{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:00:05Z","timestamp":1792144805828,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal\/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with \u2018skip lesions\u2019 in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.<\/jats:p>","DOI":"10.3390\/medicina59101807","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:11:01Z","timestamp":1696990261000},"page":"1807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection"],"prefix":"10.3390","volume":"59","author":[{"given":"Haidy","family":"Elazzamy","sequence":"first","affiliation":[{"name":"Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Mazzara","sequence":"additional","affiliation":[{"name":"Pathology Department, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Barawi","sequence":"additional","affiliation":[{"name":"Gastroenterology, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer","family":"Zeni","sequence":"additional","affiliation":[{"name":"Rectal Surgery, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Aref","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Ascension St. John Hospital, Detroit, MI 48236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref_1","unstructured":"National Comprehensive Cancer Network (NCCN) (2017). NCCN Clinical Practice Guidelines in Oncology, Rectal Cancer, Version 3, NCCN. Available online: www.nccn.org."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00384-016-2659-6","article-title":"Long-term functional follow-up after anterior rectal resection for cancer","volume":"32","author":"Sturiale","year":"2017","journal-title":"Int. J. Color. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.clcc.2014.12.007","article-title":"Bowel function 14 years after preoperative short-course radiotherapy and total mesorectal excision for rectal cancer: Report of a multicenter randomized trial","volume":"14","author":"Chen","year":"2015","journal-title":"Clin. Color. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/DCR.0000000000001228","article-title":"Low anterior resection syndrome and quality of life after sphincter-sparing rectal cancer surgery: A long-term longitudinal follow-up","volume":"62","author":"Pieniowski","year":"2019","journal-title":"Dis. Colon Rectum"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1097\/DCR.0000000000001601","article-title":"Patient-reported work ability during the first two years after rectal cancer diagnosis","volume":"63","author":"Couwenberg","year":"2020","journal-title":"Dis. Colon Rectum"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/01.sla.0000141194.27992.32","article-title":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results","volume":"240","author":"Perez","year":"2004","journal-title":"Ann Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0140-6736(17)31056-5","article-title":"Organ preservation for rectal cancer (GRECCAR2): A prospective, randomised, open-label, multicentre, phase 3 trial","volume":"390","author":"Rullier","year":"2017","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.ejso.2017.05.011","article-title":"Transanal endoscopic microsurgery after neoadjuvant radiochemotherapy for locally advanced extraperitoneal rectal cancer","volume":"43","author":"Rizzo","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9556","DOI":"10.3748\/wjg.v20.i28.9556","article-title":"Treatment of rectal cancer by transanal endoscopic microsurgery: Experience with 425 patients","volume":"20","author":"Guerrieri","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1097\/DCR.0000000000000221","article-title":"Long-term outcome of local excision afer preoperative chemoradiation for ypT0 rectal cancer","volume":"57","author":"Stipa","year":"2014","journal-title":"Dis. Colon Rectum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1097\/DCR.0b013e3182a2303e","article-title":"Local excision after preoperative chemoradiotherapy for rectal cancer: Results of a multicenter phase II clinical trial","volume":"56","author":"Pucciarelli","year":"2013","journal-title":"Dis. Colon Rectum"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/DCR.0b013e3182083b84","article-title":"Transanal endoscopic microsurgery for residual rectal cancer after neoadjuvant chemoradiation therapy is associated with significant immediate pain and hospital readmission rates","volume":"54","author":"Perez","year":"2011","journal-title":"Dis. Colon Rectum"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1245\/s10434-011-1933-7","article-title":"A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: Preliminary results of the ACOSOG Z6041 trial","volume":"19","author":"Shi","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/DCR.0000000000000543","article-title":"Impact of organ-preserving strategies on anorectal function in patients with distal rectal cancer following neoadjuvant chemoradiation","volume":"59","author":"Lynn","year":"2016","journal-title":"Dis. Colon Rectum"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1055\/s-0041-1742112","article-title":"Transanal local excision of rectal cancer after neoadjuvant chemoradiation: Is there a place for it or should it be avoided at all costs?","volume":"35","author":"Perez","year":"2022","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/DCR.0000000000002398","article-title":"Should local excision after neoadjuvant therapy be included in the national guidelines for the treatment of locally advanced rectal cancer?","volume":"65","author":"Aref","year":"2022","journal-title":"Dis. Colon Rectum"},{"key":"ref_17","first-page":"1299","article-title":"Favorable postoperative complication rate after neoadjuvant therapy and transanal full thickness local excision for rectal cancer","volume":"4","author":"Aref","year":"2021","journal-title":"World J. Surg. Surg. Res."},{"key":"ref_18","first-page":"1315","article-title":"Pattern of distribution of residual microscopic disease following neoadjuvant therapy for rectal cancer","volume":"4","author":"Zhifei","year":"2021","journal-title":"World J. Surg. Surg. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1365-2559.2005.02176.x","article-title":"Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer","volume":"47","author":"Ryan","year":"2005","journal-title":"Histopathology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF02303553","article-title":"Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma","volume":"1","author":"Meterissian","year":"1994","journal-title":"Ann. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/DCR.0b013e31827541e2","article-title":"Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer","volume":"56","author":"Duldulao","year":"2013","journal-title":"Dis. Colon Rectum"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/SLA.0b013e3182196e1f","article-title":"Optimal timing of surgery after chemoradiation for advanced rectal cancer: Preliminary results of a multicenter, nonrandomized phase II prospective trial","volume":"254","author":"Smith","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"34923","DOI":"10.1038\/srep34923","article-title":"Pathological assessment of rectal cancer after neoadjuvant chemoradiotherapy: Distribution of residual cancer cells and accuracy of biopsy","volume":"10","author":"Xiao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1200\/JCO.22.00032","article-title":"Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy","volume":"40","author":"Patil","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_25","unstructured":"Gorgun, E. Personal Communication."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e717","DOI":"10.1097\/DCR.0000000000002244","article-title":"Endoscopic submucosal dissection in the management of an adenoma within the area of rectal cancer after complete clinical response","volume":"64","author":"Tatar","year":"2021","journal-title":"Dis. Colon Rectum"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.gie.2022.02.014","article-title":"Technical feasibility of salvage endoscopic submucosal dissection after chemoradiation for locally advanced rectal carcinoma","volume":"96","author":"Leung","year":"2022","journal-title":"Gastrointest. Endosc."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:39Z","timestamp":1760130279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/10\/1807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["medicina59101807"],"URL":"https:\/\/doi.org\/10.3390\/medicina59101807","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]}}}