The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study

Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been describe...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Annals of surgical oncology 2023-06, Vol.30 (6), p.3320-3328
Hauptverfasser: El Asmar, Antoine, Demetter, Pieter, Fares, Fahd, Sclafani, Francesco, Hendlisz, Alain, Donckier, Vincent, Vermeulen, Peter, Liberale, Gabriel
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 3328
container_issue 6
container_start_page 3320
container_title Annals of surgical oncology
container_volume 30
creator El Asmar, Antoine
Demetter, Pieter
Fares, Fahd
Sclafani, Francesco
Hendlisz, Alain
Donckier, Vincent
Vermeulen, Peter
Liberale, Gabriel
description Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. Methods This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method. Results Two distinct HGP were identified: a pushing -type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating -type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (>50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP 60% had better OS (131 months) than those with P-HGP
doi_str_mv 10.1245/s10434-023-13118-x
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10175429</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2812280258</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-f75efb18655bbead65fdc584f0dbaf88a9aada4fa340bc44a74e829bb567a3903</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhS0EoqXwB1ggS2zYBPxMHDaoGqCtVMRIFLaW41zPuMrYU9uB9t_jMn1QFkiWfO3z3ePHQeglJW8pE_JdpkRw0RDGG8opVc3lI7RPZd0SraKPa01a1fSslXvoWc7nhNCOE_kU7fG2k6IXbB9tz9aAlymuQszFW_zDTDPg6PBHX9fBFnxcizjFlbdmwkcp_iprvDSlQAr5GlxUMYEtVV1C8iUGqOUXKCbXAfk9PsRLP8WCv5V5vHqOnjgzZXhxMx-g758_nS2Om9OvRyeLw9PGik6WxnUS3EBVK-UwgBlb6UYrlXBkHIxTyvTGjEY4wwUZrBCmE6BYPwyy7QzvCT9AH3a-23nYwGghlGQmvU1-Y9KVjsbrh0rwa72KPzWtvyQF66vDmxuHFC9myEVvfLYwTSZAnLNmXSdUL1spKvr6H_Q8zinU92mmKGOKMKkqxXaUTTHnBO7uNpTo60T1LlFdE9V_EtWXtenV3--4a7mNsAJ8B-QqhRWk-7P_Y_sbPECvaw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2812280258</pqid></control><display><type>article</type><title>The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>El Asmar, Antoine ; Demetter, Pieter ; Fares, Fahd ; Sclafani, Francesco ; Hendlisz, Alain ; Donckier, Vincent ; Vermeulen, Peter ; Liberale, Gabriel</creator><creatorcontrib>El Asmar, Antoine ; Demetter, Pieter ; Fares, Fahd ; Sclafani, Francesco ; Hendlisz, Alain ; Donckier, Vincent ; Vermeulen, Peter ; Liberale, Gabriel</creatorcontrib><description>Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. Methods This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method. Results Two distinct HGP were identified: a pushing -type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating -type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (&gt;50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP &lt;50% (9 months; p = 0.029). Patients with a P-HGP dominance &gt;60% had better OS (131 months) than those with P-HGP &lt;60% (41 months; p = 0.044). Conclusions This is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-023-13118-x</identifier><identifier>PMID: 36754942</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Growth patterns ; Humans ; Liver ; Liver Neoplasms - drug therapy ; Liver Neoplasms - surgery ; Medical prognosis ; Medicine ; Medicine &amp; Public Health ; Metastases ; Metastasis ; Oncology ; Percutaneous Coronary Intervention ; Peritoneal Neoplasms - secondary ; Peritoneal Surface Malignancy ; Peritoneum ; Peritoneum - pathology ; Pilot Projects ; Prognosis ; Retrospective Studies ; Surgery ; Surgical Oncology ; Tumor cells ; Tumors</subject><ispartof>Annals of surgical oncology, 2023-06, Vol.30 (6), p.3320-3328</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-f75efb18655bbead65fdc584f0dbaf88a9aada4fa340bc44a74e829bb567a3903</citedby><cites>FETCH-LOGICAL-c475t-f75efb18655bbead65fdc584f0dbaf88a9aada4fa340bc44a74e829bb567a3903</cites><orcidid>0000-0002-6635-4616</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-023-13118-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-023-13118-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36754942$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El Asmar, Antoine</creatorcontrib><creatorcontrib>Demetter, Pieter</creatorcontrib><creatorcontrib>Fares, Fahd</creatorcontrib><creatorcontrib>Sclafani, Francesco</creatorcontrib><creatorcontrib>Hendlisz, Alain</creatorcontrib><creatorcontrib>Donckier, Vincent</creatorcontrib><creatorcontrib>Vermeulen, Peter</creatorcontrib><creatorcontrib>Liberale, Gabriel</creatorcontrib><title>The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. Methods This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method. Results Two distinct HGP were identified: a pushing -type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating -type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (&gt;50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP &lt;50% (9 months; p = 0.029). Patients with a P-HGP dominance &gt;60% had better OS (131 months) than those with P-HGP &lt;60% (41 months; p = 0.044). Conclusions This is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker.</description><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Growth patterns</subject><subject>Humans</subject><subject>Liver</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - surgery</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Oncology</subject><subject>Percutaneous Coronary Intervention</subject><subject>Peritoneal Neoplasms - secondary</subject><subject>Peritoneal Surface Malignancy</subject><subject>Peritoneum</subject><subject>Peritoneum - pathology</subject><subject>Pilot Projects</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtv1DAUhS0EoqXwB1ggS2zYBPxMHDaoGqCtVMRIFLaW41zPuMrYU9uB9t_jMn1QFkiWfO3z3ePHQeglJW8pE_JdpkRw0RDGG8opVc3lI7RPZd0SraKPa01a1fSslXvoWc7nhNCOE_kU7fG2k6IXbB9tz9aAlymuQszFW_zDTDPg6PBHX9fBFnxcizjFlbdmwkcp_iprvDSlQAr5GlxUMYEtVV1C8iUGqOUXKCbXAfk9PsRLP8WCv5V5vHqOnjgzZXhxMx-g758_nS2Om9OvRyeLw9PGik6WxnUS3EBVK-UwgBlb6UYrlXBkHIxTyvTGjEY4wwUZrBCmE6BYPwyy7QzvCT9AH3a-23nYwGghlGQmvU1-Y9KVjsbrh0rwa72KPzWtvyQF66vDmxuHFC9myEVvfLYwTSZAnLNmXSdUL1spKvr6H_Q8zinU92mmKGOKMKkqxXaUTTHnBO7uNpTo60T1LlFdE9V_EtWXtenV3--4a7mNsAJ8B-QqhRWk-7P_Y_sbPECvaw</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>El Asmar, Antoine</creator><creator>Demetter, Pieter</creator><creator>Fares, Fahd</creator><creator>Sclafani, Francesco</creator><creator>Hendlisz, Alain</creator><creator>Donckier, Vincent</creator><creator>Vermeulen, Peter</creator><creator>Liberale, Gabriel</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6635-4616</orcidid></search><sort><creationdate>20230601</creationdate><title>The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study</title><author>El Asmar, Antoine ; Demetter, Pieter ; Fares, Fahd ; Sclafani, Francesco ; Hendlisz, Alain ; Donckier, Vincent ; Vermeulen, Peter ; Liberale, Gabriel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-f75efb18655bbead65fdc584f0dbaf88a9aada4fa340bc44a74e829bb567a3903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Growth patterns</topic><topic>Humans</topic><topic>Liver</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - surgery</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Oncology</topic><topic>Percutaneous Coronary Intervention</topic><topic>Peritoneal Neoplasms - secondary</topic><topic>Peritoneal Surface Malignancy</topic><topic>Peritoneum</topic><topic>Peritoneum - pathology</topic><topic>Pilot Projects</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Asmar, Antoine</creatorcontrib><creatorcontrib>Demetter, Pieter</creatorcontrib><creatorcontrib>Fares, Fahd</creatorcontrib><creatorcontrib>Sclafani, Francesco</creatorcontrib><creatorcontrib>Hendlisz, Alain</creatorcontrib><creatorcontrib>Donckier, Vincent</creatorcontrib><creatorcontrib>Vermeulen, Peter</creatorcontrib><creatorcontrib>Liberale, Gabriel</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Asmar, Antoine</au><au>Demetter, Pieter</au><au>Fares, Fahd</au><au>Sclafani, Francesco</au><au>Hendlisz, Alain</au><au>Donckier, Vincent</au><au>Vermeulen, Peter</au><au>Liberale, Gabriel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>30</volume><issue>6</issue><spage>3320</spage><epage>3328</epage><pages>3320-3328</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract>Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. Methods This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method. Results Two distinct HGP were identified: a pushing -type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating -type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (&gt;50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP &lt;50% (9 months; p = 0.029). Patients with a P-HGP dominance &gt;60% had better OS (131 months) than those with P-HGP &lt;60% (41 months; p = 0.044). Conclusions This is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>36754942</pmid><doi>10.1245/s10434-023-13118-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6635-4616</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1068-9265
ispartof Annals of surgical oncology, 2023-06, Vol.30 (6), p.3320-3328
issn 1068-9265
1534-4681
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10175429
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Chemotherapy
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - pathology
Growth patterns
Humans
Liver
Liver Neoplasms - drug therapy
Liver Neoplasms - surgery
Medical prognosis
Medicine
Medicine & Public Health
Metastases
Metastasis
Oncology
Percutaneous Coronary Intervention
Peritoneal Neoplasms - secondary
Peritoneal Surface Malignancy
Peritoneum
Peritoneum - pathology
Pilot Projects
Prognosis
Retrospective Studies
Surgery
Surgical Oncology
Tumor cells
Tumors
title The Prognostic Value of Distinct Histological Growth Patterns of Colorectal Peritoneal Metastases: A Pilot Study
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T16%3A45%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Prognostic%20Value%20of%20Distinct%20Histological%20Growth%20Patterns%20of%20Colorectal%20Peritoneal%20Metastases:%20A%20Pilot%20Study&rft.jtitle=Annals%20of%20surgical%20oncology&rft.au=El%20Asmar,%20Antoine&rft.date=2023-06-01&rft.volume=30&rft.issue=6&rft.spage=3320&rft.epage=3328&rft.pages=3320-3328&rft.issn=1068-9265&rft.eissn=1534-4681&rft_id=info:doi/10.1245/s10434-023-13118-x&rft_dat=%3Cproquest_pubme%3E2812280258%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2812280258&rft_id=info:pmid/36754942&rfr_iscdi=true