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Hu X, Xie S, Yang Z, Zhao X, Gong L, Yang P, Yang L, Wang S, Bao G, He X. Aggressive characteristics of tumor deposits in colorectal cancer highlight the need for staging refinement in patients with 0-3 metastatic lymph nodes. Int J Cancer 2025; 156:1826-1839. [PMID: 39834167 DOI: 10.1002/ijc.35306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 12/01/2024] [Accepted: 12/04/2024] [Indexed: 01/22/2025]
Abstract
Accurate staging is essential for the optimal management of patients with colorectal cancer (CRC). The role of tumor deposits (TDs) in CRC staging has been contentious due to a lack of comprehensive understanding of their clinical and biological traits. In this retrospective study, we analyzed large data from 5718 CRC patients diagnosed between 2011 and 2022, ensuring rigorous data collection and long-term follow-up. Patients with positive TDs displayed aggressive clinical features. The risk factors for TDs varied among patients with different backgrounds of lymph node (LN) involvement, and the numbers of TDs and metastatic LNs showed a significantly positive correlation. TDs significantly impacted CRC prognosis, resulting in unfavorable outcomes irrespective of LN status. To delve into the biological characteristics of TDs, we performed transcriptome sequencing, immunohistochemistry, and Kaplan-Meier analyses on tissue samples from the additional CRC cohort and The Cancer Genome Atlas datasets. TDs exhibited aggressive biological phenotypes that were distinct from primary tumors and metastatic LNs, characterized by elevated signatures of epithelial-mesenchymal transition, angiogenesis, and immune suppression. Cox proportional hazards analysis was then applied to reassess the appropriate role of TDs within the TNM staging system, revealing that the prognostic weightiness of TDs in CRC corresponded to N2a rather than N1 in patients with 0-3 LN metastases. Overall, our comprehensive analysis showed that TDs, with their aggressive clinical and biological characteristics, could optimize the staging of CRC, highlighting the need to refine their role within the TNM staging system.
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Affiliation(s)
- Xi'e Hu
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Shuang Xie
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
- Department of General Surgery, 988 Hospital, Joint Logistics Support Force, Zhengzhou, Henan, China
| | - Zhenyu Yang
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Xin Zhao
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Li Gong
- Department of Pathology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Ping Yang
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Lin Yang
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Shoujia Wang
- Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi'an, Shaanxi, China
| | - Guoqiang Bao
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
| | - Xianli He
- Department of General Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shannxi, China
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Naves AA, Gouvea GDL, Machado CVB, Colli LM, Chahud F, Reis RB, Muglia VF. MRI-detected extranodal extension as a marker of prostate cancer aggressiveness. Eur Radiol 2025:10.1007/s00330-025-11532-1. [PMID: 40185926 DOI: 10.1007/s00330-025-11532-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 01/01/2025] [Accepted: 02/07/2025] [Indexed: 04/07/2025]
Abstract
OBJECTIVE Extranodal extension (ENE) is a histological marker of aggressiveness for various cancers. We evaluated if clinical ENE, detected by Magnetic Resonance Imaging, can also serve as a biological marker of Prostate Cancer (PCa) aggressiveness. MATERIALS AND METHODS This retrospective, single-center study analyzed patients diagnosed with PCa and had MRI on a 3-T scanner from January 2013 to December 2017. After exclusions, 461 patients were included and divided into: Group 1, no lymph node involvement (LNI), Group 2 (LNI without ENE), and Group 3 (LNI and ENE). Two experienced radiologists assessed the MRI scans for primary lesion characteristics, LNI and ENE. Reproducibility assessment was calculated for ENE and PI-RADS. Clinical outcomes, including Overall Survival (OS), Specific Survival Rate (SSR), and Progression-Free Survival (PFS), were analyzed. RESULTS Group 1 included 410 patients, Group 2, 32 patients, and Group 3, 19 patients. The prevalence of ENE was 4.1%. Significant differences between groups were observed for age, PSA, dPSA, ISUP scores, clinical risk stratification, and staging (all p < 0.01). The Kappa coefficient for ENE was 0.75 (95% CI: 0.56-0.90), and 0.48 (0.14-1.0) for PI-RADS. Cox proportional hazards model showed PSA (HR: 1.009; 95% CI = 1.003-1.015, p < 0.01) and ENE (HR: 8.50; 1.76-40.98, p < 0.01) were associated with SSR, and both ENE (HR: 8.18; 2.34-28.58, p < 0.01) and LNI (HR: 5.99, 1.97-18.17, p < 0.01) were linked to poor PFS. CONCLUSION MRI-detected ENE, despite low prevalence, is a predictor of SSR and PFS in PCa. These findings support ENE as an independent prognostic marker. Further prospective, multi-institutional studies are required to validate these results. KEY POINTS Question Pathological extranodal extension (pENE) has been described as a marker of worrisome prognosis in prostate cancer (PCa), but clinical ENE has not been evaluated as a marker of prognosis in PCa. Findings MRI-detected clinical ENE, had a low prevalence in our cohort (4.1%), but it was a predictor of specific survival rate and progression-free survival. Clinical relevance MRI-detected clinical ENE, a reproducible imaging feature, may serve as a non-invasive biomarker for aggressive prostate cancer. It correlates with poorer progression-free survival and specific survival rates, offering valuable prognostic insights for patient management.
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Affiliation(s)
- Aline Araújo Naves
- Department of Imaging, Oncology and Hematology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Gabriel de Lion Gouvea
- Department of Imaging, Oncology and Hematology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Camila V B Machado
- Department of Imaging, Oncology and Hematology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Leandro Machado Colli
- Department of Imaging, Oncology and Hematology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Fernando Chahud
- Department of Pathology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Rodolfo B Reis
- Department of Surgery and Anatomy, Urology Division, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
| | - Valdair F Muglia
- Department of Imaging, Oncology and Hematology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
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Saikeaw T, Tipmanee P, Chareonpornwattana P, Watthanasathitarpha G, Dasom K, Limvorapitak T. The prognostic outcome of tumor deposit in colorectal cancer beyond stage N staging. Surg Oncol 2025; 59:102203. [PMID: 40086296 DOI: 10.1016/j.suronc.2025.102203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 02/05/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Tumor deposits (TD) have been shown to have prognostic implications in patients diagnosed with colorectal cancer (CRC), although their impact appears to be modest compared to regional lymph node metastases. PATIENTS AND METHODS A retrospective analysis was conducted involving patients with colorectal cancer in stages I-III who underwent curative resections between January 2015 and December 2019 in the tertiary care center in Thailand. These patients were divided into two cohorts: TD positive and TD negative. Additionally, the patients were subsequently classified into N0, N1, and N2 groups. Disease-free survival and overall survival were compared. RESULTS Among the 1015 eligible patients, 176 (17.3 %) had tumor deposits (TD), while 374 patients (36.8 %) had positive lymph nodes (LN). The TD positive group demonstrated a significantly lower 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) compared to the TD negative group (73.5 % vs 85.9 %, p < 0.001 and 72.5 % vs 87.9 %, p < 0.001 respectively). Upon stratification by various N stages, the presence of TD was notably associated with DFS in the N1 group (5-year DFS: 84.3 % vs. 89.2 %, p = 0.006). Multivariate logistic analyses shown TD as an independent predictor of disease recurrence [p = 0.02; hazard ratio (HR):1.71 (1.11-2.64)]. CONCLUSION The presence of TD was significantly correlated with reduced overall survival (OS) and disease-free survival (DFS) in colorectal cancer, especially in patients with nodal metastases.
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Affiliation(s)
- Tanasit Saikeaw
- Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Phadungkiat Tipmanee
- Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pasut Chareonpornwattana
- Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | | | - Kanyanat Dasom
- Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thitithep Limvorapitak
- Colorectal Division, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Ji Y, Liu S, Zhang Y, Min Y, Wei L, Guan C, Yu H, Zhang Z. Lysine crotonylation in disease: mechanisms, biological functions and therapeutic targets. Epigenetics Chromatin 2025; 18:13. [PMID: 40119392 PMCID: PMC11929287 DOI: 10.1186/s13072-025-00577-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/24/2025] [Indexed: 03/24/2025] Open
Abstract
Lysine crotonylation (Kcr), a previously unknown post-translational modification (PTM), plays crucial roles in regulating cellular processes, including gene expression, chromatin remodeling, and cellular metabolism. Kcr is associated with various diseases, including neurodegenerative disorders, cancer, cardiovascular conditions, and metabolic syndromes. Despite advances in identifying crotonylation sites and their regulatory enzymes, the molecular mechanisms by which Kcr influences disease progression remain poorly understood. Understanding the interplay between Kcr and other acylation modifications may reveal opportunities for developing targeted therapies. This review synthesizes current research on Kcr, focusing on its regulatory mechanisms and disease associations, and highlights insights into future exploration in epigenetics and therapeutic interventions.
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Affiliation(s)
- Yu Ji
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Shanshan Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Yiqiao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Yiyang Min
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Luyang Wei
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Chengjian Guan
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
| | - Huajing Yu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University & State Key Lab of Digestive Health & National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
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Heng Y, Huang M, Xu J, Wu X, Huang N, Cao Y, Qin L. Prognostic value of tumor deposits and positive lymph nodes in colorectal cancer surgery: improved staging for long-term prognosis. BMC Gastroenterol 2025; 25:154. [PMID: 40069628 PMCID: PMC11899793 DOI: 10.1186/s12876-025-03713-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND To evaluate the prognostic value of the presence and number of tumor deposits (TDs) and the combination of TDs and number of positive lymph nodes (PLNs) in patients undergoing colorectal cancer (CRC) surgery, and to modify N staging. METHOD The clinical data of 1470 patients with stage I-IV CRC who underwent surgery in Wuhan Union Hospital from February 2014 to May 2018 were collected. The optimal cutoff value for TD + PLNs was obtained using X-tile software, and patients were regrouped accordingly. Cox univariate and multivariate analysis were used to screen the factors affecting the prognosis of patients. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive ability of independent prognostic factors for overall survival (OS) and disease-free survival (DFS) of patients. RESULT The presence of TD was associated with poor OS (HR = 2.478, 95%CI: 1.794-3.422, P<0.001) and DFS (HR = 2.516, 95%Cl: 1.874-3.377, P<0.001). Combined with TD and PLNs, a total of 128 of 395 N1 patients were reclassified re-staged as N2(TD + PLNs ≥ 3), which had a worse prognosis than those diagnosed with N1. Compared with Tumor Node Metastasis stage and TD number, the multivariate model constructed using independent prognostic factors showed better predictive power for OS (AUC:0.769 vs. 0.681 vs. 0.650) and DFS (AUC:0.757 vs. 0.702 vs. 0.650). CONCLUSION TD significantly affects the long-term prognosis of CRC patients. Combining TD and PLNs to redefine the tumor staging of CRC patients can improve the accuracy of long-term prognosis of surgical patients.
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Affiliation(s)
- Yixin Heng
- Department of General Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 832008, P. R. China
| | - Mudan Huang
- Department of Radiation Oncology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen, 5 18000, China
| | - Jiaxin Xu
- Department of General Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 832008, P. R. China
| | - Xiaoyu Wu
- Department of General Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 832008, P. R. China
| | - Ning Huang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Yinghao Cao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan, Hubei Province, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
| | - Le Qin
- Department of General Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 832008, P. R. China.
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Gong X, Ye Z, Shen Y, Song B. Enhancing the role of MRI in rectal cancer: advances from staging to prognosis prediction. Eur Radiol 2025:10.1007/s00330-025-11463-x. [PMID: 40045072 DOI: 10.1007/s00330-025-11463-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/19/2024] [Accepted: 01/28/2025] [Indexed: 03/17/2025]
Abstract
Rectal cancer (RC) is one of the major health challenges worldwide. Accurate staging, restaging, invasiveness assessment, and treatment efficacy evaluation are crucial for its clinical management. Magnetic resonance imaging (MRI) plays a significant role in these processes. However, standard MRI techniques, including T2-weighted and diffusion-weighted imaging, have uncertainties in identifying early-stage tumors, high-risk nodules, extramural vascular invasion, and treatment efficacy, potentially leading to inappropriate treatment. Recent advances suggest that the integration of traditional MRI methods, including diffusion-weighted imaging, opposed-phase or contrast-enhanced T1-weighted imaging, as well as emerging synthetic MRI, could address these challenges. Additionally, improvements in imaging technology have spurred research into advanced functional MRI techniques such as diffusion kurtosis imaging and amide proton transfer weighted MRI, yielding promising results in RC assessment. Total neoadjuvant therapy has emerged as a new treatment paradigm for locally advanced RC, with neoadjuvant immunotherapy and chemotherapy offering viable alternatives to neoadjuvant chemoradiotherapy. However, the lack of standards for the early prediction of patient survival and tumor response to neoadjuvant therapy highlights a critical unmet need in matching therapies to suitable patients. Furthermore, organ preservation strategies after neoadjuvant therapy provide personalized options based on tumor response and patient preferences, yet traditional MRI assessments show significant variability. Radiomics and artificial intelligence hold promise for revealing complex patterns in MRI images associated with patient prognosis and treatment response. This review provides an overview of current MRI advancements in RC assessment and emphasizes how future research can refine tailored treatment strategies to improve patient outcomes. KEY POINTS: Question The accurate diagnosis of early-stage rectal tumors, high-risk nodules, treatment responses, and the early prediction of patient survival and therapeutic outcomes remain an unmet need. Findings Visual MRI has improved staging, restaging, and invasiveness evaluation. Advanced MRI, radiomics and artificial intelligence provide significant potential for tumor characterization and outcome prediction. Clinical relevance Advances in visual MRI are improving routine imaging protocols and radiomics and artificial intelligence show promise in enhancing treatment decisions through precise tumor characterization and outcome prediction.
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Affiliation(s)
- Xiaoling Gong
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Ye
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Yu Shen
- Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
- Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
- Department of Radiology, Sanya People's Hospital, Sanya, China.
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Brouwer NPM, van Vliet S, IntHout J, De Wilt JHW, Simmer F, Hugen N, Nagtegaal ID. Tumour deposits are associated with worse survival than extranodal extension; a network meta-analysis on tumour nodules in colorectal cancer. Histopathology 2025; 86:485-496. [PMID: 39192780 PMCID: PMC11791726 DOI: 10.1111/his.15301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Lymph node metastases (LNM) play a central role in the tumour-node-metastasis (TNM) classification for colorectal cancer (CRC), with extranodal extension (ENE) as an adverse feature. ENE has never been directly compared to tumour deposits (TD). The aim of this study was to perform an up-to-date systematic review, including a network meta-analysis to compare their prognostic value. A comprehensive search was conducted on PubMed, Embase, Web of Science and Cochrane databases to identify all prognostic studies on ENE and TD. A total of 20 studies were included, with 7719 cases. The primary outcome was 5-year disease-free survival (DFS); secondary outcomes were overall survival (OS) and disease-specific survival (DSS). Frequentist paired and network meta-analyses were performed using the netmeta package in R. For univariable DFS analysis, LNM + TD+ cases had a significantly worse outcome compared with LNM + ENE+ cases [hazard ratio (HR) = 1.27, 95% confidence interval (CI) = 1.06-1.53], which was no longer significant for multivariable DFS analysis (HR = 1.13, 95% CI = 0.87-1.46). All OS and multivariable DSS analyses showed a significantly worse outcome for LNM + TD+ cases compared with LNM + ENE cases. For all outcomes, both LNM + TD+ and LNM + ENE+ had a significantly increased hazard compared with LNM+ cases. This study shows that there is a trend towards worse outcome for LNM + TD+ than LNM + ENE+, not statistically significant in multivariable DFS analysis. Both groups perform significantly worse than cases with LNM only. To improve the accuracy of CRC staging, we recommend to put more emphasis on both ENE and TD in the TNM classification, with the most prominent role for TD.
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Affiliation(s)
- Nelleke P M Brouwer
- Department of PathologyRadboud University Medical CenterNijmegenthe Netherlands
| | - Shannon van Vliet
- Department of PathologyRadboud University Medical CenterNijmegenthe Netherlands
| | - Joanna IntHout
- Department for Health EvidenceRadboud University Medical CenterNijmegenthe Netherlands
| | | | - Femke Simmer
- Department of PathologyRadboud University Medical CenterNijmegenthe Netherlands
| | - Niek Hugen
- Department of SurgeryNetherlands Cancer InstituteAmsterdamthe Netherlands
- Department of SurgeryRijnstate HospitalArnhemthe Netherlands
| | - Iris D Nagtegaal
- Department of PathologyRadboud University Medical CenterNijmegenthe Netherlands
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Oguz Erdogan AS, Brouwer NPM, Angerilli V, Rutgers N, Brown G, Simmer F, Nagtegaal ID. The number of potential gateways determines prognostic value of tumour deposits in colon cancer. Pathology 2025:S0031-3025(25)00088-1. [PMID: 40102143 DOI: 10.1016/j.pathol.2024.12.635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/25/2024] [Accepted: 12/06/2024] [Indexed: 03/20/2025]
Abstract
Tumour deposits (TD) are a crucial biomarker in colorectal cancer, closely associated with nearby structures such as blood vessels, lymphatic vessels, and peripheral nerves. These anatomical structures serve as pathways that facilitate the spread of tumour cells throughout the body. This study aims to investigate how TD access these anatomical gateways and how these variations impact patient survival. We analysed colon carcinoma patients who underwent surgery at Radboud University Medical Centre between 1986 and 2012 for the presence of TD. Using serial sections and immunohistochemistry with four different antibodies (CD34, D2-40, S100, and elastic van Gieson), we examined the presence and distribution of TD access to surrounding anatomical structures, including blood vessels, lymphatic vessels and peripheral nerves. In 127 patients, 280 TD were examined. Of these, 112 TD (40%) had multiple access points, 109 TD (39%) had a single access point, and 59 TD (21%) had no discernible access point. More than half of the TD (57%) demonstrated haematovascular invasion. Patients with TD featuring a single access point had a better prognosis compared to those with multiple access points (5-year overall survival, p=0.025; 5-year disease-free survival, p=0.005). TD are a heterogeneous biomarker characterised by various access points, with haematovascular invasion being the most common. Our study highlights a direct correlation between the number of TD access points and patient outcomes, indicating that an increase in access points is linked to a poorer prognosis.
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Affiliation(s)
| | - Nelleke P M Brouwer
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Valentina Angerilli
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Natasja Rutgers
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Gina Brown
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Femke Simmer
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
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van den Berg K, Banken E, van Rees JM, Coolen LM, de Vries M, Voogt ELK, Rothbarth J, Rutten HJT, Nederend J, van Hellemond IEG, Creemers GJM, Verhoef C, Burger JWA. Neoadjuvant chemotherapy and chemoradiotherapy versus chemoradiotherapy alone in high-risk locally advanced rectal cancer: A retrospective comparison of two Dutch tertiary referral centres. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109699. [PMID: 39987817 DOI: 10.1016/j.ejso.2025.109699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 01/02/2025] [Accepted: 02/12/2025] [Indexed: 02/25/2025]
Abstract
INTRODUCTION The effect of neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer, at increased risk of failing current treatment regimens, is unknown. This study compared the complete response rate and long-term survival of these patients treated with or without neoadjuvant chemotherapy prior to chemoradiotherapy. MATERIALS AND METHODS Patients with high-risk locally advanced rectal cancer, who were surgically treated or entered a watch and wait approach after neoadjuvant chemoradiotherapy with or without neoadjuvant chemotherapy in Erasmus Medical Centre or Catharina Hospital between 2016 and 2020, were retrospectively identified. High-risk was defined as the presence of tumour invasion into the mesorectal fascia, grade 4 extramural venous invasion, enlarged lateral lymph nodes, or tumour deposits. The primary endpoint was complete response rate, which was defined as a histopathological complete response or a sustained (during 12 months) clinical complete response. Long-term oncological outcomes were evaluated based on Kaplan-Meier and Cox regression survival analyses. RESULTS The neoadjuvant chemotherapy group consisted of 64 patients, of whom 61 (95.3 %) were treated with chemotherapy prior to chemoradiotherapy, the chemoradiotherapy group of 194 patients. The complete response rates were 25.0 % and 9.8 %, respectively (P = 0.002). The estimated 3-year overall survival was 92.2 % in the neoadjuvant chemotherapy group versus 66.9 % in the chemoradiotherapy group. CONCLUSION Excellent oncological outcomes were observed in patients with high-risk locally advanced rectal cancer selected during a multidisciplinary team (MDT) meeting for neoadjuvant chemotherapy and chemoradiotherapy. The actual difference with patients treated with chemoradiotherapy alone should be investigated in prospective trials. Pretreatment referral to expert MDTs is encouraged.
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Affiliation(s)
- K van den Berg
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands; Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
| | - E Banken
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands; Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J M van Rees
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - L M Coolen
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - M de Vries
- Department of Radiology, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - E L K Voogt
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - J Rothbarth
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - H J T Rutten
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands
| | - J Nederend
- Department of Radiology, Catharina Hospital, Eindhoven, the Netherlands
| | - I E G van Hellemond
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - G J M Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - C Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, University Hospital Rotterdam, the Netherlands
| | - J W A Burger
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
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Bhutiani N, Yousef MM, Yousef AM, Haque EU, Chang GJ, Konishi T, Bednarski BK, You YN, Shen JP, Uppal A. Does Extramural Vascular Invasion Predict Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer? Clin Colorectal Cancer 2025:S1533-0028(25)00018-0. [PMID: 40038019 DOI: 10.1016/j.clcc.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/31/2025] [Accepted: 02/03/2025] [Indexed: 03/06/2025]
Abstract
INTRODUCTION Extramural vascular invasion (EMVI) is associated with distant recurrence after treatment of locogionally advanced rectal adenocarcinomas (LARCs), but its use as a marker for response to neoadjuvant therapy is less well understood. We examined the relationship between EMVI and tumor or nodal category downstaging after treatment of LARCs with neoadjuvant therapy. METHODS Patients with EMVI categorized on initial staging pelvic MRI for LARC who underwent curative-intent surgery after neoadjuvant therapy at MD Anderson Cancer Center from 2016 to 2022 were identified. Patients received either preoperative chemoradiation or total neoadjuvant therapy (TNT). Associations between EMVI and demographic, radiologic, and clinicopathologic variables were analyzed. RESULTS EMVI was associated with higher rates of lymphovascular invasion (LVI) (46.2% vs. 27.8%, P = .001) and perineural invasion (PNI) (51.9% vs. 28.4%, P < .001) on final pathology. Patients with EMVI were more likely to have cT4 tumors (31.7% vs. 16.3%, P = .004) and cN+ status (86.8% vs. 66.3%, P = .001) and more likely to be treated with TNT rather than chemoradiation alone (62.3% vs. 41.9%, P = .005). EMVI was associated with a lower rate of pathologic complete or near-complete response (20.1% vs. 34.2%, P = .018), downstaging to ypT0-2 from cT3/4 tumors (14.9% vs. 44.4%, P = .0001), and downstaging to ypN0 from cN+ status (47.9% vs. 66.4%, P = .015). CONCLUSIONS Rectal tumors with EMVI are more likely to have higher clinical stage, less likely to respond to neoadjuvant therapy despite increased use of TNT, and more likely to have high-risk features for recurrence. This suggests EMVI is a marker of disease with poorer response to neoadjuvant therapy. Disease biology should be strongly considered in treatment decision-making, and new treatment strategies are needed to improve disease response.
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Affiliation(s)
- Neal Bhutiani
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY
| | - Mahmoud Mg Yousef
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Abdelrahman Mg Yousef
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Emaan U Haque
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - George J Chang
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Tsuyoshi Konishi
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brian K Bednarski
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Y Nancy You
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Abhineet Uppal
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Surgery, Division of Colon and Rectal Surgery, Emory University School of Medicine, Atlanta, GA.
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11
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Sun ZG, Chen SX, Sun BL, Zhang DK, Sun HL, Chen H, Hu YW, Zhang TY, Han ZH, Wu WX, Hou ZY, Yao L, Jie JZ. Important role of lymphovascular and perineural invasion in prognosis of colorectal cancer patients with N1c disease. World J Gastroenterol 2025; 31:102210. [PMID: 39926214 PMCID: PMC11718613 DOI: 10.3748/wjg.v31.i5.102210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/04/2024] [Accepted: 12/16/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with decreased survival in colorectal cancer (CRC), but its significance in N1c stage remains to be clearly defined. AIM To evaluate LVI and PNI as potential prognostic indicators in N1c CRC. METHODS We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital. Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients' outcomes. Disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method, with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using log-rank test. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic predictive ability. RESULTS The median follow-up time was 63.17 (45.33-81.37) months for DFS, with 33.64% (36/107) of patients experiencing recurrence; 21.5% of tumors were found to be LVI positive and 44.9% PNI positive. The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors (74.0% vs 35.6%), and PNI was similar (82.5% vs 45.1%). On multivariate analysis, LVI [hazard ratio (HR) = 3.368, 95% confidence interval (CI): 1.628-6.966, P = 0.001] and PNI (HR = 3.055, 95%CI: 1.478-6.313, P = 0.002) were independent prognostic factors for DFS. All patients could be divided into three groups of patients with different prognosis according to LVI and PNI. The 5-year ROC curve for LVI, PNI and their combination prediction of DFS was 0.646, 0.709 and 0.759, respectively. Similar results were seen for OS and CSS. CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients. Patients with LVI or PNI should be given more attention during treatment.
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Affiliation(s)
- Zhi-Gang Sun
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shao-Xuan Chen
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Bai-Long Sun
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Da-Kui Zhang
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hong-Liang Sun
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Huang Chen
- Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yu-Wan Hu
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
- Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Tong-Yin Zhang
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
- Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zi-Han Han
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Wen-Xiao Wu
- Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
| | - Zhi-Yong Hou
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Li Yao
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jian-Zheng Jie
- Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China
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12
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Sassun R, Sileo A, Ng JC, Violante T, Gomaa I, Mandrekar J, Rumer KK, McKenna NP, Larson DW. Validated Integration of Tumor Deposits in N Staging for Prognostication in Colon Cancer. JAMA Surg 2025:2829924. [PMID: 39908058 PMCID: PMC11800120 DOI: 10.1001/jamasurg.2024.6729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 11/07/2024] [Indexed: 02/06/2025]
Abstract
Importance Tumor deposits have prognostic value in colon cancer, but the current American Joint Committee on Cancer (AJCC) staging only considers them if there are no concurrent positive lymph nodes. Objective To devise a staging system for colon cancer by integrating counts of tumor deposits with positive lymph nodes while retaining the current AJCC staging framework. Design, Setting, and Participants This retrospective cohort study examines data from a large-volume, tertiary care center database (January 2010 through March 2023 with follow-up until December 2023) and the population-based National Cancer Database (January 2010 through December 2020 with follow-up until December 2021). Participants were adults (age 18-75 years) with stage III colon adenocarcinoma who underwent chemotherapy, and had a specified positive lymph node count and tumor deposit count were selected. Exposure A real positive lymph nodes count was developed and used to derive Sassun-Mayo N/tumor, lymph node, and metastasis (TNM) stages that were compared with the AJCC N/TNM stages. Main Outcomes and Measures Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses for 3-year overall survival were performed to assess the efficiency of the 2 staging systems. The concordance index was used for validation using the National Cancer Database. Results From a total patient number of 11 162 (institutional) and 848 704 (national), the final patient numbers were 788 and 77 790, respectively. The institutional database patients had a mean (SD) age of 58.5 (11.5) years; there were 433 male patients (54.9%) and 355 female (45.1%). The national database patients had a mean (SD) age of 59.3 (10.6) years; there were 40 315 male patients (51.8%) and 37 475 female (48.2%). ROC curve areas were improved using the Sassun-Mayo stages (3-year death for AJCC TMN, 0.63 [95% CI, 0.57-0.69] vs 0.66 [95% CI, for 0.60-0.72] for Sassun-Mayo TNM). Kaplan-Meier curves revealed visible overlaps among AJCC N stages, which were absent in the Sassun-Mayo N stages. The concordance index in the Sassun-Mayo N/TNM stages was 0.611 and 0.616, respectively, while in the AJCC N/TNM stages, it was 0.598 and 0.606, respectively. Patients upstaged from N1 to N2 (n = 10 307; 13.2%) had a 3-year overall survival rate nearly identical to that of AJCC N2a patients. Additionally, 3001 patients (3.9%) were upstaged from N2a to N2b, indicating that 13 308 patients (17.1%) with stage III colon cancer across cohorts were understaged. Conclusions and Relevance This study found that Sassun-Mayo N/TNM staging provided superior overall survival stratification compared with the current AJCC staging, suggesting that their implementation could improve prognostication in colon cancer.
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Affiliation(s)
- Richard Sassun
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Annaclara Sileo
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Jyi Cheng Ng
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Tommaso Violante
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Ibrahim Gomaa
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | - Jay Mandrekar
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Kristen K. Rumer
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
| | | | - David W. Larson
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota
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13
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Abbas A, Chu DI. Tumor Deposits-A Blind Spot in Colon Cancer Staging. JAMA Surg 2025:2829926. [PMID: 39908035 DOI: 10.1001/jamasurg.2024.6708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Affiliation(s)
- Alizeh Abbas
- Division of Gastrointestinal Surgery, Department of Surgery, University of Alabama at Birmingham
| | - Daniel I Chu
- Division of Gastrointestinal Surgery, Department of Surgery, University of Alabama at Birmingham
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14
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Rutegård MK, Båtsman M, Blomqvist L, Rutegård M, Axelsson J, Wu W, Ljuslinder I, Rutegård J, Palmqvist R, Brännström F, Riklund K. Evaluation of MRI characterisation of histopathologically matched lymph nodes and other mesorectal nodal structures in rectal cancer. Eur Radiol 2025:10.1007/s00330-025-11361-2. [PMID: 39838092 DOI: 10.1007/s00330-025-11361-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 11/17/2024] [Accepted: 12/11/2024] [Indexed: 01/23/2025]
Abstract
PURPOSE To evaluate current MRI-based criteria for malignancy in mesorectal nodal structures in rectal cancer. METHOD Mesorectal nodal structures identified on baseline MRI as lymph nodes were anatomically compared to their corresponding structures histopathologically, reported as lymph nodes, tumour deposits or extramural venous invasion. All anatomically matched nodal structures from patients with primary surgery and all malignant nodal structures from patients with neoadjuvant treatment were included. Mixed-effects logistic regression models were used to evaluate the morphological criteria irregular margin, round shape, heterogeneous signal and nodal size, as well as the combined 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria, with histopathological nodal status as the gold standard. RESULTS In total, 458 matched nodal structures were included from 46 patients (mean age, 67.7 years ± 1.5 [SD], 27 men), of which 19 received neoadjuvant treatment. The strongest associations in the univariable model were found for short-axis diameter ≥ 5 mm (OR 21.43; 95% CI: 4.13-111.29, p < 0.001) and heterogeneous signal (OR 9.02; 95% CI: 1.33-61.08, p = 0.024). Only size remained significant in multivariable analysis (OR 12.32; 95% CI: 2.03-74.57, p = 0.006). When applying the ESGAR consensus criteria to create a binary classification of nodal status, the OR of malignant outcome for nodes with positive ESGAR was 8.23 (95% CI: 2.15-31.50, p = 0.002), with corresponding sensitivity and specificity of 54% and 85%, respectively. CONCLUSION The results confirm the role of morphological and size criteria in predicting lymph node metastases. However, the current criteria might not be accurate enough for nodal staging. KEY POINTS Question Pretreatment lymph node staging in rectal cancer is challenging, and the ESGAR consensus criteria are not fully validated. Findings Although the ESGAR criteria correlated with malignant outcomes, diagnostic performance in terms of particular sensitivity, but also specificity, was not high. Clinical relevance Accurate nodal staging in rectal cancer is crucial for individual treatment planning. However, this validation of the current ESGAR consensus criteria suggests that these should be used with caution.
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Affiliation(s)
- Miriam Kheira Rutegård
- Department of Diagnostics and Intervention, Diagnostic Radiology, Umeå University, Umeå, Sweden.
| | - Malin Båtsman
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Lennart Blomqvist
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden
| | - Martin Rutegård
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Jan Axelsson
- Department of Diagnostics and Intervention, Radiation Physics, Umeå University, Umeå, Sweden
| | - Wendy Wu
- Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden
| | - Ingrid Ljuslinder
- Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden
| | - Jörgen Rutegård
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Richard Palmqvist
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Fredrik Brännström
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Katrine Riklund
- Department of Diagnostics and Intervention, Diagnostic Radiology, Umeå University, Umeå, Sweden
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15
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Liu X, Lin F, Li D, Lei N. The accuracy of radiomics in diagnosing tumor deposits and perineural invasion in rectal cancer: a systematic review and meta-analysis. Front Oncol 2025; 14:1425665. [PMID: 39845326 PMCID: PMC11750663 DOI: 10.3389/fonc.2024.1425665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 12/18/2024] [Indexed: 01/24/2025] Open
Abstract
Background Radiomics has emerged as a promising approach for diagnosing, treating, and evaluating the prognosis of various diseases in recent years. Some investigators have utilized radiomics to create preoperative diagnostic models for tumor deposits (TDs) and perineural invasion (PNI) in rectal cancer (RC). However, there is currently a lack of comprehensive, evidence-based support for the diagnostic performance of these models. Thus, the accuracy of radiomic models was assessed in diagnosing preoperative RC TDs and PNI in this study. Methods PubMed, EMBASE, Web of Science, and Cochrane Library were searched for relevant articles from their establishment up to December 11, 2023. The radiomics quality score (RQS) was used to evaluate the risk of bias in the methodological quality and research level of the included studies. Results This meta-analysis included 15 eligible studies, most of which employed logistic regression models (LRMs). For diagnosing TDs, the c-index, sensitivity, and specificity of models based on radiomic features (RFs) alone were 0.85 (95% CI: 0.79 - 0.90), 0.85 (95% CI: 0.75 - 0.91), and 0.82 (95% CI: 0.70 - 0.89); in the validation set, the c-index, sensitivity, and specificity of models based on both RFs and interpretable CFs were 0.87 (95% CI: 0.83 - 0.91), 0.91 (95% CI: 0.72 - 0.99), and 0.65 (95% CI: 0.53 - 0.76), respectively. For diagnosing PNI, the c-index, sensitivity, and specificity of models based on RFs alone were 0.80 (95% CI: 0.74 - 0.86), 0.64 (95% CI: 0.44 - 0.80), and 0.79 (95% CI: 0.68 - 0.87) in the validation set; in the validation set, the c-index, sensitivity, and specificity of models based on both RFs and interpretable CFs were 0.83 (95% CI: 0.77 - 0.89), 0.60 (95% CI: 0.48 - 0.71), and 0.90 (95% CI: 0.84 - 0.94), respectively. Conclusions Diagnostic models based on both RFs and CFs have proven effective in preoperatively diagnosing TDs and PNI in RC. This non-invasive method shows promise as a new approach. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=498660, identifier CRD42024498660.
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Affiliation(s)
| | | | | | - Nan Lei
- Radiology Department, The People’s Hospital of Lezhi,
Ziyang, Sichuan, China
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16
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Nougaret S, Gormly K, Lambregts DMJ, Reinhold C, Goh V, Korngold E, Denost Q, Brown G. MRI of the Rectum: A Decade into DISTANCE, Moving to DISTANCED. Radiology 2025; 314:e232838. [PMID: 39772798 DOI: 10.1148/radiol.232838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Over the past decade, advancements in rectal cancer research have reshaped treatment paradigms. Historically, treatment for locally advanced rectal cancer has focused on neoadjuvant long-course chemoradiotherapy, followed by total mesorectal excision. Interest in organ preservation strategies has been strengthened by the introduction of total neoadjuvant therapy with improved rates of complete clinical response. The administration of systemic induction chemotherapy and consolidation chemoradiotherapy in the neoadjuvant setting has introduced a new dimension to the treatment landscape and patients now face a more intricate decision-making process, given the expanded therapeutic options. This complexity underlines the importance of shared decision-making and brings to light the crucial role of radiologists. MRI, especially high-spatial-resolution T2-weighted imaging, is heralded as the reference standard for rectal cancer management because of its exceptional ability to provide staging and prognostic insights. A key evolution in MRI interpretation for rectal cancer is the transition from the DISTANCE mnemonic to the more encompassing DISTANCED-DIS, distal tumor boundary; T, T stage; A, anal sphincter complex; N, nodal status; C, circumferential resection margin; E, extramural venous invasion; D, tumor deposits. This nuanced shift in the mnemonic captures a wider range of diagnostic indicators. It also emphasizes the escalating role of radiologists in steering well-informed decisions in the realm of rectal cancer care.
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Affiliation(s)
- Stephanie Nougaret
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Kirsten Gormly
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Doenja M J Lambregts
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Caroline Reinhold
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Vicky Goh
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Elena Korngold
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Quentin Denost
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Gina Brown
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
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17
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Illarionova S, Hamoudi R, Zapevalina M, Fedin I, Alsahanova N, Bernstein A, Burnaev E, Alferova V, Khrameeva E, Shadrin D, Talaat I, Bouridane A, Sharaev M. A hierarchical algorithm with randomized learning for robust tissue segmentation and classification in digital pathology. Inf Sci (N Y) 2025; 686:121358. [DOI: 10.1016/j.ins.2024.121358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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18
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Feng FW, Jiang FY, Liu YQ, Sun Q, Hong R, Hu CH, Hu S. Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer. Eur Radiol 2025; 35:105-116. [PMID: 38987399 DOI: 10.1007/s00330-024-10918-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 04/24/2024] [Accepted: 05/25/2024] [Indexed: 07/12/2024]
Abstract
OBJECTIVE To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.
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Affiliation(s)
- Fei-Wen Feng
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fei-Yu Jiang
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuan-Qing Liu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Medical Imaging, Soochow University, Suzhou, China
| | - Qi Sun
- Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Rong Hong
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chun-Hong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
- Institute of Medical Imaging, Soochow University, Suzhou, China.
| | - Su Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
- Institute of Medical Imaging, Soochow University, Suzhou, China.
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19
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Lundström S, Agger E, Lydrup ML, Jörgren F, Buchwald P. Tumour deposit count is an independent prognostic factor in colorectal cancer-a population-based cohort study. Br J Surg 2024; 112:znae309. [PMID: 39787029 PMCID: PMC11683728 DOI: 10.1093/bjs/znae309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/12/2024] [Accepted: 11/30/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Tumour deposits are a prognostic factor for overall survival and distant metastasis in lymph node-negative colorectal cancer. However, the current TNM staging system does not account for the presence of tumour deposits in lymph node-positive colorectal cancer, or for the presence of multiple deposits. This study aimed to investigate the prognostic effect of tumour deposit count in patients with colorectal cancer. METHODS Patients who underwent curative surgery for colorectal cancer between 2016 and 2019 were identified nationwide from the Swedish Colorectal Cancer Registry. Patients with undisclosed tumour deposit status/count and stage IV disease were excluded. Univariable and multivariable Cox regression analyses were used to assess the prognostic effect of tumour deposit count on overall survival and distant metastasis adjusted for age, sex, neoadjuvant treatment, and number of positive lymph nodes. RESULTS Of 18 913 patients assessed, 14 154 patients were analysed with tumour deposits (TDs) present in 1702 (12%) patients. Patients were stratified by tumour deposit count (0, 1, 2, 3, 4, and ≥5 TDs). Increased tumour deposit count was associated with decreased 5-year overall survival (79%, 70%, 61%, 66%, 50%, 49%) and increased 5-year risk for distant metastasis (14%, 26%, 35%, 41%, 48%, 54%) respectively. Tumour deposit count remained an independent negative prognostic factor after multivariable Cox regression analysis. CONCLUSION Tumour deposit count is a negative prognostic predictor of both overall survival and distant metastasis in colorectal cancer, independent of positive lymph nodes or neoadjuvant treatment. These findings suggest that tumour deposit count should be integrated into the TNM staging regardless of lymph nodes status to improve prognostic accuracy.
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Affiliation(s)
- Simon Lundström
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Erik Agger
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Marie-Louise Lydrup
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Fredrik Jörgren
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Surgery, Helsingborg Hospital, Lund University, Helsingborg, Sweden
| | - Pamela Buchwald
- Department of Surgery, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
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20
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Chen RJ, Xu D, Fan XY, Qiao YH, Jiang XJ, Hao J, Du YT, Chen XH, Guo Y, Zhu J, Li JP. Assessing the clinical utility of tumor invasion proportion of lymph nodes for enhanced risk stratification in N1 colorectal cancer. Am J Cancer Res 2024; 14:5826-5838. [PMID: 39803664 PMCID: PMC11711517 DOI: 10.62347/dfxc4525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025] Open
Abstract
N staging systems are paramount clinical features for colorectal cancer (CRC). In N1 stage (N1) CRC, patients present with a limited number of metastatic lymph nodes, yet their prognoses vary widely. The tumor invasion proportion of lymph nodes (TIPLN) has gained attention, but its prognostic value in N1 CRC remains unclear. We retrospectively analyzed 416 N1 CRC patients who underwent radical surgery from January 2014 to December 2018, reviewing 713 hematoxylin and eosin (H&E)-stained slides to assess TIPLN. Overall survival was the primary outcome in our study. Using restricted cubic splines, we explored the relationship between TIPLN and prognosis, with Cox regression and subgroup analyses adjusting for potential confounders. We found that increased TIPLN was associated with an unfavorable prognosis. At a cut-off value of 50%, patients with high-TIPLN exhibiting poorer outcomes than their low-TIPLN counterparts (hazard ratio: 3.77, P < 0.001). Furthermore, high-TIPLN was confirmed as an independent risk factor for overall survival (hazard ratio: 3.12, P < 0.001) after adjusting for clinical confounders. Notably, TIPLN could also enhance risk stratification within the T and N stages, where patients with low-risk (T1-3 stage) and high-TIPLN demonstrated poorer overall survival compared to those with high-risk (T4 stage) and low-TIPLN (hazard ratio: 2.54, P = 0.021). In conclusion, TIPLN is a promising prognostic indicator for N1 CRC patients that complements traditional N staging system for a more comprehensive evaluation. Integrating TIPLN into the TNM staging system could enhance risk stratification and guide treatment decisions.
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Affiliation(s)
- Ru-Jie Chen
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Dong Xu
- Division of Digestive Surgery, Xi’an International Medical Center Hospital of Digestive DiseasesXi’an, Shaanxi, China
| | - Xiao-Yan Fan
- Department of Experiment Surgery, Xijing Hospital, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Yi-Huan Qiao
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Xun-Jiang Jiang
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Jun Hao
- Department of Experiment Surgery, Xijing Hospital, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Yong-Tao Du
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Xi-Hao Chen
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
| | - Yuan Guo
- Department of Breast, Shaanxi Provincial Cancer HospitalXi’an, Shaanxi, China
| | - Jun Zhu
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
- Department of General Surgery, The Southern Theater Air Force HospitalGuangzhou, Guangdong, China
| | - Ji-Peng Li
- Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical UniversityXi’an, Shaanxi, China
- Department of Experiment Surgery, Xijing Hospital, Fourth Military Medical UniversityXi’an, Shaanxi, China
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21
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Eltelety AM, Zaki A, Dewidar H, Anis SE, Batawi AE, Nassar AA. Malignant Soft Tissue Deposits in Advanced Cancer Larynx, a Prospective Study. Indian J Otolaryngol Head Neck Surg 2024; 76:5513-5520. [PMID: 39559116 PMCID: PMC11569053 DOI: 10.1007/s12070-024-05021-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/22/2024] [Indexed: 11/20/2024] Open
Abstract
The purpose of this study was to evaluate the incidence and predictors of malignant soft tissue deposits (MSTDs) in advanced laryngeal carcinoma. MSTDs prognostic value on locoregional recurrence within 2 years after curative surgery was also studied. 40 patients with cT3/cT4 N0 laryngeal squamous cell carcinoma (SCC) were prospectively involved in the study. Soft tissue specimens were histopathologically examined for MSTDs. MSTDs were observed in 4 patients. Six patients had extranodal extension (ENE), four of whom showed MSTDs. All patients with MSTDs had associated comorbidities. cTNM staging, preoperative tracheostomy, tumor grade and surgical margins were not related to the incidence of MSTDs. The incidence of MSTDs in our report was less than that previously reported in the literature. MSTDs did not influence locoregional recurrence and did not influence the overall outcome. MSTDs were less significant as a prognostic factor in comparison to other factors such as ENE.
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Affiliation(s)
- Ahmad Mohamed Eltelety
- Otolaryngology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
| | - Amir Zaki
- Otolaryngology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
| | - Hazem Dewidar
- Otolaryngology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
| | - Shady Elia Anis
- Pathology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
| | - Ahmed El Batawi
- Otolaryngology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
| | - Ahmed Amin Nassar
- Otolaryngology Department, Al Kasr Al Ainy School of Medicine, Cairo University, Giza, 11562 Egypt
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22
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Bhutiani N, Peacock O, Uppal A, Hu CY, Bednarski BK, Taggart MW, Dasari A, Morris VK, Kaur H, Kopetz S, Holliday EB, Das P, You YN, Chang GJ. The prognostic impact of tumor deposits in colorectal cancer: More than just N1c. Cancer 2024; 130:4052-4060. [PMID: 39306694 DOI: 10.1002/cncr.35491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/06/2024] [Accepted: 06/12/2024] [Indexed: 11/10/2024]
Abstract
BACKGROUND The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.
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Affiliation(s)
- Neal Bhutiani
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Oliver Peacock
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Abhineet Uppal
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Chung-Yuan Hu
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Brian K Bednarski
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Melissa W Taggart
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Van K Morris
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Harmeet Kaur
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Emma B Holliday
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Prajnan Das
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Y Nancy You
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - George J Chang
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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23
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Zhong Z, Cheng S, Liu Y. CKAP2 Regulated by TFDP1 Promotes Metastasis and Proliferation of Colorectal Cancer through Affecting the Tumor Microenvironment. J Microbiol Biotechnol 2024; 34:2211-2222. [PMID: 39403723 PMCID: PMC11637825 DOI: 10.4014/jmb.2407.07008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/20/2024] [Accepted: 09/06/2024] [Indexed: 11/29/2024]
Abstract
The current pathological and physiological evaluation system for colorectal cancer (CRC) is limited; thus, effective biological targets to diagnose and treat this disease are urgently needed. In this study, we used qRT-PCR for detecting mRNA levels of genes. The levels of protein were identified by western blot, immunohistochemistry, and immunofluorescence assays. In addition, functional experiments were used to evaluate the role of cytoskeleton associated protein (CKAP) 2 in CRC cells and human umbilical vein endothelial cells (HUVECs). Bioinformatics analysis was employed to predict the binding relationship of CKAP2 and TFDP1, which was confirmed through dual luciferase reporter assay and immunoprecipitation assay. Furthermore, we injected human colorectal carcinoma HCT116 cells into mice flanks, and we injected Luciferase-labeled HCT116 cells into mice tail vein. HE staining was used to detect tumor nodules. As a result, high CKAP2 expression was found in CRC cells and tissues. CKAP2 silencing reduced CRC cell migration, invasion, proliferation, and epithelial-mesenchymal transition. Moreover, CKAP2 expression was positively associated with M2 macrophage levels. CKAP2 promoted protein expression of CD86, CD206, IL-1β, and CCL17. Moreover, CKAP2 promoted the proliferation of HUVECs and angiogenesis via affecting the tumor microenvironment (TME). We also found that CKAP2 could interact with TFDP1. The inhibitory impacts of TFDP1 downregulation on CRC cell' proliferation, migration, and invasion were reversed via CKAP2 overexpression. In vivo silencing of CKAP2 repressed tumor growth and metastasis. Overall, CKAP2 was positively regulated by TFDP1, which promoted tumorigenesis and metastasis in CRC.
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Affiliation(s)
- Zhiqiang Zhong
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China
| | - Shi Cheng
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China
| | - Yang Liu
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China
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24
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Deng J, Qin JH, Li X, Tao D, Feng Y. Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens. Hum Cell 2024; 38:13. [PMID: 39495391 PMCID: PMC11534897 DOI: 10.1007/s13577-024-01139-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 09/13/2024] [Indexed: 11/05/2024]
Abstract
Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.
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Affiliation(s)
- Jiao Deng
- Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Jerry H Qin
- Wuhan Britain-China Senior High School, Wuhan, 430030, China
| | - Xiaolan Li
- Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Deding Tao
- Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yongdong Feng
- Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
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25
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Karaoğlan BB, Öztürk İ, Akyol C, Savaş B, Utkan G. Adjuvant Chemotherapy Duration and Disease-Free Survival in Low-Risk Stage III Colon Cancer with N1a-b and N1c Disease: Insights from a Single-Center Retrospective Analysis. J Gastrointest Cancer 2024; 56:14. [PMID: 39480587 DOI: 10.1007/s12029-024-01135-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND Tumor deposits (TDs) are known to have a poor prognosis independent of lymph node (LN) involvement and are considered equivalent to LN metastases in the latest staging system. In stage III colon cancer (CC), high-risk patients (pT4 or pN2) receive 6 months of adjuvant chemotherapy, while low-risk patients (pT1-3 and N1) are recommended either 3 or 6 months of CAPOX or 6 months of FOLFOX therapy. However, the optimal chemotherapy duration for low-risk patients classified as pN1c remains unknown. The aim of this study is to investigate the impact of adjuvant chemotherapy duration (3 months vs. 6 months) on survival in patients with low-risk stage III CC either in pN1a-b and pN1c patient groups. METHODS We retrospectively analyzed patients with stage III CC who underwent surgery at a tertiary center between January 2014 and May 2024. Demographic and pathological data of patients were retrospectively collected. The primary outcome was disease-free survival (DFS). RESULTS A total of 142 patients were included. Among the patients, 116 were pT1-3N1a-b and 26 were pT1-3N1c. Local (23.1% vs. 1.7%, P < 0.001) and overall (38.5% vs 14.6%, P = 0.011) recurrences were significantly higher in the pN1c group. Univariate and multivariate analyses revealed no significant impact of adjuvant chemotherapy duration on DFS in the pN1a-b group (P = 0.359), whereas in the pN1c group, 3-month chemotherapy resulted in significantly shorter DFS (P = 0.044) in univariate analysis. CONCLUSION Our study indicates that shorter duration of adjuvant chemotherapy is associated with worse survival and 6-month chemotherapy is recommended for patients with pT1-3 and N1c disease.
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Affiliation(s)
- Beliz Bahar Karaoğlan
- Faculty of Medicine, Department of Medical Oncology, Ankara University, Ankara, Türkiye.
| | - İremsu Öztürk
- Faculty of Medicine, Department of Medical Oncology, Ankara University, Ankara, Türkiye
| | - Cihangir Akyol
- Faculty of Medicine, Department of Surgery, Ankara University, Ankara, Türkiye
| | - Berna Savaş
- Faculty of Medicine, Department of Pathology, Ankara University, Ankara, Türkiye
| | - Güngör Utkan
- Faculty of Medicine, Department of Medical Oncology, Ankara University, Ankara, Türkiye
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26
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Brouwer NPM, Oguz Erdogan AS, van Vliet S, Rutgers N, Knijn N, van Lijnschoten G, Tan JJ, de Wilt JHW, Hugen N, Brown G, Simmer F, Nagtegaal ID. Unraveling the routes to distant metastases in colorectal cancer: Tumor deposits and lymph node metastases as the gateway. Cancer Commun (Lond) 2024; 44:1209-1213. [PMID: 39183541 DOI: 10.1002/cac2.12598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 06/25/2024] [Accepted: 07/13/2024] [Indexed: 08/27/2024] Open
Affiliation(s)
| | - Ayse Selcen Oguz Erdogan
- Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands
| | - Shannon van Vliet
- Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands
| | - Natasja Rutgers
- Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands
| | - Nikki Knijn
- Department of Pathology, PathologyDNA, Arnhem, Gelderland, The Netherlands
| | - Gesina van Lijnschoten
- Department of Pathology, Eurofins/Laboratoria voor Pathologie en Medische Microbiologie Nederland, Eindhoven, Noord-Brabant, The Netherlands
| | - Jessica Juliana Tan
- GI Cancer Imaging Research Unit, The Royal Marsden Hospital, Sutton, London, United Kingdom
| | | | - Niek Hugen
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands
- Department of Surgery, Rijnstate Hospital, Arnhem, Gelderland, The Netherlands
| | - Gina Brown
- Imperial College London Hammersmith Campus, London, London, United Kingdom
| | - Femke Simmer
- Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands
| | - Iris Dionne Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, The Netherlands
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Yu C, Shi Z, Zhou G, Chang X. Revisiting the survival paradox between stage IIB/C and IIIA colon cancer. Sci Rep 2024; 14:22133. [PMID: 39333782 PMCID: PMC11436827 DOI: 10.1038/s41598-024-73496-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Patients with stage IIB/C (T4a-bN0) colon cancer often exhibit worse survival rates compared to those with stage IIIA (T1-2N1, T1N2a) colon cancer. This study re-evaluates the survival paradox using the latest Surveillance, Epidemiology, and End Results (SEER) data (released on April 17, 2024) to inform potential revisions to the staging criteria. Utilizing SEER data with 8th edition TNM staging criteria, 4692 colon cancer patients diagnosed between 2018 and 2021 were analyzed with chi-square test. Cox regression and Kaplan-Meier survival analysis were employed to assess factors associated with cancer-specific survival (CSS) and overall survival (OS). The 3-year CSS rates for stage IIB and IIC were 73.1% and 70.3%, respectively, whereas stage IIIA had a substantially higher CSS rate of 91% (P < 0.001). Similarly, the OS rates were 64.9% and 63.0% for stage IIB and IIC, respectively, compared to 83.1% for stage IIIA (P < 0.001). Multivariate analyses revealed stage IIIA patients had significantly lower risks of cancer-specific mortality (hazard ratio (HR) = 0.374, 95% CI: 0.296-0.473, P < 0.001) and overall mortality (HR = 0.575, 95% CI: 0.483-0.685, P < 0.001) compared to stage IIB patients. The upcoming 9th edition of the AJCC staging system should address this paradox by integrating advanced diagnostic markers and emphasizing the aggressive biology of T4 tumor, providing more accurate prognostic information and guiding more effective treatment strategies for colon cancer patients.
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Affiliation(s)
- Cheng Yu
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Zhiliang Shi
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Guoqiang Zhou
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Xu Chang
- Department of General Surgery, Changshu No.5 People's Hospital, No. 289, Zhujiang Road, Changshu, 215500, Jiangsu, China.
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Ma T, Qin Z, Xu G, Zheng PW, Feng L, Ma D, Fu Z, Gao X. Negative prognostic impact of tumor deposits in stage III colorectal cancer patients. PLoS One 2024; 19:e0310327. [PMID: 39325798 PMCID: PMC11426431 DOI: 10.1371/journal.pone.0310327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/28/2024] [Indexed: 09/28/2024] Open
Abstract
BACKGROUND The prognostic value of tumor deposits (TDs) in stage III colorectal cancer (CRC) patients is poorly described based on the current tumor node metastasis (TNM) stage system. MATERIALS AND METHODS Based on the data from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 to 2020 and local hospital between 2006 to 2022, the clinicopathological features of stage III CRC patients with TDs were screened by Chi-square test. Kaplan-Meier curves were performed to describe the significant difference in overall survival (OS) among the different groups, and log-rank tests were used to compare the cumulative survival distributions. RESULT Patients with TDs exhibited more aggressive tumors, characterized by advanced T staging (T3&T4), N staging (N2), perineural invasion, and more advanced TNM stage. The presence of TDs was identified as a negative prognostic factor in stage III CRC patients, with the co-existence of TDs and lymph node metastasis associated the poorest prognosis. A pairwise comparison revealed no statistically significant difference between TD+N1a/b and N1c groups, while the OS of TD-LN+ (TD- N1a/b) patients was the most favorable within the N1 stage. Notably, patients with a single lymph node positive had a significantly better OS than those with a single TD positive. CONCLUSION The presence of tumor deposits was a negative prognostic factor in stage III colorectal cancer patients, and the significance of tumor deposits was underestimated in the current TNM staging system.
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Affiliation(s)
- Ting Ma
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang Province, China
| | - Zhaofu Qin
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Guohui Xu
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Peng-Wen Zheng
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Longhai Feng
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Dening Ma
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang Province, China
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Zhixuan Fu
- Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
| | - Xinyi Gao
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China
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Curcean S, Curcean A, Martin D, Fekete Z, Irimie A, Muntean AS, Caraiani C. The Role of Predictive and Prognostic MRI-Based Biomarkers in the Era of Total Neoadjuvant Treatment in Rectal Cancer. Cancers (Basel) 2024; 16:3111. [PMID: 39272969 PMCID: PMC11394290 DOI: 10.3390/cancers16173111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/02/2024] [Accepted: 09/06/2024] [Indexed: 09/15/2024] Open
Abstract
The role of magnetic resonance imaging (MRI) in rectal cancer management has significantly increased over the last decade, in line with more personalized treatment approaches. Total neoadjuvant treatment (TNT) plays a pivotal role in the shift from traditional surgical approach to non-surgical approaches such as 'watch-and-wait'. MRI plays a central role in this evolving landscape, providing essential morphological and functional data that support clinical decision-making. Key MRI-based biomarkers, including circumferential resection margin (CRM), extramural venous invasion (EMVI), tumour deposits, diffusion-weighted imaging (DWI), and MRI tumour regression grade (mrTRG), have proven valuable for staging, response assessment, and patient prognosis. Functional imaging techniques, such as dynamic contrast-enhanced MRI (DCE-MRI), alongside emerging biomarkers derived from radiomics and artificial intelligence (AI) have the potential to transform rectal cancer management offering data that enhance T and N staging, histopathological characterization, prediction of treatment response, recurrence detection, and identification of genomic features. This review outlines validated morphological and functional MRI-derived biomarkers with both prognostic and predictive significance, while also exploring the potential of radiomics and artificial intelligence in rectal cancer management. Furthermore, we discuss the role of rectal MRI in the 'watch-and-wait' approach, highlighting important practical aspects in selecting patients for non-surgical management.
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Affiliation(s)
- Sebastian Curcean
- Department of Radiation Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
- Department of Radiation Oncology, 'Prof. Dr. Ion Chiricuta' Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Andra Curcean
- Department of Imaging, Affidea Center, 15c Ciresilor Street, 400487 Cluj-Napoca, Romania
| | - Daniela Martin
- Department of Radiation Oncology, 'Prof. Dr. Ion Chiricuta' Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Zsolt Fekete
- Department of Radiation Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
- Department of Radiation Oncology, 'Prof. Dr. Ion Chiricuta' Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Alexandru Irimie
- Department of Oncological Surgery and Gynecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
- Department of Oncological Surgery, 'Prof. Dr. Ion Chiricuta' Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Alina-Simona Muntean
- Department of Radiation Oncology, 'Prof. Dr. Ion Chiricuta' Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Cosmin Caraiani
- Department of Medical Imaging and Nuclear Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
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Kim J, Lee DW, Park JW, Ryoo SB, Oh HK, Shin R, Choi JS, Kim MJ, Park SC, Kim DW, Heo SC, Kang SB, Jeong SY, Park KJ, Oh JH. Tumor Deposits as an Adverse Prognostic Indicator in Stage III Colon Cancer: A Multicenter Database Study. ANNALS OF SURGERY OPEN 2024; 5:e456. [PMID: 39310346 PMCID: PMC11415097 DOI: 10.1097/as9.0000000000000456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 05/27/2024] [Indexed: 09/25/2024] Open
Abstract
Objective We explored the oncological impact of tumor deposits (TDs) on colon cancer and proposed optimal modifications to the current staging system. Background In the existing American Joint Committee on Cancer colon cancer staging system, TDs are incorporated into the N category as N1c. When lymph node metastases (LNMs) are present, their number is considered to determine nodal stages, such as N1a/b or N2a/b, regardless of TDs. Methods 4212 patients with primary colon cancer who underwent surgical resection in the Seoul Colorectal Group (2010-2020) and 93,057 patients from the Surveillance, Epidemiology, and End Results*Stat database (2000-2017) were included in this study. Patients were classified according to the number of metastatic lymph nodes (LNs) (0/1-3/≥4) and the presence of TDs. Results TDs were significantly associated with left colon cancer, a higher T category, and vascular/perineural invasion. Patients with TDs had higher recurrence rates (23.1 vs 7.5%, P < 0.001). The TD-positive patients had notably worse overall survival (OS) and recurrence-free survival rates. The survival outcomes of TD-positive patients without LNM were inferior to those of TD-negative patients with LN1-3 (5-year OS: 78.9 vs 87.8%, P = 0.04). The survival outcomes of TD-positive patients with LN1-3 were similar to those of TD-negative patients with LN ≥4 (5-year OS: 87.0 vs 77.1%, P = 0.11). Survival outcomes obtained using the Surveillance, Epidemiology, and End Results *Stat database yielded consistent results. Conclusions TDs were associated with poor prognostic factors and had a significant impact on survival outcomes. The incorporation of tumor deposits into nodal classifications beyond the current N1c criteria may improve the staging system and more accurately reflect the recurrence and survival rates among patients with colon cancer. TD-positive in N1a or N1b could be categorized as N2.
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Affiliation(s)
- Jeeyou Kim
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Woon Lee
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Ji Won Park
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Seung-Bum Ryoo
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Heung-Kwon Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Rumi Shin
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jin Sun Choi
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Min Jung Kim
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Sung-Chan Park
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Duck-Woo Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Seung-Yong Jeong
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
- Department of Surgery, Cancer Research Institute, Seoul National University, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyu Joo Park
- From the Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Colorectal Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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Miao G, Liu J, Zhang Y, Zhou G, Wang F, Huang P, Zhang Y, Wang C, Wang Y, Zeng M, Liu L. A scoring system for stratifying the risk of postoperative bone metastases in colorectal cancer. Surgery 2024; 176:660-667. [PMID: 38890102 DOI: 10.1016/j.surg.2024.04.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/31/2024] [Accepted: 04/29/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND Surveillance recommendations for postoperative high-risk colorectal bone metastases patients remain in a gray area of guidelines. We aimed to develop a risk stratification system to select ideal candidates for follow-up of colorectal bone metastases status. METHODS Postoperative colorectal cancer patients were included to develop a risk-scoring system to predict bone metastases. Risk scores were calculated based on the predictive factors for bone metastases, which were identified using the Cox proportional hazard regression model. Kaplan-Meier curves visualize the differences between risk groups. RESULTS Eight risk factors (age, lymph node metastasis, pathologic tumor deposit, KRAS mutation status, suspicious retroperitoneal lymph node metastasis, lung metastasis status, largest thickness of colorectal cancer lesion, largest short diameter of lymph node) were predictors of colorectal bone metastases and incorporated into the risk scoring system, and the patients were categorized into 2 risk groups. In the low-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 2.4%, 4.6%, and 3.7%, respectively, whereas in the high-risk group, the 1, 3, and 5-year colorectal bone metastases rates were 15.6%, 29.9%, and 44.4%, respectively. The risk scoring system exhibited a C-index of 0.706, 0.795, and 0.841 in 1, 3, and 5 years, respectively. The Kaplan-Meier curve demonstrates that the incidence of colorectal bone metastases was higher in the high-risk group than in the low-risk group (50.5% vs 11.4%, P < .001). CONCLUSION This risk-scoring system may be valuable in predicting colorectal bone metastases in colorectal cancer patients, and we suggest that colorectal bone metastases status surveillance be added in the high-risk group.
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Affiliation(s)
- Gengyun Miao
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Jingjing Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Yang Zhang
- Department of Radiology, Dongying People's Hospital, Shandong, China
| | - Guofeng Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Fang Wang
- Shanghai United Imaging Intelligence Co, Ltd, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Yunfei Zhang
- Shanghai United Imaging Intelligence Co, Ltd, Shanghai, China; Central Research Institute, United Imaging Healthcare, Shanghai, China
| | - Cheng Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Yi Wang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.
| | - Liheng Liu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.
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Firat C, Urganci N, Teplov A, Cesmecioglu E, Bakoglu N, Vakiani E, Ntiamoah P, Weiser MR, Garcia-Aguilar J, Hameed M, Yagi Y, Shia J. Micro-Computed Tomography Whole-Block Imaging Reveals Origin and Path of Rectal Cancer Tumor Deposits: A Pilot Study. Diagnostics (Basel) 2024; 14:1704. [PMID: 39202192 PMCID: PMC11353868 DOI: 10.3390/diagnostics14161704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/01/2024] [Accepted: 08/03/2024] [Indexed: 09/03/2024] Open
Abstract
In colorectal carcinoma (CRC), tumor deposits (TDs) are described as macroscopic/microscopic nests/nodules in the lymph drainage area discontinuous with the primary mass, without identifiable lymph node (LN) tissue, and not confined to vascular or perineural spaces. A TD is categorized as pN1C only when no bona fide LN metastasis exists. However, there has been an ongoing debate on whether TDs should be counted as LNs. The fact that the origin of TDs is not fully understood adds further uncertainty. This pilot study aims to evaluate whether whole-block imaging by micro-computed tomography (micro-CT WBI) that enables three-dimensional reconstruction of whole-mount (WM) blocks can serve as a tool to assess the origin and path of CRC TDs. We evaluated whole-slide imaging (WSI) and micro-CT WBI of 20 WM blocks from a rectal cancer resection that contained TDs. Each TD was tracked through the contiguous blocks to define their origin and path. Of eleven TDs identified on WSI, six were detected on WBI. Strikingly, six of six TDs trackable through the blocks on WBI revealed an origin from the main tumor. This pilot study provided evidence that micro-CT WBI can serve as an effective tool to evaluate the origin and path of CRC TDs.
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Affiliation(s)
- Canan Firat
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Nil Urganci
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Alexei Teplov
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Emine Cesmecioglu
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
- Department of Pathology, Marmara University Research and Education Hospital, Istanbul 34899, Turkey
| | - Nilay Bakoglu
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Peter Ntiamoah
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Meera Hameed
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Yukako Yagi
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (C.F.); (N.U.)
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Chang Z, Fu H, Song J, Kong C, Xie R, Pi M, Sun X, Zhang W, Liu Y, Huang R, Yang T, Han D. The past, present, and future of tumour deposits in colorectal cancer: Advancing staging for improved prognosis and treatment decision-making. J Cell Mol Med 2024; 28:e18562. [PMID: 39189552 PMCID: PMC11348060 DOI: 10.1111/jcmm.18562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/05/2024] [Accepted: 06/27/2024] [Indexed: 08/28/2024] Open
Abstract
Tumour deposits (TDs) significantly impact colorectal cancer (CRC) prognosis. Integrating TDs into the TNM staging system can enhance individualized disease management. Keeping abreast of evolving TDs research is pivotal for clinical advancement. We comprehensively reviewed both recent and popular literature to grasp the field's essence. Subsequently, a data retrieval sourced articles on TDs in CRC for bibliometric analysis, spanning from 1 January 1935 to 30 April 2023. Bibliometrix software facilitated paper analysis and visualization. Bibliometric indicators, the trends and hotspots were determined. A total of 2147 articles were successfully retrieved. Brown G emerged as the most productive author, and the USA as the most prolific country. Central South University and Memorial Sloan Kettering Cancer Center led productivity. Bradford's law categorized 48 journals into zone 1. Keywords co-occurrence analysis identified three main clusters: the application of TDs in TNM staging, the pathogenesis of TDs, and the assessment of TDs. The trend topic analysis highlighted research focused on refining TDs incorporation into tumour staging. TDs wield enduring medical significance, shaping ongoing research. Much literature focused on confirming TD's prognostic value and optimizing TNM integration. Additionally, it is worth highlighting that TD's enigmatic pathogenesis demands research priority, as it holds the potential to unveil concealed knowledge regarding their development.
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Affiliation(s)
- Zhengyan Chang
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Huijun Fu
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Jiaqi Song
- Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Cheng Kong
- Department of Colorectal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
| | - Ruting Xie
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Man Pi
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Xuechen Sun
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Wentao Zhang
- Department of Urology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Yifan Liu
- Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Ruizhi Huang
- Department of Burn SurgeryThe First Affiliated Hospital of Naval Medical UniversityShanghaiChina
| | - Tingsong Yang
- Department of General Surgery, Shanghai Tenth Peoples' HospitalTongji University School of MedicineShanghaiChina
| | - Dongyan Han
- Department of Pathology, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
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Zhu J, Cen W, Zheng X, Ye C, Guo F, Yan X, Shi H, Ye L, Hu T. An internally and externally validated nomogram for predicting cancer-specific survival in octogenarians after radical resection for colorectal cancer. Aging Clin Exp Res 2024; 36:152. [PMID: 39060830 PMCID: PMC11282125 DOI: 10.1007/s40520-024-02809-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 07/09/2024] [Indexed: 07/28/2024]
Abstract
AIMS We aimed to develop an elaborative nomogram that predicts cancer-specific survival (CSS) in American and Chinese octogenarians treated with radical resection for CRC. METHODS The patient data of newly diagnosed patients aged 80 years or older who underwent radical resection for CRC from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly divided into a training cohort and a validation cohort. The patients collected from our hospital were defined as the external validation cohort. Univariate and multivariate Cox regression was used to select independent predictive factors for the construction of a nomogram to predict 1-, 2- and 3-year CSS. RESULTS The multivariate Cox regression model identified age, T stage, N stage, perineural invasion, chemotherapy, tumour deposits, carcinoembryonic antigen level, number of lymph node metastases, and number of solid organ metastases as independent predictors of survival. The C-index of the nomogram for 1-, 2- and 3-year CSS was 0.758, 0.762, and 0.727, respectively, demonstrating significant clinical value and substantial reliability compared to the TNM stage. The calibration curve and area under the curve also indicated considerable predictive accuracy. In addition, decision curve analysis demonstrated desirable net benefits in clinical application. CONCLUSION We constructed a nomogram for predicting the CSS of individual octogenarian patients with CRC who underwent radical resection. The nomogram performed better than the TNM staging system in this particular population and could guide clinicians in clinical follow-up and individual therapeutic plan formulation.
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Affiliation(s)
- Junchang Zhu
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wei Cen
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xuzhi Zheng
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chenqiao Ye
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Feifan Guo
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xialin Yan
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hongying Shi
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China
| | - Lechi Ye
- Department of Colorectal and Anal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Tingting Hu
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Guray Durak M, Gokcay D, Emecen SB, Ozdogan O, Sevinc AI, Ikiz AO, Dogan E, Karabay N, Ellidokuz H, Sarioglu S. Tumor deposits in thyroid carcinomas. Medicine (Baltimore) 2024; 103:e38952. [PMID: 39029040 PMCID: PMC11398754 DOI: 10.1097/md.0000000000038952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/25/2024] [Indexed: 07/21/2024] Open
Abstract
Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4-341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.
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Affiliation(s)
- Merih Guray Durak
- Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Deniz Gokcay
- Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Serra Begum Emecen
- Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ozhan Ozdogan
- Department of Nuclear Medicine, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ali Ibrahim Sevinc
- Department of General Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ahmet Omer Ikiz
- Department of Ear, Nose, Throat and Head & Neck Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Ersoy Dogan
- Department of Ear, Nose, Throat and Head & Neck Surgery, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Nuri Karabay
- Department of Radiology, Dokuz Eylul University School of Medicine, Izmir, Turkey
| | - Hulya Ellidokuz
- Department of Preventive Oncology, Dokuz Eylul University Institute of Oncology, Izmir, Turkey
| | - Sulen Sarioglu
- Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey
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Knight K, Bigley C, Pennel K, Hay J, Maka N, McMillan D, Park J, Roxburgh C, Edwards J. The Glasgow Microenvironment Score: an exemplar of contemporary biomarker evolution in colorectal cancer. J Pathol Clin Res 2024; 10:e12385. [PMID: 38853386 PMCID: PMC11163018 DOI: 10.1002/2056-4538.12385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/11/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024]
Abstract
Colorectal cancer remains a leading cause of mortality worldwide. Significant variation in response to treatment and survival is evident among patients with similar stage disease. Molecular profiling has highlighted the heterogeneity of colorectal cancer but has had limited impact in daily clinical practice. Biomarkers with robust prognostic and therapeutic relevance are urgently required. Ideally, biomarkers would be derived from H&E sections used for routine pathological staging, have reliable sensitivity and specificity, and require minimal additional training. The biomarker targets would capture key pathological features with proven additive prognostic and clinical utility, such as the local inflammatory response and tumour microenvironment. The Glasgow Microenvironment Score (GMS), first described in 2014, combines assessment of peritumoural inflammation at the invasive margin with quantification of tumour stromal content. Using H&E sections, the Klintrup-Mäkinen (KM) grade is determined by qualitative morphological assessment of the peritumoural lymphocytic infiltrate at the invasive margin and tumour stroma percentage (TSP) calculated in a semi-quantitative manner as a percentage of stroma within the visible field. The resulting three prognostic categories have direct clinical relevance: GMS 0 denotes a tumour with a dense inflammatory infiltrate/high KM grade at the invasive margin and improved survival; GMS 1 represents weak inflammatory response and low TSP associated with intermediate survival; and GMS 2 tumours are typified by a weak inflammatory response, high TSP, and inferior survival. The prognostic capacity of the GMS has been widely validated while its potential to guide chemotherapy has been demonstrated in a large phase 3 trial cohort. Here, we detail its journey from conception through validation to clinical translation and outline the future for this promising and practical biomarker.
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Affiliation(s)
- Katrina Knight
- Academic Unit of Surgery, Glasgow Royal Infirmary, School of Medicine, Dentistry and NursingUniversity of GlasgowGlasgowUK
| | | | | | - Jennifer Hay
- Glasgow Tissue Research FacilityQueen Elizabeth University HospitalGlasgowUK
| | - Noori Maka
- Department of PathologyQueen Elizabeth University HospitalGlasgowUK
| | - Donald McMillan
- Academic Unit of Surgery, Glasgow Royal Infirmary, School of Medicine, Dentistry and NursingUniversity of GlasgowGlasgowUK
| | - James Park
- Academic Unit of Surgery, Glasgow Royal Infirmary, School of Medicine, Dentistry and NursingUniversity of GlasgowGlasgowUK
- Department of SurgeryQueen Elizabeth University HospitalGlasgowUK
| | - Campbell Roxburgh
- Academic Unit of Surgery, Glasgow Royal Infirmary, School of Medicine, Dentistry and NursingUniversity of GlasgowGlasgowUK
- School of Cancer SciencesUniversity of GlasgowGlasgowUK
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Guo Z, Zhang Z, Liu L, Zhao Y, Liu Z, Zhang C, Qi H, Feng J, Yang C, Tai W, Banchini F, Inchingolo R. Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108362. [PMID: 38704899 DOI: 10.1016/j.ejso.2024.108362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 04/11/2024] [Accepted: 04/20/2024] [Indexed: 05/07/2024]
Abstract
OBJECTIVE This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.
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Affiliation(s)
- Zhentian Guo
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Zongming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China.
| | - Limin Liu
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Yue Zhao
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Zhuo Liu
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Chong Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Hui Qi
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China; Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China
| | - Jinqiu Feng
- Key Laboratory of Geriatrics (Hepatobiliary Diseases) of China General Technology Group, Beijing, 100073, China; Department of Immunology, Peking University School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Chunmin Yang
- Department of Gastroenterology, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, 100073, China
| | - Weiping Tai
- Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Filippo Banchini
- General Surgery Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, "F. Miulli" Regional General Hospital, Acquaviva delle Fonti, 70021, Italy
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Zheng Z, Luo H, Deng K, Li Q, Xu Q, Liu K. Evaluating the prognostic value of tumor deposits in non-metastatic lymph node-positive colon adenocarcinoma using Cox regression and machine learning. Int J Colorectal Dis 2024; 39:97. [PMID: 38922361 PMCID: PMC11208197 DOI: 10.1007/s00384-024-04671-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/14/2024] [Indexed: 06/27/2024]
Abstract
BACKGROUND The 8th AJCC TNM staging for non-metastatic lymph node-positive colon adenocarcinoma patients(NMLP-CA) stages solely by lymph node status, irrespective of the positivity of tumor deposits (TD). This study uses machine learning and Cox regression to predict the prognostic value of tumor deposits in NMLP-CA. METHODS Patient data from the SEER registry (2010-2019) was used to develop CSS nomograms based on prognostic factors identified via multivariate Cox regression. Model performance was evaluated by c-index, dynamic calibration, and Schmid score. Shapley additive explanations (SHAP) were used to explain the selected models. RESULTS The study included 16,548 NMLP-CA patients, randomized 7:3 into training (n = 11,584) and test (n = 4964) sets. Multivariate Cox analysis identified TD, age, marital status, primary site, grade, pT stage, and pN stage as prognostic for cancer-specific survival (CSS). In the test set, the gradient boosting machine (GBM) model achieved the best C-index (0.733) for CSS prediction, while the Cox model and GAMBoost model optimized dynamic calibration(6.473) and Schmid score (0.285), respectively. TD ranked among the top 3 most important features in the models, with increasing predictive significance over time. CONCLUSIONS Positive tumor deposit status confers worse prognosis in NMLP-CA patients. Tumor deposits may confer higher TNM staging. Furthermore, TD could play a more significant role in the staging system.
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Affiliation(s)
- Zhen Zheng
- Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, 57 Xingning RoadZhejiang Province, Ningbo, China
| | - Hui Luo
- Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, 57 Xingning RoadZhejiang Province, Ningbo, China
| | - Ke Deng
- Department of Colorectal Surgery, The Affiliated Lihuili Hospital of Ningbo University, Zhejiang Province, Ningbo, China
| | - Qun Li
- Department of Otolaryngology Head and Neck Surgery, The Affiliated Lihuili Hospital of Ningbo University, Zhejiang Province, Ningbo, China
| | - Quan Xu
- Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, 57 Xingning RoadZhejiang Province, Ningbo, China
| | - Kaitai Liu
- Department of Chemoradiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, 57 Xingning RoadZhejiang Province, Ningbo, China.
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Salmerón-Ruiz A, Luengo Gómez D, Medina Benítez A, Láinez Ramos-Bossini AJ. Primary staging of rectal cancer on MRI: an updated pictorial review with focus on common pitfalls and current controversies. Eur J Radiol 2024; 175:111417. [PMID: 38484688 DOI: 10.1016/j.ejrad.2024.111417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/23/2024] [Accepted: 03/06/2024] [Indexed: 10/04/2024]
Abstract
Magnetic resonance imaging (MRI) plays a pivotal role in primary staging of rectal cancer, enabling the determination of appropriate management strategies and prediction of patient outcomes. However, inconsistencies and pitfalls exist in various aspects, including rectal anatomy, MRI protocols and strategies for artifact resolution, as well as in T- and N-staging, all of which limit the diagnostic value of MRI. This narrative and pictorial review offers a comprehensive overview of factors influencing primary staging of rectal cancer and the role of MRI in assessing them. It highlights the significance of the circumferential resection margin and its relationship with the mesorectal fascia, as well as the prognostic role of extramural venous invasion and tumor deposits. Special attention is given to tumors of the lower rectum due to their complex anatomy and the challenges they pose in MRI staging. The review also addresses current controversies in rectal cancer staging and the need for personalized risk stratification. In summary, this review provides valuable insights into the role of MRI in the primary staging of rectal cancer, emphasizing key aspects for accurate assessment to enhance patient outcomes.
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Affiliation(s)
- A Salmerón-Ruiz
- Abdominal Radiology Section. Department of Radiology, Hospital Universitario Virgen de las Nieves, 18014. Granada, Spain; Advanced Medical Imaging Group (TeCe22), Instituto Biosanitario de Granada (ibs.GRANADA). 18016 Granada, Spain
| | - D Luengo Gómez
- Abdominal Radiology Section. Department of Radiology, Hospital Universitario Virgen de las Nieves, 18014. Granada, Spain; Advanced Medical Imaging Group (TeCe22), Instituto Biosanitario de Granada (ibs.GRANADA). 18016 Granada, Spain
| | - A Medina Benítez
- Abdominal Radiology Section. Department of Radiology, Hospital Universitario Virgen de las Nieves, 18014. Granada, Spain
| | - A J Láinez Ramos-Bossini
- Abdominal Radiology Section. Department of Radiology, Hospital Universitario Virgen de las Nieves, 18014. Granada, Spain; Advanced Medical Imaging Group (TeCe22), Instituto Biosanitario de Granada (ibs.GRANADA). 18016 Granada, Spain.
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Sun Z, Xia F, Lv W, Li J, Zou Y, Wu J. Radiomics based on T2-weighted and diffusion-weighted MR imaging for preoperative prediction of tumor deposits in rectal cancer. Am J Surg 2024; 232:59-67. [PMID: 38272767 DOI: 10.1016/j.amjsurg.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/17/2023] [Accepted: 01/03/2024] [Indexed: 01/27/2024]
Abstract
AIM Preoperative diagnosis of tumor deposits (TDs) in patients with rectal cancer remains a challenge. This study aims to develop and validate a radiomics nomogram based on the combination of T2-weighted (T2WI) and diffusion-weighted MR imaging (DWI) for the preoperative identification of TDs in rectal cancer. MATERIALS AND METHODS A total of 199 patients with rectal cancer who underwent T2WI and DWI were retrospectively enrolled and divided into a training set (n = 159) and a validation set (n = 40). The total incidence of TDs was 37.2 % (74/199). Radiomics features were extracted from T2WI and apparent diffusion coefficient (ADC) images. A radiomics nomogram combining Rad-score (T2WI + ADC) and clinical factors was subsequently constructed. The area under the receiver operating characteristic curve (AUC) was then calculated to evaluate the models. The nomogram is also compared to three machine learning model constructed based on no-Rad scores. RESULTS The Rad-score (T2WI + ADC) achieved an AUC of 0.831 in the training and 0.859 in the validation set. The radiomics nomogram (the combined model), incorporating the Rad-score (T2WI + ADC), MRI-reported lymph node status (mLN-status), and CA19-9, showed good discrimination of TDs with an AUC of 0.854 for the training and 0.923 for the validation set, which was superior to Random Forests, Support Vector Machines, and Deep Learning models. The combined model for predicting TDs outperformed the other three machine learning models showed an accuracy of 82.5 % in the validation set, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 66.7 %, 92.0 %, 83.3 %, and 82.1 %, respectively. CONCLUSION The radiomics nomogram based on Rad-score (T2WI + ADC) and clinical factors provides a promising and effective method for the preoperative prediction of TDs in patients with rectal cancer.
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Affiliation(s)
- Zhen Sun
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Tongji Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Feng Xia
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenzhi Lv
- Department of Artificial Intelligence, Julei Technology Company, Wuhan, 430030, China
| | - Jin Li
- Computer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - You Zou
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Tongji Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jianhong Wu
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Tongji Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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Karahacioglu D, Taskin OC, Esmer R, Armutlu A, Saka B, Ozata IH, Rencuzogullari A, Bugra D, Balik E, Adsay V, Gurses B. Performance of CT in the locoregional staging of colon cancer: detailed radiology-pathology correlation with special emphasis on tumor deposits, extramural venous invasion and T staging. Abdom Radiol (NY) 2024; 49:1792-1804. [PMID: 38446179 DOI: 10.1007/s00261-024-04203-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 01/03/2024] [Accepted: 01/12/2024] [Indexed: 03/07/2024]
Abstract
PURPOSE To investigate the performance of computed tomography (CT) in the local staging of colon cancer in different segments, with emphasis on parameters that have been found to be significant for rectal cancer, namely, extramural venous invasion (EMVI) and tumor deposits (TDs). METHODS CT and pathology data from 137 patients were independently reviewed by radiology and pathology teams. The performance of CT in categorizing a given patient into good, versus poor prognostic groups was assessed for each segment, as well as the presence of lymph nodes (LNs), TDs and EMVIs. Discordant cases were re-evaluated to determine potential sources of error. Elastic stain was applied for EMVI discordance. RESULTS The T staging accuracy was 80.2%. For T stage stratification, CT performed slightly better in the left colon, and the lowest accuracy was in the transverse colon. Under-staging was more common (in 12.4%), and most of the mis-staged cases were in sigmoid colon. According to the first comprehensive correlative analysis, the sensitivity, specificity, and accuracy of CT for detecting TDs were found to be 57.9%, 92.4%, 87.6%, respectively. These figures were 44.7%, 72.7%, and 63.5% for LN, and 58.5%, 82.1% and 73% for EMVI. The detection rate was better for multifocal EMVI. The detection rate was also comparable (although substantially underestimated) for LNs, with the half of the LNs missed by CT being < 5 mm. Four patients that were classified as TD by CT, disclosed to be LNs by pathology. Correlative analysis led to refinement of the pathology criteria, with subsequent modifications of the initial reports in 13 (9.5%) patients. CONCLUSION Overall, CT performed well in the evaluation of colon cancer, as did TD and EMVI. It is advisable to include these parameters in CT-based staging. Radiologists should be aware of the pitfalls that occur more commonly in different segments.
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Affiliation(s)
- Duygu Karahacioglu
- Department of Radiology, Koç University School of Medicine, 34010, Istanbul, Turkey.
| | - Orhun Cig Taskin
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Rohat Esmer
- Koç University School of Medicine, Istanbul, Turkey
| | - Ayse Armutlu
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Burcu Saka
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Ibrahim Halil Ozata
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Ahmet Rencuzogullari
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Dursun Bugra
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Emre Balik
- Department of General Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Bengi Gurses
- Department of Radiology, Koç University School of Medicine, 34010, Istanbul, Turkey
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Que YT, Chen Y, Yang XY, Ma YR, Liu YY, Wen ZQ, Lu BL, Wu XH, Zhang ZW, Wu YZ, Yu SP, Yuan JP. MRI-detected tumor deposits in cT3 and cT4 rectal cancer following neoadjuvant chemoradiotherapy. Eur Radiol 2024; 34:2963-2973. [PMID: 37840101 DOI: 10.1007/s00330-023-10261-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 07/06/2023] [Accepted: 07/23/2023] [Indexed: 10/17/2023]
Abstract
OBJECTIVES To evaluate the identification of tumor deposits (TDs) and the prognostic significance of an MRI tumor regression grade for TDs in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). METHODS Ninety-one patients with cT3 or cT4 rectal cancer who underwent surgery following nCRT between August 2014 and June 2020 were retrospectively analyzed. Changes in pre-nCRT MRI-detected TDs (mrTDs) were described as mrTD regression grade. The diagnostic performance of post-nCRT MRI-detected TDs (ymrTDs) was compared with histopathological reference standard. The correlation between ymrTDs, mrTD regression grade, and disease-free survival (DFS) was assessed. RESULTS The sensitivity and specificity of ymrTDs were 88.00% and 89.39%, respectively. The area under the receiver operating characteristic curve was 0.887 (95% confidence interval [CI]: 0.803-0.944). The 3-year DFS of patients with positive ymrTDs was significantly lower than of the negative group (44.83% vs 82.73%, p < 0.001). The 3-year DFS was 33.33% for patients with poor regression of mrTDs following nCRT and 55.56% for those with moderate regression, compared to 69.23% in good responders and 83.97% in patients without mrTDs (p < 0.001). On multivariable Cox regression, mrTD regression grade was the only independent MRI factor associated with DFS (p = 0.042). CONCLUSIONS Diagnostic performance of ymrTDs was moderate. The mrTD regression grade was independently correlated with DFS, which may have a prognostic implication for treatment and follow-up. CLINICAL RELEVANCE STATEMENT Patients with poor regression of MRI-detected tumor deposits may benefit from more aggressive treatments, such as chemoradiation therapy plus induction or consolidation chemotherapy. KEY POINTS • MRI provides a preoperative and noninvasive way to visualize tumor deposits (TDs) after neoadjuvant chemoradiotherapy (nCRT). • Post-nCRT MRI-detected TDs are a poor prognostic marker in cT3 and cT4 rectal cancer patients. • The regression of MRI-detected TDs after nCRT is associated with an improved disease-free survival.
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Affiliation(s)
- Yu-Tao Que
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
- Department of Radiology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangming District, No. 628, Zhenyuan Road, Shenzhen, 518107, China
| | - Yan Chen
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Xin-Yue Yang
- Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Yu-Ru Ma
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Yi-Yan Liu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Zi-Qiang Wen
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Bao-Lan Lu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Xue-Han Wu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
- Department of Radiology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangming District, No. 628, Zhenyuan Road, Shenzhen, 518107, China
| | - Zhi-Wen Zhang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China
| | - Yun-Zhu Wu
- MR Scientific Marketing, SIEMENS Healthineers Ltd, Shanghai, 210031, China
| | - Shen-Ping Yu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Yuexiu District, No. 58, Zhongshan Second Road, Guangzhou, 510080, China.
| | - Jian-Peng Yuan
- Department of Radiology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangming District, No. 628, Zhenyuan Road, Shenzhen, 518107, China.
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Gonzalez RS, La Rosa S, Ma C, Polydorides AD, Shi C, Yang Z, Cox B, Karamchandani DM. Debating Deposits, Redux: Substantial Interobserver Agreement Exists in Distinguishing Tumor Deposits From Nodal Metastases in Small Bowel Neuroendocrine Tumors. Arch Pathol Lab Med 2024; 148:581-587. [PMID: 37639446 DOI: 10.5858/arpa.2023-0169-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2023] [Indexed: 08/31/2023]
Abstract
CONTEXT Recent data suggest mesenteric tumor deposits (MTDs) indicate poor prognosis in small bowel well-differentiated neuroendocrine tumors (SB-NETs), including compared to positive lymph nodes, making their distinction crucial. OBJECTIVE To study interobserver agreement in distinguishing SB-NET MTDs from positive nodes. DESIGN Virtual slides from 36 locally metastatic SB-NET foci were shared among 7 gastrointestinal pathologists, who interpreted each as an MTD or a positive node. Observers ranked their 5 preferred choices among a supplied list of potentially useful histologic features, for both options. Diagnostic opinions were compared using Fleiss multirater and Cohen weighted κ analyses. RESULTS Preferred criteria for MTD included irregular shape (n = 7, top choice for 5), perineural invasion/nerve entrapment (n = 7, top choice for 2), encased thick-walled vessels (n = 7), and prominent fibrosis (n = 6). Preferred criteria for positive nodes included peripheral lymphoid follicles (n = 6, top choice for 4), round shape (n = 7, top choice for 2), peripheral lymphocyte rim (n = 7, top choice for 1), subcapsular sinuses (n = 7), and a capsule (n = 6). Among 36 foci, 10 (28%) each were unanimously diagnosed as MTD or positive node. For 13 foci (36%), there was a diagnosis favored by most observers (5 or 6 of 7): positive node in 8, MTD in 5. Only 3 cases (8%) had a near-even (4:3) split. Overall agreement was substantial (κ = .64, P < .001). CONCLUSIONS Substantial interobserver agreement exists for distinguishing SB-NET MTDs from lymph node metastases. Favored histologic criteria in making the distinction include irregular shape and nerve/vessel entrapment for MTD, and peripheral lymphocytes/lymphoid follicles and round shape for positive nodes.
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Affiliation(s)
- Raul S Gonzalez
- From the Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia (Gonzalez)
| | - Stefano La Rosa
- Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy (La Rosa)
| | - Changqing Ma
- Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri (Ma)
| | - Alexandros D Polydorides
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York (Polydorides)
| | - Chanjuan Shi
- Department of Pathology, Duke University Medical Center, Durham, North Carolina (Shi)
| | - Zhaohai Yang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (Yang)
| | - Brian Cox
- Pacific Rim Pathology, San Diego, California (Cox)
| | - Dipti M Karamchandani
- the Department of Pathology, UT Southwestern Medical Center, Dallas, Texas (Karamchandani)
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Wang R, Yan Z. Cancer spreading patterns based on epithelial-mesenchymal plasticity. Front Cell Dev Biol 2024; 12:1259953. [PMID: 38665432 PMCID: PMC11043583 DOI: 10.3389/fcell.2024.1259953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
Introduction: Metastasis is a major cause of cancer-related deaths, underscoring the necessity to discern the rules and patterns of cancer cell spreading. Epithelial-mesenchymal plasticity contributes to cancer aggressiveness and metastasis. Despite establishing key determinants of cancer aggressiveness and metastatic ability, a comprehensive understanding of the underlying mechanism is unknown. We aimed to propose a classification system for cancer cells based on epithelial-mesenchymal plasticity, focusing on hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype. Methods: We extensively reviewed the concept of epithelial-mesenchymal plasticity, specifically considering the hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype. Results: In this review and hypothesis article, based on epithelial-mesenchymal plasticity, especially the hysteresis of epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype, we proposed a classification of cancer cells, indicating that cancer cells with epithelial-mesenchymal plasticity potential could be classified into four types: irreversible hysteresis, weak hysteresis, strong hysteresis, and hybrid epithelial/mesenchymal phenotype. These four types of cancer cells had varied biology, spreading features, and prognoses. Discussion: Our results highlight that the proposed classification system offers insights into the diverse behaviors of cancer cells, providing implications for cancer aggressiveness and metastasis.
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Affiliation(s)
- Rui Wang
- Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhaopeng Yan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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Hakki L, Khan A, Do E, Gonen M, Firat C, Vakiani E, Shia J, Widmar M, Wei IH, Smith JJ, Pappou EP, Nash GM, Paty PB, Garcia-Aguilar J, Weiser MR. Tumour deposits are independently associated with recurrence in colon cancer. Colorectal Dis 2024; 26:459-465. [PMID: 38263577 PMCID: PMC10981558 DOI: 10.1111/codi.16873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/22/2023] [Accepted: 12/10/2023] [Indexed: 01/25/2024]
Abstract
AIM Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.
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Affiliation(s)
- Lynn Hakki
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Asama Khan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Eric Do
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Canan Firat
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Maria Widmar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Iris H Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - J Joshua Smith
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Emmanouil P Pappou
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Garrett M Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Philip B Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Martin R Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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46
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Jiang C, Shen Y, Xu C, Liu Y, Zhou H, Xu Q, Gu L. Clinical and Pathologic Predictors of Tumor Deposits in Colorectal Cancer. J Gastrointest Cancer 2024; 55:182-187. [PMID: 38051392 DOI: 10.1007/s12029-023-00988-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND Tumor deposits (TDs) are a special metastatic pattern of colorectal cancer (CRC). This study aims to explore the pathological characteristics of TD and find out the risk factors of TD in CRC. METHODS TDs cases of CRC were selected and validated by HE staining. The correlation between TDs and T stages, N stages, and microsatellite instability was calculated by the chi-squared (χ2) test. RESULTS A total of 2553 patients with colorectal cancer undergoing intestinal resection were included in this study. Two hundred fifty-nine cases of TDs patients were included. The positive rate of TDs was 1.9% (2/105) in T1, 3.8% (10/266) in T2, 11% (231/2305) in T3, and 22.8% (16/77) in T4. T3 and T4 were more prone to TDs than T1 and T2, but there was no difference between T3 and T4. The positive rate of TDs was 7.2% (107/1491) in N0, 14.3% (152/1062) in N + , and N + was more prone to TDs than N0. The positive rate of TDs was 10.5% (256/2432) in MSS, 2.5% (3/121) in MSI, and MSS was more prone to TDs than MSI. Multivariate analysis showed lymph node invasion, T stage, and MSS were independent risk factors for TDs. CONCLUSION Lymph node invasion, T stage, and MSS were independent risk factors for TDs.
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Affiliation(s)
- Chunhui Jiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Yanying Shen
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Ye Liu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Hong Zhou
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
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Stefanou AJ. Surgical and Interventional Management of Lung Metastasis: Surgical Assessment, Resection, Ablation, Percutaneous Interventions. Clin Colon Rectal Surg 2024; 37:85-89. [PMID: 38322599 PMCID: PMC10843877 DOI: 10.1055/s-0042-1758823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
The lungs are the second most common site of metastases for colorectal cancer after the liver. Pulmonary metastases can be identified at the time of diagnosis of the primary tumor, or metachronously. About 20% of patients with colorectal cancer will develop pulmonary metastases. The best options for treatment include a multidisciplinary treatment approach consisting of surgical resection whenever possible, and chemotherapy. Surgical options most often include minimally invasive segmentectomy or wedge resection, while patients unable to have surgery may benefit from radio frequency ablation or radiation treatment. Prognosis is dependent on preoperative carcinoembryonic antigen level, number, and location of metastatic lesions, and resectability of primary tumor. Overall, pulmonary metastases are best treated by complete resection whenever possible.
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Affiliation(s)
- Amalia J. Stefanou
- Gastrointestinal Oncology, Surgical Oncology, Moffitt Cancer Center, Tampa, Florida
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48
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Boute TC, Swartjes H, Greuter MJ, Elferink MA, van Eekelen R, Vink GR, de Wilt JH, Coupé VM. Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II-III Colorectal Cancer: A Population-based Study. CANCER RESEARCH COMMUNICATIONS 2024; 4:607-616. [PMID: 38363145 PMCID: PMC10903299 DOI: 10.1158/2767-9764.crc-23-0512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/07/2024] [Accepted: 02/12/2024] [Indexed: 02/17/2024]
Abstract
Real-world data are necessitated to counsel patients about the risk for recurrent disease after curative treatment of colorectal cancer. This study provided a population-based overview of the epidemiology of recurrent disease in patients with surgically resected stage II/III colorectal cancer.Patients diagnosed with stage II/III primary colorectal cancer between July and December 2015 were selected from the Netherlands Cancer Registry (N = 3,762). Cumulative incidence of recurrent disease was estimated, and multivariable competing risk regression was used to identify risk factors for recurrent disease in patients with primary colon and rectal cancer. Moreover, overall survival (OS) after diagnosis of recurrent colorectal cancer was estimated.Median clinical follow-up was 58 months (Q1-Q3: 22-62). Five-year cumulative incidence of recurrent disease was 21.6% [95% confidence interval (CI): 20.0-23.2] and 30.0% (95% CI: 28.3-33.5) for patients with primary colon and rectal cancer, respectively. Stage III disease and incomplete resection margin in patients with primary colon cancer and extramural vascular invasion in patients with primary rectal cancer were strongly (HR ≥ 2) associated with recurrent disease. Median OS of patients with distant, locoregional, or the synchronous combination of distant and locoregional recurrent disease was 29, 27, and 13 months, respectively (P < 0.001). Patients with distant recurrences limited to liver or lung showed a median OS of 46 and 48 months, respectively. The incidence of recurrent disease was higher in patients with rectal cancer than in patients with colon cancer, predominantly due to higher rates of distant recurrences. OS after recurrent disease was impaired, but subgroups of patients diagnosed with recurrent disease limited to one site showed statistically significantly longer OS. SIGNIFICANCE Population-based data on recurrent colorectal cancer are rare, but crucial for counseling patients and their physicians. This large nationwide, population-based study provides an up-to-date overview of the epidemiology of recurrent disease in patients with stage II and III primary colon and rectal cancer treated with surgical resection.
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Affiliation(s)
- Tara C. Boute
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands
| | - Hidde Swartjes
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marjolein J.E. Greuter
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands
| | - Marloes A.G. Elferink
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands
| | - Rik van Eekelen
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands
| | - Geraldine R. Vink
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | | | - Veerle M.H. Coupé
- Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands
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Mubarak M, Rashid R, Shakeel S. Tumor deposits in axillary adipose tissue in patients with breast cancer: Do they matter? World J Clin Cases 2024; 12:1045-1049. [PMID: 38464926 PMCID: PMC10921311 DOI: 10.12998/wjcc.v12.i6.1045] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/10/2024] [Accepted: 01/31/2024] [Indexed: 02/20/2024] Open
Abstract
Tumor deposits (TDs) are defined as discrete, irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor, and are usually found in the lymphatic drainage area of the primary tumor. By definition, no residual lymph node structure should be identified in these tumor masses. At present, TDs are mainly reported in colorectal cancer, with a few reports in gastric cancer. There are very few reports on breast cancer (BC). For TDs, current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue. Even some pathologists classify a TD as two lymph node metastases for calculation. Some pathologists also believe that TDs belong to the category of disseminated metastasis. Therefore, regardless of the origin, TDs are an indicator of poor prognosis. Moreover, for BC, sentinel lymph node biopsy is generally used at present. Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive. The present commentary of this clinical issue has certain guiding significance. It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.
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Affiliation(s)
- Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Rahma Rashid
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Shaheera Shakeel
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
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Khan A, Thompson H, Hsu M, Widmar M, Wei IH, Pappou E, Smith JJ, Nash GM, Paty PB, Garcia-Aguilar J, Shia J, Gonen M, Weiser MR. Validation of a Clinical Calculator Predicting Freedom From Colon Cancer Recurrence After Surgery on the Basis of Molecular and Clinical Variables. Dis Colon Rectum 2024; 67:240-245. [PMID: 37815326 PMCID: PMC10843082 DOI: 10.1097/dcr.0000000000002896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
BACKGROUND The Memorial Sloan Kettering clinical calculator for estimating the likelihood of freedom from colon cancer recurrence on the basis of clinical and molecular variables was developed at a time when testing for microsatellite instability was performed selectively, based on patient age, family history, and histologic features. Microsatellite stability was assumed if no testing was done. OBJECTIVE This study aimed to validate the calculator in a cohort of patients who had all been tested for microsatellite instability. DESIGN Retrospective cohort analysis. SETTINGS Comprehensive cancer center. PATIENTS This study included consecutive patients who underwent curative resection for stage I, II, or III colon cancer between 2017 and 2019. INTERVENTION Universal testing of mircrosatellite phenotype in all cases. MAIN OUTCOME MEASURES The calculator's predictive accuracy was assessed using the concordance index and a calibration plot of predicted versus actual freedom from recurrence at 3 years after surgery. For a secondary sensitivity analysis, the presence of a tumor deposit(s) (disease category N1c) was considered equivalent to one positive lymph node (category N1a). RESULTS With a median follow-up of 32 months among survivors, the concordance index for the 745 patients in the cohort was 0.748 (95% CI, 0.693-0.801), and a plot of predicted versus observed recurrences approached the 45° diagonal, indicating good discrimination and calibration. In the secondary sensitivity analysis for tumor deposits, the concordance index was 0.755 (95% CI, 0.700-0.806). LIMITATIONS This study was limited by its retrospective, single-institution design. CONCLUSIONS These results, based on inclusion of actual rather than imputed microsatellite stability status and presence of tumor deposits, confirm the predictive accuracy and reliability of the calculator. See Video Abstract . VALIDACIN DE UNA CALCULADORA CLNICA QUE PREDICE LA AUSENCIA DE RECURRENCIA POSTQUIRURGICA DEL CNCER DE COLON SOBRE LA BASE DE VARIABLES MOLECULARES Y CLNICAS ANTECEDENTES:La calculadora clínica del Memorial Sloan Kettering para la estimación de la probabilidad de ausencia de recurrencia del cáncer de colon sobre la base de variables clínicas y moleculares, se desarrolló en un momento en que las pruebas para la inestabilidad de microsatélites se realizaban de forma selectiva, basadas en la edad del paciente, los antecedentes familiares y las características histológicas. Se asumía la estabilidad micro satelital si no se realizaba ninguna prueba.OBJETIVO:El objetivo de este estudio fue validar la calculadora en una cohorte de pacientes a los que se les había realizado la prueba de inestabilidad de microsatélites.DISEÑO:Análisis de cohorte retrospectivo.AJUSTE:Centro integral de cáncer.PACIENTES:Pacientes consecutivos con cáncer de colon que fueron sometidos a resección curativa por cáncer de colon en estadios I, II o III entre los años 2017 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:La precisión predictiva de la calculadora fue evaluada mediante el índice de concordancia y un gráfico de calibración de la ausencia de recurrencia predecida versus la real a los 3 años tras la cirugía. A los efectos de un análisis secundario de sensibilidad, la presencia de depósito(s) tumoral(es) (categoría de enfermedad N1c) se consideró equivalente a un ganglio linfático positivo (categoría N1a).RESULTADOS:Con una mediana de seguimiento de 32 meses entre los supervivientes, el índice de concordancia para los 745 pacientes de la cohorte fue de 0,748 (intervalo de confianza del 95 %, 0,693 a 0,801), y una gráfica de recurrencias previstas versus observadas se acercó a la diagonal de 45°, indicando una buena discriminación y calibración. En el análisis secundario de sensibilidad para depósitos tumorales, el índice de concordancia fue de 0,755 (intervalo de confianza del 95 %, 0,700 a 0,806).LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Estos resultados, basados en la inclusión real del estado de estabilidad de microsatélites en lugar de imputado y la presencia de depósitos tumorales, confirman la precisión predictiva y la confiabilidad de la calculadora. (Traducción-Dr Osvaldo Gauto ).
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Affiliation(s)
- Asama Khan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Hannah Thompson
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Meier Hsu
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York
| | - Maria Widmar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Iris H. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Emmanouil Pappou
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - J. Joshua Smith
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Garrett M. Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | - Philip B. Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
| | | | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York
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