /> <meta name="citation_mjid" content="anticanres;44/11/5035" /> <meta name="citation_id" content="44/11/5035" /> <meta name="citation_public_url" content="https://ar.iiarjournals.org/content/44/11/5035" /> <meta name="citation_abstract_html_url" content="https://ar.iiarjournals.org/content/44/11/5035.abstract" /> <meta name="citation_full_html_url" content="https://ar.iiarjournals.org/content/44/11/5035.full" /> <meta name="citation_pdf_url" content="https://ar.iiarjournals.org/content/anticanres/44/11/5035.full.pdf" /> <meta name="citation_issn" content="0250-7005" /> <meta name="citation_issn" content="1791-7530" /> <meta name="citation_doi" content="10.21873/anticanres.17327" /> <meta name="citation_pmid" content="39477307" /> <meta name="citation_volume" content="44" /> <meta name="citation_issue" content="11" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Clinical Studies" /> <meta name="citation_firstpage" content="5035" /> <meta name="citation_lastpage" content="5041" /> <meta name="citation_access" content="all" /> <meta name="citation_author" content="RYUKI ESASHI" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author_email" content="ryukiesashi@gmail.com" /> <meta name="citation_author" content="TORU AOYAMA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author_email" content="t-aoyama@lilac.plala.or.jp" /> <meta name="citation_author" content="YUKIO MAEZAWA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="ITARU HASHIMOTO" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="SOSUKE YAMAMOTO" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="MAMORU UCHIYAMA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="KOJI NUMATA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="SHINNOSUKE KAWAHARA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="KEISUKE KAZAMA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="AYAKO TAMAGAWA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="AYA SAITO" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_author" content="NORIO YUKAWA" /> <meta name="citation_author_institution" content="Department of Surgery, Yokohama City University, Yokohama, Japan" /> <meta name="citation_reference" content="citation_journal_title=CA Cancer J Clin;citation_author=F. 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Shoda;citation_author=H. Akaike;citation_author=N. Hosomura;citation_author=H. Amemiya;citation_author=H. Kawaida;citation_author=M. Sudoh;citation_author=H. Kono;citation_author=D. Ichikawa;citation_title=Prognostic value of preoperative psoas muscle index as a measure of nutritional status in patients with esophageal cancer receiving neoadjuvant therapy;citation_pages=111232;citation_volume=90;citation_year=2021;citation_pmid=33964490;citation_doi=10.1016/j.nut.2021.111232" /> <meta name="citation_fulltext_world_readable" content="" /> <meta name="twitter:title" content="The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/44/11.cover-source.jpg" /> <meta name="twitter:description" content="Background/Aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm3) × platelet count (cell/mm3 ×103)/lymphocyte count (cell/mm3). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC." /> <meta name="og-title" property="og:title" content="The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment" /> <meta name="og-url" property="og:url" content="https://ar.iiarjournals.org/content/44/11/5035" /> <meta name="og-site-name" property="og:site_name" content="Anticancer Research" /> <meta name="og-description" property="og:description" content="Background/Aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm3) × platelet count (cell/mm3 ×103)/lymphocyte count (cell/mm3). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/44/11.cover-source.jpg" /> <link rel="shortlink" href="/node/81996" /> <link rel="shortcut icon" href="https://ar.iiarjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <title>The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment | Anticancer Research</title> <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__QEy_BpbtMcsqv3xURK855GSs2fFjOibU10yA758Mn4c__NucWi_bEk5E3BNVDtTt2nhiPtE1A5I24YwRDQ2fojJ0__M8F9fri-b1QX8RwJbNRiWvN_bqCXCQEG9-9ZZDMJpyg.css" media="all" /> <link type="text/css" rel="stylesheet" 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class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a"> <div class="highwire-cite-overline"><span class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Clinical Studies</span></span></div> <div class="highwire-cite-access"><span class="highwire-citation-access"><i class="highwire-access-icon highwire-access-icon-open-access open-access hw-icon-open-access" title="Open Access" aria-hidden="true"></i><span class="element-invisible highwire-access-icon highwire-access-icon-open-access" style="">Open Access</span></span></div> <h1 class="highwire-cite-title" id="page-title">The Clinical Impact of the Systemic Immune-inflammation Index in Esophageal Cancer Patients Receiving Curative Treatment</h1> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">RYUKI ESASHI</span>, <span class="highwire-citation-author" data-delta="1">TORU AOYAMA</span>, <span class="highwire-citation-author" data-delta="2">YUKIO MAEZAWA</span>, <span class="highwire-citation-author" data-delta="3">ITARU HASHIMOTO</span>, <span class="highwire-citation-author" data-delta="4">SOSUKE YAMAMOTO</span>, <span class="highwire-citation-author" data-delta="5">MAMORU UCHIYAMA</span>, <span class="highwire-citation-author" data-delta="6">KOJI NUMATA</span>, <span class="highwire-citation-author" data-delta="7">SHINNOSUKE KAWAHARA</span>, <span class="highwire-citation-author" data-delta="8">KEISUKE KAZAMA</span>, <span class="highwire-citation-author" data-delta="9">AYAKO TAMAGAWA</span>, <span class="highwire-citation-author" data-delta="10">AYA SAITO</span> and <span class="highwire-citation-author" data-delta="11">NORIO YUKAWA</span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">November 2024, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">44 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">5035-5041; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.21873/anticanres.17327 </span></div> <div class="highwire-cite-extras"><span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Add to Cart (%short-price)" data-apath="/anticanres/44/11/5035.atom" data-type="link" data-font-icon="" data-parent-id="81985"></span></div> </div> <div id="hw-article-author-popups-top-node-81996--61217311206" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">RYUKI ESASHI </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>Department of Surgery, Yokohama City University, Yokohama, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=RYUKI%2BESASHI%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=ESASHI%20R&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ARYUKI%2BESASHI%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:ryukiesashi@gmail.com" class="" data-icon-position="" data-hide-link-title="0">ryukiesashi@gmail.com</a></span></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">TORU AOYAMA </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'>Department of Surgery, Yokohama City University, Yokohama, Japan</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=TORU%2BAOYAMA%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=AOYAMA%20T&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li 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class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="https://ar.iiarjournals.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-jnl_iiar_tab_art"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-markup" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article fulltext-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><p id="p-5">Background/Aim: The systemic immune-inflammation index (SII) is a calculated biomarker developed to predict the prognosis of malignant tumors. This study evaluated the influence of the SII in patients with esophageal cancer (EC) who underwent curative resection. Patients and Methods: Patients who underwent radical esophagectomy and lymph node dissection for EC were enrolled. The SII was calculated as follows: neutrophil count (cell/mm<sup>3</sup>) × platelet count (cell/mm<sup>3</sup> ×10<sup>3</sup>)/lymphocyte count (cell/mm<sup>3</sup>). The SII, patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were assessed. Results: A total of 180 patients were included in this study. The cutoff value of the SII was set at 500 according to previous studies. Of the 180 patients, 100 were classified into the SII-high group and 80 into the SII-low group. The 3- and 5-year OS rates were 59.0% and 54.0%, respectively, in the SII-high group and 80.0% and 75.0%, respectively, in the SII-low group, showing significant differences between the groups (p=0.001). A multivariate analysis for the OS demonstrated that the SII was an independent prognostic factor (hazard ratio=2.333, 95% confidence interval=1.411-3.860, p<0.001), with similar results obtained for the RFS. Furthermore, hematological recurrence was significantly higher in the SII-high group than in the SII-low group (36.0% vs. 17.5%, p=0.006). Conclusion: The preoperative SII was an independent prognostic factor for OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC.</p></div><span class="kwd-group-title">Key Words:</span><ul class="kwd-group"><li class="kwd"><a href="/keyword/systemic-immune-inflammation-index-sii" class="hw-term hw-article-keyword hw-article-keyword-systemic-immune-inflammation-index-sii" rel="nofollow">Systemic Immune-inflammation Index (SII)</a></li><li class="kwd"><a href="/keyword/esophageal-cancer" class="hw-term hw-article-keyword hw-article-keyword-esophageal-cancer" rel="nofollow">esophageal cancer</a></li><li class="kwd"><a href="/keyword/prognostic-biomarker" class="hw-term hw-article-keyword hw-article-keyword-prognostic-biomarker" rel="nofollow">prognostic biomarker</a></li><li class="kwd"><a href="/keyword/overall-survival" class="hw-term hw-article-keyword hw-article-keyword-overall-survival" rel="nofollow">overall survival</a></li><li class="kwd"><a href="/keyword/recurrence-free-survival" class="hw-term hw-article-keyword hw-article-keyword-recurrence-free-survival" rel="nofollow">recurrence-free survival</a></li></ul><p id="p-6">Esophageal cancer (EC) is the seventh leading cause of cancer-related death worldwide and was responsible for 445,000 deaths in 2022 (<a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1</a>). Despite improvements in the ability to detect early-stage EC, many EC patients are diagnosed at a late stage with metastasis (<a id="xref-ref-2-1" class="xref-bibr" href="#ref-2">2</a>). In addition, despite advances in surgery, chemoradiotherapy, and targeted therapy, the prognosis of patients with EC remains poor because of early recurrence or distant metastasis (<a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3</a>). The 5-year overall survival (OS) rate is reported to be approximately 10%-20% (<a id="xref-ref-4-1" class="xref-bibr" href="#ref-4">4</a>-<a id="xref-ref-6-1" class="xref-bibr" href="#ref-6">6</a>). The identification of valuable, non-invasive, and easily available prognostic factors that can lead to individualized treatment and an improved prognosis is thus crucial (<a id="xref-ref-3-2" class="xref-bibr" href="#ref-3">3</a>, <a id="xref-ref-7-1" class="xref-bibr" href="#ref-7">7</a>).</p><p id="p-7">Accumulating evidence has shown that inflammatory responses and the immune system play a role in tumor development, invasion, and metastasis (<a id="xref-ref-8-1" class="xref-bibr" href="#ref-8">8</a>). Several inflammation-based markers are associated with treatment response and prognosis in EC patients, such as the serum neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) (<a id="xref-ref-9-1" class="xref-bibr" href="#ref-9">9</a>). The SII, calculated as “(platelet count × neutrophil count)/lymphocyte count” (<a id="xref-ref-7-2" class="xref-bibr" href="#ref-7">7</a>), predicts the prognosis of malignant tumors, such as hepatocellular carcinoma, rectal cancer, gastric cancer, pancreatic cancer and lung cancer, and is superior to the NLR and PLR as a prognostic factor in these diseases (<a id="xref-ref-10-1" class="xref-bibr" href="#ref-10">10</a>-<a id="xref-ref-19-1" class="xref-bibr" href="#ref-19">19</a>). If the SII can be established as a useful predictive marker of the prognosis of EC patients as well, it will be possible to determine the optimal treatment of EC depending on the SII.</p><p id="p-8">In the present study, we evaluated the relationship between the SII and the prognosis of patients with EC who underwent curative resection at a single high-volume center in Japan.</p><div class="section patients-methods" id="sec-1"><h2 class="">Patients and Methods</h2><p id="p-9"><em>Patients</em>. Consecutive patients who had undergone esophagectomy for EC at Yokohama City University between 2008 and 2022 were screened. Patients who met the following inclusion criteria were enrolled in this study: 1) histologically confirmed EC (including squamous cell carcinoma, adenosquamous cell carcinoma, and adenocarcinoma); 2) clinical stage I-III disease, defined according to the 12th edition of the Japanese Classification of Esophageal Cancer; 3) curative esophagectomy for EC; and 4) complete resection (R0) of EC with radical lymph node dissection. The patient characteristics, cancer profiles (tumor site, pathological findings, TNM classification), and laboratory data were collected from the medical records.</p><p id="p-10"><em>Patient management</em>. All patients in the present study underwent curative esophagectomy with either two- or three-field lymphatic dissection considering the tumor site. In principle, all patients with a clinical T2 or T3 status underwent neoadjuvant chemotherapy. Chemotherapy regimens were selected from 5-fluorouracil and platinum agent (FP) or 5-fluorouracil, platinum agent, and docetaxel regimen (DCF) according to the patient’s cancer progression and background. Follow-up evaluations after surgery were performed in outpatient clinics. In principle, patients underwent hematological tests (including tumor marker measurements) and physical examinations at least every three months for a duration of five years. Furthermore, patients underwent computed tomography (CT) every three months within the initial three years post-surgery, followed by semi-annual CT up to the fifth year after surgery.</p><p id="p-11"><em>The Systemic Immune-Inflammation Index (SII)</em>. The SII was calculated as follows: neutrophil count (cell/mm<sup>3</sup>) × platelet count (cell/mm<sup>3</sup> ×10<sup>3</sup>)/lymphocyte count (cell/mm<sup>3</sup>). Blood cell counts were collected from the medical records prior to surgery.</p><p id="p-12"><em>Statistical analyses</em>. The significance of differences between the SII and clinicopathological factors was evaluated using the chi-square test and Mann–Whitney test, and the Kaplan–Meier method was used to generate curves for the OS and recurrence-free survival (RFS). A Cox proportional hazards model was used for the univariate and multivariate survival analyses. Statistical significance was set at <em>p</em><0.05. The SPSS software program (v27.0 J Win; IBM, Armonk, NY, USA) was used to perform all statistical analyses.</p><p id="p-13"><em>Ethical approval</em>. Approval for the present study was obtained from the Institutional Review Board of Yokohama City University (approval number: F220500064).</p></div><div class="section results" id="sec-2"><h2 class="">Results</h2><p id="p-14"><em>Patient characteristics</em>. A total of 180 patients were enrolled in the present study, of whom 155 were men and 25 women. The mean patient age was 69 years old. When comparing the OS and each clinicopathological characteristic, there were significant differences in the T status, lymph node metastasis, lymphovascular invasion, and SII (<a id="xref-table-wrap-1-1" class="xref-table" href="#T1">Table I</a>). Based on the three- and five-year survival rates and previous studies, we set the cutoff value of the SII to 500 in the present study. Of the 180 patients, 100 and 80 were allocated to the SII-high and SII-low groups, respectively.</p><div id="T1" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/82300/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/82300/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82300" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table I.</span> <p id="p-15" class="first-child">Comparison of survival rates stratified by patient characteristics.</p><div class="sb-div caption-clear"></div></div></div><p id="p-16"><em>Survival analyses</em>. The five-year OS rate was 54.0% in the SII-high group, and 75.0% in the SII-low group (<a id="xref-fig-1-1" class="xref-fig" href="#F1">Figure 1</a>), showing significant differences between the groups (<em>p</em>=0.001). A univariate analysis of the OS showed that the T status, lymph node metastasis, lymphovascular invasion, and SII were selected as prognostic factors. A multivariate analysis for the OS demonstrated that the T status, lymph node metastasis, and SII were independent prognostic factors [hazard ratio (HR)=2.333; 95% confidence interval (CI)=1.411-3.860, <em>p</em><0.001] (<a id="xref-table-wrap-2-1" class="xref-table" href="#T2">Table II</a>).</p><div id="F1" class="fig pos-float odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F1.large.jpg?width=800&height=600&carousel=1" title="The overall survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1162717939" data-figure-caption="<div class="highwire-markup">The overall survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups.</div>" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Figure 1." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F1.medium.gif" width="440" height="246"/><noscript><img class="highwire-fragment fragment-image" alt="Figure 1." src="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F1.medium.gif" width="440" height="246"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F1.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Figure 1." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F1.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82290" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption" xmlns:xhtml="http://www.w3.org/1999/xhtml"><span class="fig-label">Figure 1.</span> <p id="p-17" class="first-child">The overall survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups.</p><div class="sb-div caption-clear"></div></div></div><div id="T2" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/82237/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/82237/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82237" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table II.</span> <p id="p-18" class="first-child">Univariate and Multivariate Cox proportional hazards analysis of clinicopathological factors for overall survival.</p><div class="sb-div caption-clear"></div></div></div><p id="p-19">The five-year RFS rates were 38.0% in the SII-high group and 56.25% in the SII-low group (<a id="xref-fig-2-1" class="xref-fig" href="#F2">Figure 2</a>), showing significant differences between the groups (<em>p</em><0.001). A univariate analysis of the RFS showed that the T status, lymph node metastasis, lymphovascular invasion, and SII were selected as prognostic factors. A multivariate analysis of the RFS demonstrated that the T status, lymph node metastasis, lymphovascular invasion, and SII were significant prognostic factors (HR=2.197, 95%CI=1.414-3.413, <em>p</em><0.001) (<a id="xref-table-wrap-3-1" class="xref-table" href="#T3">Table III</a>). <em>Recurrence site</em>. When comparing the recurrence sites between the groups, the percentage of hematological recurrence was significantly higher in the SII-high group than in the SII-low group (hematological recurrence: 36.0% <em>vs</em>. 17.5%, <em>p</em>=0.006) (<a id="xref-table-wrap-4-1" class="xref-table" href="#T4">Table IV</a>).</p><div id="F2" class="fig pos-float odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F2.large.jpg?width=800&height=600&carousel=1" title="The recurrence-free survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1162717939" data-figure-caption="<div class="highwire-markup">The recurrence-free survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups.</div>" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Figure 2." src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F2.medium.gif" width="440" height="255"/><noscript><img class="highwire-fragment fragment-image" alt="Figure 2." src="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F2.medium.gif" width="440" height="255"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F2.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Figure 2." data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="https://ar.iiarjournals.org/content/anticanres/44/11/5035/F2.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82021" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div><div class="fig-caption"><span class="fig-label">Figure 2.</span> <p id="p-20" class="first-child">The recurrence-free survival of esophageal cancer patients in the systemic immune-inflammation index (SII) >500 and SII ≤500 groups.</p><div class="sb-div caption-clear"></div></div></div><div id="T3" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/82329/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/82329/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82329" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table III.</span> <p id="p-21" class="first-child">Univariate and Multivariate Cox proportional hazards analysis of clinicopathological factors for recurrence-free survival.</p><div class="sb-div caption-clear"></div></div></div><div id="T4" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/82177/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/82177/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82177" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table IV.</span> <p id="p-22" class="first-child">Patterns of recurrence according to systemic immune-inflammation index.</p><div class="sb-div caption-clear"></div></div></div><p id="p-23"><em>Perioperative clinical status</em>. There were significant differences in the preoperative body mass index (BMI), serum hemoglobin (Hb), total protein (TP), albumin, C-reactive protein (CRP), SCC, CYFRA, and psoas muscle index (PMI), which was calculated by dividing the total psoas muscle area (mm<sup>2</sup>) by the square of the height (m), between the SII-high and SII-low groups. In addition, more patients in the SII-high group received preoperative enteral nutrition than in the SII-low group (<a id="xref-table-wrap-5-1" class="xref-table" href="#T5">Table V</a>).</p><div id="T5" class="table pos-float"><div class="table-inline table-callout-links"><div class="callout"><span>View this table:</span><ul class="callout-links"><li class="view-inline first"><a href="" class="table-expand-inline" data-table-url="/highwire/markup/82175/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&table-expand-inline=1" data-icon-position="" data-hide-link-title="0">View inline</a></li><li class="view-popup"><a href="/highwire/markup/82175/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed" class="colorbox colorbox-load table-expand-popup" rel="gallery-fragment-tables" data-icon-position="" data-hide-link-title="0">View popup</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/82175" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><div class="table-caption"><span class="table-label">Table V.</span> <p id="p-24" class="first-child">Perioperative clinical status according to systemic immune-inflammation index.</p><div class="sb-div caption-clear"></div></div></div></div><div class="section discussion" id="sec-3"><h2 class="">Discussion</h2><p id="p-25">The present study investigated the value of the SII as a predictive marker of prognosis in patients with EC who underwent curative resection. The major finding was that the SII was an independent prognostic factor for the OS and RFS. In addition, it has been shown that more hematological metastases occur in patients with a high SII than in those with a low SII. Our results suggest that a high SII can predict a poor prognosis.</p><p id="p-26">In the present study, the five-year OS and RFS rates were 54.0% and 38.0% in the SII-high group, respectively, and 75.0% and 56.25% in the SII-low group, respectively, showing significant differences between the groups (<em>p</em>=0.001 for the OS and <em>p</em><0.001 for the RFS). Furthermore, the SII was an independent prognostic factor for the OS (HR=2.333, 95%CI= 1.411-3.860, <em>p</em><0.001) and RFS (HR=2.197, 95%CI=1.414-3.413, <em>p</em><0.001) in a multivariate analysis. Similar results have been reported in previous studies. Gao <em>et al.</em> demonstrated the prognostic effect of the SII in 468 patients with esophageal squamous cell carcinoma (ESCC) who underwent curative esophagectomy with R0 resection (<a id="xref-ref-20-1" class="xref-bibr" href="#ref-20">20</a>). Patients were divided into SII-high (n=325) and SII-low (n=143) groups based on a cutoff value of 479.72 in that study. In the multivariate analysis, the SII was selected as an independent prognostic factor for the OS (HR=1.64, 95%CI=1.247-2.063, <em>p</em><0.001) and disease-free survival (DFS) (HR=1.681; 95%CI=1.307-2.162, <em>p</em><0.001). In another study, Obata <em>et al.</em> evaluated the clinical significance of the preoperative SII in predicting the long-term outcomes of patients who received neoadjuvant therapy for ESCC (<a id="xref-ref-19-2" class="xref-bibr" href="#ref-19">19</a>). Two hundred and seventy-seven ESCC patients were enrolled in the study, and patients were distributed to the SII-high group (n=79) and SII-low group (n=198) using a cutoff value of 700. The five-year RFS rates of the SII-high and SII-low patients were 43.0% and 59.5%, respectively (<em>p</em>=0.0087). Furthermore, a multivariate analysis identified the preoperative SII as an independent prognostic factor for the RFS (HR=1.55, 95%CI=1.06-2.28, <em>p</em>=0.0229). The authors concluded that the preoperative SII was associated with an adverse prognosis in patients with ESCC who underwent curative resection after neoadjuvant therapy.</p><p id="p-27">Some factors were estimated to affect the SII status and survival rate of EC patients in the present study. First, the preoperative nutritional status of the patients was poorer in the SII-high group than in the SII-low group. EC patients in the SII-high group had low serum albumin levels (SII-high and SII-low: 3.92 and 4.17, respectively, <em>p</em><0.001), BMI (20.92 and 21.82, respectively, <em>p</em>=0.014), and PMI (4.73 and 5.16, respectively, <em>p</em>=0.038). Some previous studies have suggested that a poor nutritional status is unfavorable for EC patients. Gu showed that the pretreatment BMI was an independent prognostic factor (HR=0.829; 95%CI=0.711-0.966, <em>p</em>=0.017), and the 10-year OS in EC patients with a high BMI was significantly longer than that in patients with a low BMI (<em>p</em>=0.004) (<a id="xref-ref-21-1" class="xref-bibr" href="#ref-21">21</a>). Nakayama <em>et al.</em> detected significant differences in the five-year OS (55.3% and 47.5%, <em>p</em>=0.045) and the progressive-free survival (56.1% and 43.2%, <em>p</em>=0.043) in EC patients with high and low preoperative PMI values (<a id="xref-ref-22-1" class="xref-bibr" href="#ref-22">22</a>). Second, hematological recurrence was more frequent in the SII-high group than in the SII-low group (36.0% <em>vs</em>. 17.5%, <em>p</em>=0.006) in the present study. Few studies have described the relationship between SII and recurrence sites of EC. Obata <em>et al.</em> showed that preoperative SII was significantly associated with the prevalence of hematogenous recurrence (SII-high and SII-low: 28.3% and 14.7%, respectively; <em>p</em>=0.0118) (<a id="xref-ref-20-2" class="xref-bibr" href="#ref-20">20</a>). These results indicate that a high SII predicts circulating micrometastasis and results in a poor prognosis.</p><p id="p-28">This study was designed as a single-center retrospective analysis, thus there may be some bias in the patient background, treatment, and surgical technique. In addition, we set the cutoff value of the SII at 500 in the present study, but previous studies set various cutoff values, such as 307 in the study by Zhang <em>et al.</em>, 700 in the study by Obata <em>et al.</em>, and 479.72 in the study by Gao <em>et al.</em> The study design, which included the patient background characteristics, patient number, and methods used for determining the cutoff value of the SII, could have affected these differences (<a id="xref-ref-3-3" class="xref-bibr" href="#ref-3">3</a>, <a id="xref-ref-19-3" class="xref-bibr" href="#ref-19">19</a>, <a id="xref-ref-20-3" class="xref-bibr" href="#ref-20">20</a>). Considering these points, our study needs to be validated in a larger cohort, and further studies will be required to determine the optimal cutoff value of the SII.</p></div><div class="section conclusion" id="sec-4"><h2 class="">Conclusion</h2><p id="p-29">The preoperative SII was found to be an independent prognostic factor for the OS and RFS in patients with EC who underwent curative resection. Thus, the SII can be a useful marker for the treatment and management of EC.</p></div><div class="section ack" id="ack-1"><h2 class="">Acknowledgements</h2><p id="p-34">This study was supported in part by the nonprofit organization of Yokohama Surgical Research Group (YSRG).</p></div><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn" id="fn-2"><p id="p-2"><strong>Authors’ Contributions</strong></p><p id="p-3">RE and TA contributed substantially to the concept and study design. TA, IH, YE, SY, MU, KN, KK, SK, and AT made substantial contributions to the data acquisition, analysis, and interpretation. TA, AS, IH, YM, and NY were involved in drafting and critically revising the manuscript for important intellectual content. TA and RE approved the final version of the manuscript.</p></li><li class="fn" id="fn-3"><p id="p-30"><strong>Conflicts of Interest</strong></p><p id="p-31">The Authors declare no conflicts of interest in association with the present study.</p></li><li class="fn" id="fn-4"><p id="p-32"><strong>Funding</strong></p><p id="p-33">No funding was received for conducting this study.</p></li></ul></div><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2024-09-10"><span class="received-label">Received </span>September 10, 2024.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2024-09-20"><span class="rev-recd-label">Revision received </span>September 20, 2024.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2024-09-23"><span class="accepted-label">Accepted </span>September 23, 2024.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</li></ul><div class="license" id="license-1"><p id="p-4">This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (<a href="https://creativecommons.org/licenses/by-nc-nd/4.0" rel="license">https://creativecommons.org/licenses/by-nc-nd/4.0</a>).</p></div><div class="section ref-list" id="ref-list-1"><h2 class="">References</h2><ol class="cit-list"><li><a class="rev-xref-ref" href="#xref-ref-1-1" title="View reference 1 in text" id="ref-1">↵</a><div class="cit ref-cit ref-journal" id="cit-44.11.5035.1" data-doi="10.3322/caac.21834"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Bray</span> <span class="cit-name-given-names">F</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Laversanne</span> <span class="cit-name-given-names">M</span></span>, </li><li><span 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id="cit-44.11.5035.21" data-doi="10.2147/CMAR.S197820"><div class="cit-metadata"><ol class="cit-auth-list"><li><span class="cit-auth"><span class="cit-name-surname">Gu</span> <span class="cit-name-given-names">WS</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Fang</span> <span class="cit-name-given-names">WZ</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Liu</span> <span class="cit-name-given-names">CY</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Pan</span> <span class="cit-name-given-names">KY</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Ding</span> <span class="cit-name-given-names">R</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Li</span> <span class="cit-name-given-names">XH</span></span>, </li><li><span class="cit-auth"><span class="cit-name-surname">Duan</span> <span 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class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">AYAKO</span> <span class="nlm-surname">TAMAGAWA</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">AYA</span> <span class="nlm-surname">SAITO</span></span>, <span class="highwire-citation-author" data-delta="11"><span class="nlm-given-names">NORIO</span> <span class="nlm-surname">YUKAWA</span></span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-oa-ind highwire-cite-metadata"><i class="highwire-oa-indicator"></i> </span><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">Nov 2024, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">44 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">5035-5041; 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