{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:55:40Z","timestamp":1791363340374,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Direct tumour\u2010adipocyte interaction at the invasion front, termed Stroma AReactive Invasion Front Areas (SARIFA), has recently emerged as a novel H&amp;E\u2010based biomarker in colorectal cancer (CRC). SARIFA positivity is defined by a direct tumour\u2013adipocyte contact (TAC) without intervening stroma or inflammatory infiltrate. We performed a focused evidence synthesis of all published studies and a meta\u2010analysis to summarize the evidence on the prognostic value of TAC\/SARIFA in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Eligible studies, identified via PubMed (7 May 2026), were observational cohorts reporting multivariable\u2010adjusted hazard ratios (HRs) for TAC\/SARIFA positivity vs negativity, with cancer\u2010specific survival (CSS) and overall survival (OS) as endpoints. All included studies were retrospective in design. Study quality was assessed using the Newcastle\u2013Ottawa Scale (NOS). Adjusted HRs were pooled using random\u2010effects meta\u2010analysis with restricted maximum\u2010likelihood estimation and Hartung\u2013Knapp confidence intervals. Of 17 records identified, 12 CRC\u2010focused original publications were included in the qualitative synthesis. Seven cohorts (5,932 patients) contributed CSS and five cohorts (4,545 patients) OS data, drawn from eight independent cohorts across six studies. All studies were rated good quality (NOS 7\u20139\/9). TAC\/SARIFA positivity was associated with inferior CSS (pooled HR 1.77, 95% confidence interval [CI] 1.55\u20132.01) and OS (pooled HR 1.53, 95% CI 1.39\u20131.68), with no relevant heterogeneity detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TAC\/SARIFA positivity is independently associated with inferior CSS and OS in CRC, warranting prospective validation. We propose TAC as a more descriptive terminology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70237","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:20:38Z","timestamp":1784200838000},"page":"835-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Direct tumour\u2013adipocyte contact \/ Stroma\n                    <scp>AReactive<\/scp>\n                    Invasion Front Area (\n                    <scp>TAC<\/scp>\n                    \/\n                    <scp>SARIFA<\/scp>\n                    ) predicts adverse outcome in colorectal cancer: a focused evidence synthesis and meta\u2010analysis"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-3158","authenticated-orcid":false,"given":"Nic G","family":"Reitsam","sequence":"first","affiliation":[{"name":"Pathology, Faculty of Medicine University of Augsburg  Augsburg Germany"},{"name":"Bavarian Cancer Research Center (BZKF)  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-850X","authenticated-orcid":false,"given":"Bruno","family":"M\u00e4rkl","sequence":"additional","affiliation":[{"name":"Pathology, Faculty of Medicine University of Augsburg  Augsburg Germany"},{"name":"Bavarian Cancer Research Center (BZKF)  Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-4127","authenticated-orcid":false,"given":"Iris D","family":"Nagtegaal","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-5791","authenticated-orcid":false,"given":"Magali","family":"Svrcek","sequence":"additional","affiliation":[{"name":"Department of Pathology L\u00e9on B\u00e9rard Comprehensive Cancer Center  Lyon France"},{"name":"Sorbonne Universit\u00e9, LIMICS, INSERM UMRS 1142  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2014.00029"},{"key":"e_1_2_12_3_1","first-page":"14","article-title":"Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment","volume":"14","author":"Li N","year":"2023","journal-title":"Nat. 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