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Cotan HT, Emilescu RA, Iaciu CI, Orlov-Slavu CM, Olaru MC, Popa AM, Jinga M, Nitipir C, Schreiner OD, Ciobanu RC. Prognostic and Predictive Determinants of Colorectal Cancer: A Comprehensive Review. Cancers (Basel) 2024; 16:3928. [PMID: 39682117 DOI: 10.3390/cancers16233928] [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: 11/06/2024] [Revised: 11/20/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health burden, necessitating a thorough understanding of prognostic and predictive factors to enhance patient outcomes. This systematic review aims to comprehensively evaluate prognostic and predictive determinants in CRC, encompassing both traditional and emerging biomarkers. A systematic search of major electronic databases was conducted to identify relevant studies published from 1995 up to 2024. Eligible articles were critically appraised, and data extraction was performed according to predefined criteria. The prognostic determinants examined included clinicopathological features such as tumor stage, grade, and lymph node involvement, as well as molecular biomarkers including RAS, BRAF, and MSI status. Predictive determinants encompassed biomarkers influencing response to targeted therapies and immunotherapy, such as HER2 and Immunoscore. The review also explores novel prognostic and predictive markers, including tumor microenvironment characteristics and liquid biopsy-based biomarkers. Synthesizing evidence from diverse studies, this review provides insights into the prognostic and predictive landscape of CRC, highlighting the potential clinical implications of identified determinants. Understanding the multifaceted nature of prognostic and predictive factors in CRC is imperative for the advancement of personalized treatment strategies and improvement of patient outcomes.
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Affiliation(s)
- Horia T Cotan
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Radu A Emilescu
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Cristian I Iaciu
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Cristina M Orlov-Slavu
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Mihaela C Olaru
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Ana M Popa
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Mariana Jinga
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Cornelia Nitipir
- General Medicine Faculty, Carol Davila University of Medicine and Pharmacy, 8 Sanitary Heroes Boulevard, 050474 Bucharest, Romania
| | - Oliver Daniel Schreiner
- Regional Institute of Oncology Iasi, 2-4 General Henri Mathias Berthelot Street, 700483 Iasi, Romania
- Department 3-Medical Sciences, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania
- Department of Electrical Measurements and Materials, Gheorghe Asachi Technical University, 700050 Iasi, Romania
| | - Romeo Cristian Ciobanu
- Department of Electrical Measurements and Materials, Gheorghe Asachi Technical University, 700050 Iasi, Romania
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Wang H, Zhang J, Li Y, Wang D, Zhang T, Yang F, Li Y, Zhang Y, Yang L, Li P. Deep-learning features based on F18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) to predict preoperative colorectal cancer lymph node metastasis. Clin Radiol 2024; 79:e1152-e1158. [PMID: 38955636 DOI: 10.1016/j.crad.2024.05.017] [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: 10/13/2023] [Revised: 04/04/2024] [Accepted: 05/24/2024] [Indexed: 07/04/2024]
Abstract
AIM The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features. MATERIALS AND METHODS In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis. RESULTS The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort. CONCLUSION We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.
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Affiliation(s)
- H Wang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - J Zhang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - Y Li
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - D Wang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - T Zhang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - F Yang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - Y Li
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - Y Zhang
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - L Yang
- PET/MR Department, Harbin Medical University Cancer Hospital, Haping Road, Nangang District, Harbin, Heilongjiang Province, China.
| | - P Li
- Department of PET/CT, The Second Affiliated Hospital of Harbin Medical University, Baojian Road, Nangang District, Harbin, Heilongjiang Province, China.
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Liu B, Zhang ZX, Nie XY, Sun WL, Yan YJ, Fu WH. Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection: A retrospective study. World J Gastrointest Oncol 2024; 16:1869-1877. [PMID: 38764842 PMCID: PMC11099430 DOI: 10.4251/wjgo.v16.i5.1869] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/14/2024] [Accepted: 03/28/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Paradoxically, patients with T4N0M0 (stage II, no lymph node metastasis) colon cancer have a worse prognosis than those with T2N1-2M0 (stage III). However, no previous report has addressed this issue. AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients. METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021, of which 112 patients were assigned to the training cohort, and the remaining 88 patients were assigned to the validation cohort. Differences between the training and validation groups were analyzed. The training cohort was subjected to multivariate analysis to select prognostic risk factors for T4N0M0 colon cancer, followed by the construction of a nomogram model. RESULTS The 3-year overall survival (OS) rates were 86.2% and 74.4% for the training and validation cohorts, respectively. Enterostomy (P = 0.000), T stage (P = 0.001), right hemicolon (P = 0.025), irregular review (P = 0.040), and carbohydrate antigen 199 (CA199) (P = 0.011) were independent risk factors of OS in patients with T4N0M0 colon cancer. A nomogram model with good concordance and accuracy was constructed. CONCLUSION Enterostomy, T stage, right hemicolon, irregular review, and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer. The nomogram model exhibited good agreement and accuracy.
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Affiliation(s)
- Bang Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Zhao-Xiong Zhang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Xin-Yang Nie
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Wei-Lin Sun
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Yong-Jia Yan
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
| | - Wei-Hua Fu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China
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Khaled YS, Khot MI, Aiyappa-Maudsley R, Maisey T, Pramanik A, Tiernan J, Lintern N, Al-Enezi E, Shamsuddin SH, Tomlinson D, Coletta L, Millner PA, Hughes TA, Jayne DG. Photoactive imaging and therapy for colorectal cancer using a CEA-Affimer conjugated Foslip nanoparticle. NANOSCALE 2024; 16:7185-7199. [PMID: 38506227 PMCID: PMC10993305 DOI: 10.1039/d3nr04118b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 10/08/2023] [Indexed: 03/21/2024]
Abstract
Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.
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Affiliation(s)
- Yazan S Khaled
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | - M Ibrahim Khot
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | | | - Thomas Maisey
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | - Arindam Pramanik
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | - Jim Tiernan
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | - Nicole Lintern
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Eiman Al-Enezi
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Shazana H Shamsuddin
- Department of Pathology, School of Medical Sciences, University Sains Malaysia, Malaysia
| | - Darren Tomlinson
- School of Molecular and Cellular Biology, University of Leeds, Leeds, UK
| | - Louise Coletta
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
| | - Paul A Millner
- School of Biomedical Sciences, University of Leeds, Leeds, UK
| | - Thomas A Hughes
- School of Medicine, University of Leeds, Leeds, UK
- School of Science, Technology and Health, York St John University, York, UK
| | - David G Jayne
- Leeds Institute of Medical Research, St James's University Hospital, Leeds, United Kingdom.
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Lindmark G, Olsson L, Sitohy B, Israelsson A, Blomqvist J, Kero S, Roshdy T, Söderholm M, Turi A, Isaksson J, Sakari T, Dooper M, Dafnis G, Forsberg P, Skovsted S, Walldén M, Kung CH, Rutegård M, Nordmyr J, Muhrbeck M, Hammarström S, Hammarström ML. qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis. Int J Cancer 2024; 154:573-584. [PMID: 37700602 DOI: 10.1002/ijc.34718] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/01/2023] [Accepted: 08/14/2023] [Indexed: 09/14/2023]
Abstract
One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.
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Affiliation(s)
- Gudrun Lindmark
- Department of Clinical Sciences, Lund University, Helsingborg, Sweden
- Specialistläkarna, Malmö, Sweden
| | | | - Basel Sitohy
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Anne Israelsson
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
| | | | | | - Tamer Roshdy
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
- Department of Molecular Biology, Genetic Engineering, and Biotechnology Research Institute, University of Sadat City, Sadat City, Menoufia, Egypt
| | | | - Annamaria Turi
- Department of Clinical Pathology and Cytology, Blekinge Hospital, Karlskrona, Sweden
| | - Jessica Isaksson
- Department of Clinical Pathology and Cytology, Blekinge Hospital, Karlskrona, Sweden
| | - Thorbjörn Sakari
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
- Department of Surgery, Gävle Hospital, Gävle, Sweden
| | - Michiel Dooper
- Department of Clinical Pathology and Cytology, Gävle Hospital, Gävle, Sweden
| | - George Dafnis
- Colorectal Unit, Department of Surgery and Urology, Mälarsjukhuset, Eskilstuna, Sweden
| | - Pehr Forsberg
- Unilabs, Clinical Pathology and Cytology, Mälarsjukhuset, Eskilstuna, Sweden
| | | | - Maria Walldén
- Centrum for Surgery, Sundsvall Hospital, Sundsvall, Sweden
| | - Chih-Han Kung
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden
- Department of Surgery, Skellefteå Hospital, Skellefteå, Sweden
| | - Martin Rutegård
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Johanna Nordmyr
- Department of Clinical Pathology, Linköping University Hospital, Linköping, Sweden
| | - Måns Muhrbeck
- Department of Surgery in Norrköping, Linköping University, Norrköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Sten Hammarström
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
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Saez de Gordoa K, Rodrigo-Calvo MT, Archilla I, Lopez-Prades S, Diaz A, Tarragona J, Machado I, Ruiz Martín J, Zaffalon D, Daca-Alvarez M, Pellisé M, Camps J, Cuatrecasas M. Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study. Cancers (Basel) 2023; 15:5481. [PMID: 38001742 PMCID: PMC10670609 DOI: 10.3390/cancers15225481] [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: 10/13/2023] [Revised: 11/11/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.
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Affiliation(s)
- Karmele Saez de Gordoa
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Maria Teresa Rodrigo-Calvo
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Ivan Archilla
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Sandra Lopez-Prades
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
| | - Alba Diaz
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
| | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, 25198 Lleida, Spain;
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncología, Hospital Quirón-Salud Valencia, University of Valencia, 46010 Valencia, Spain;
- Centro de Investigación Biomédica en Red en Cancer (CIBERONC), 28029 Madrid, Spain
| | - Juan Ruiz Martín
- Pathology Department, Virgen de la Salud Hospital, 45071 Toledo, Spain;
| | - Diana Zaffalon
- Gastroenterology Department, Consorci Sanitari de Terrassa, 08227 Terrassa, Spain;
| | - Maria Daca-Alvarez
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Maria Pellisé
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain;
| | - Jordi Camps
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Cell Biology and Medical Genetics Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Autonomous University of Barcelona (UAB), 08193 Bellaterra, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain; (K.S.d.G.); (M.T.R.-C.); (I.A.); (S.L.-P.); (A.D.)
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; (M.P.); (J.C.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Clinical Foundations, University of Barcelona (UB), 08036 Barcelona, Spain
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7
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Kuvaldina AB, Buote N, Campoy L, Porter I, Hayes GM. Development of a minimally invasive endoscopic technique for excisional biopsy of the axillary lymph nodes in dogs. Vet Surg 2023; 52:888-896. [PMID: 36281637 DOI: 10.1111/vsu.13901] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 07/31/2022] [Accepted: 09/01/2022] [Indexed: 08/19/2023]
Abstract
OBJECTIVE To develop and describe a minimally invasive technique for excisional biopsy of the axillary lymph nodes in dogs. STUDY DESIGN Descriptive cadaver and clinical case series. ANIMALS Four canine cadavers and three clinical patients. METHODS A 3D computed tomographic reconstruction of the canine axilla was used to identify an optimal avenue of approach to the lymph nodes. This approach was refined using endoscopic techniques in four cadavers (six procedures) and potential surgical hazards, landmarks, and the surgical time required for excisional biopsy of the nodes was recorded. The procedure was then performed in three clinical cases. RESULTS Axillary lymph node removal was achieved using an endoscopic technique with surgical times of 58 and 35 minutes in two of three clinical cases. The third case required conversion to an open approach after endoscopic identification of the node. No major complications were encountered. CONCLUSION Excisional biopsy of the axillary lymph nodes can be performed successfully using a minimally invasive technique in the dog. Further investigation in clinical cases is needed to determine the risks and complications of this procedure. CLINICAL SIGNIFICANCE Minimally invasive excisional biopsy of the axillary lymph nodes in dogs can be performed and may have a role in assisting with staging and local disease control in oncologic cases.
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Affiliation(s)
| | - Nicole Buote
- Cornell University College of Veterinary Medicine, Ithaca, New York, USA
| | - Luis Campoy
- Cornell University College of Veterinary Medicine, Ithaca, New York, USA
| | - Ian Porter
- Cornell University College of Veterinary Medicine, Ithaca, New York, USA
| | - Galina M Hayes
- Cornell University College of Veterinary Medicine, Ithaca, New York, USA
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8
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Krogue JD, Azizi S, Tan F, Flament-Auvigne I, Brown T, Plass M, Reihs R, Müller H, Zatloukal K, Richeson P, Corrado GS, Peng LH, Mermel CH, Liu Y, Chen PHC, Gombar S, Montine T, Shen J, Steiner DF, Wulczyn E. Predicting lymph node metastasis from primary tumor histology and clinicopathologic factors in colorectal cancer using deep learning. COMMUNICATIONS MEDICINE 2023; 3:59. [PMID: 37095223 PMCID: PMC10125969 DOI: 10.1038/s43856-023-00282-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 03/29/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Presence of lymph node metastasis (LNM) influences prognosis and clinical decision-making in colorectal cancer. However, detection of LNM is variable and depends on a number of external factors. Deep learning has shown success in computational pathology, but has struggled to boost performance when combined with known predictors. METHODS Machine-learned features are created by clustering deep learning embeddings of small patches of tumor in colorectal cancer via k-means, and then selecting the top clusters that add predictive value to a logistic regression model when combined with known baseline clinicopathological variables. We then analyze performance of logistic regression models trained with and without these machine-learned features in combination with the baseline variables. RESULTS The machine-learned extracted features provide independent signal for the presence of LNM (AUROC: 0.638, 95% CI: [0.590, 0.683]). Furthermore, the machine-learned features add predictive value to the set of 6 clinicopathologic variables in an external validation set (likelihood ratio test, p < 0.00032; AUROC: 0.740, 95% CI: [0.701, 0.780]). A model incorporating these features can also further risk-stratify patients with and without identified metastasis (p < 0.001 for both stage II and stage III). CONCLUSION This work demonstrates an effective approach to combine deep learning with established clinicopathologic factors in order to identify independently informative features associated with LNM. Further work building on these specific results may have important impact in prognostication and therapeutic decision making for LNM. Additionally, this general computational approach may prove useful in other contexts.
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Affiliation(s)
| | | | - Fraser Tan
- Google Health, Palo Alto, California, USA
| | | | | | | | | | | | | | - Pema Richeson
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | | | | | | | - Yun Liu
- Google Health, Palo Alto, California, USA
| | | | - Saurabh Gombar
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Thomas Montine
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
| | - Jeanne Shen
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
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9
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Rodrigo-Calvo MT, Saez de Gordoa K, Lopez-Prades S, Archilla I, Diaz A, Berrios M, Camps J, Musulen E, Cuatrecasas M. Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer. Cancers (Basel) 2023; 15:cancers15030842. [PMID: 36765800 PMCID: PMC9913321 DOI: 10.3390/cancers15030842] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/01/2023] Open
Abstract
Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient's clinical management.
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Affiliation(s)
- Maria Teresa Rodrigo-Calvo
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Karmele Saez de Gordoa
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Sandra Lopez-Prades
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Ivan Archilla
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Alba Diaz
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Basic Clinical Practice, University of Barcelona (UB), 08036 Barcelona, Spain
| | - Mario Berrios
- Pathology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
| | - Jordi Camps
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Gastroenterology Department, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain
- Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University Autonomous of Barcelona, 08193 Bellaterra, Spain
| | - Eva Musulen
- Pathology Department, Hospital Universitari General de Catalunya-Grupo QuironSalud, Sant Cugat del Vallès, 08195 Barcelona, Spain
- Josep Carreras Leukaemia Research Institute, Badalona, 08916 Barcelona, Spain
- Correspondence: (E.M.); (M.C.); Tel.: +34-935047940 (E.M.); +34-932275536 (M.C.)
| | - Miriam Cuatrecasas
- Pathology Department, Centre of Biomedical Diagnosis (CDB), Hospital Clinic, 08036 Barcelona, Spain
- Molecular Pathology of Inflammatory Conditions and Solid Tumours Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), 28029 Madrid, Spain
- Department of Basic Clinical Practice, University of Barcelona (UB), 08036 Barcelona, Spain
- Correspondence: (E.M.); (M.C.); Tel.: +34-935047940 (E.M.); +34-932275536 (M.C.)
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10
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Cytology Smears: An Enhanced Alternative Method for Colorectal Cancer pN Stage-A Multicentre Study. Cancers (Basel) 2022; 14:cancers14246072. [PMID: 36551559 PMCID: PMC9775901 DOI: 10.3390/cancers14246072] [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: 11/01/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and H&E. Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients.
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11
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Liu PL, Wang DD, Pang CJ, Zhang LZ. Impact of adequate lymph nodes dissection on survival in patients with stage I rectal cancer. Front Oncol 2022; 12:985324. [DOI: 10.3389/fonc.2022.985324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 10/28/2022] [Indexed: 11/21/2022] Open
Abstract
Background and AimsThe NCCN guidelines recommended an assessment of ≥ 12 lymph nodes (LN) as an adequate LN dissection (LND) for rectal cancer (RC). However, the impact of adequate LND on survival in stage I RC patients remained unclear. Thus, we aimed to compare the survival between stage I RC patients with adequate and inadequate LND.MethodsA total of 1,778 stage I RC patients in the SEER database from 2010 to 2017 treated with radical proctectomy were identified. The association between ≥ 12 LND and survival was examined using the multivariate Cox regression and the multivariate competing risk model referenced to < 12 LND.ResultsStage I RC patients with ≥ 12 LND experienced a significantly lower hazard of cancer-specific death compared with those with < 12 LND in both multivariate Cox regression model (adjusted HR [hazard ratio], 0.44, 95% CI, 0.29-0.66; P < 0.001) and the multivariate competing risk model (adjusted subdistribution HR [SHR], 0.45, 95% CI, 0.30-0.69; P < 0.001). Further, subgroup analyses performed by pT stage. No positive association between ≥ 12 LND and survival was found in pT1N0 RC patients (adjusted HR: 0.62, 95%CI, 0.32-1.19; P = 0.149; adjusted SHR: 0.63, 95%CI, 0.33-1.20; P = 0.158), whereas a positive association between ≥ 12 LND and survival was found in pT2N0 RC patients (adjusted HR: 0.35, 95%CI, 0.21-0.58; P < 0.001; adjusted SHR: 0.36, 95%CI, 0.21-0.62; P < 0.001).ConclusionsThe long-term survival benefit of adequate LND was not found in pT1N0 but in pT2N0 RC patients, which suggested that pT2N0 RC patients should be treated with adequate LND and those with inadequate LND might need additional therapy.
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12
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Giani A, Bertoglio CL, Mazzola M, Giusti I, Achilli P, Carnevali P, Origi M, Magistro C, Ferrari G. Mid-term oncological outcomes after complete versus conventional mesocolic excision for right-sided colon cancer: a propensity score matching analysis. Surg Endosc 2022; 36:6489-6496. [PMID: 35028735 DOI: 10.1007/s00464-021-09001-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/31/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The correct extent of mesocolic dissection for right-sided colon cancer (RCC) is still under debate. Complete mesocolic excision (CME) has not gained wide diffusion, mainly due to its technical complexity and unclear oncological superiority. This study aims to evaluate oncological outcomes of CME compared with non-complete mesocolic excision (NCME) during resection for I-III stage RCC. METHOD Prospectively collected data of patients who underwent surgery between 2010 and 2018 were retrospectively analysed. 1:1 Propensity score matching (PSM) was used to balance baseline characteristics of CME and NCME patients. The primary endpoint of the study was local recurrence-free survival (LRFS). The two groups were also compared in terms of short-term outcomes, distant recurrence-free survival, disease-free survival, and overall survival. RESULTS Of the 444 patients included in the study, 292 were correctly matched after PSM, 146 in each group. The median follow-up was 45 months (IQR 33-63). Conversion rate, complications, and 90-day mortality were comparable in both groups. The median number of lymph nodes harvested was higher in CME patients (23 vs 19, p = 0.034). 3-year LRFS rates for CME patients was 100% and 95.6% for NCME (log-rank p = 0.028). At 3 years, there were no differences between the groups in terms of overall survival, distant recurrence-free survival, and disease-free survival. CONCLUSION Our PSM cohort study shows that CME is safe, provides a higher number of lymph nodes harvested, and is associated with better local recurrence-free survival.
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Affiliation(s)
- Alessandro Giani
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy.
| | - Camillo Leonardo Bertoglio
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Michele Mazzola
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Irene Giusti
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Pietro Achilli
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Pietro Carnevali
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Matteo Origi
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Carmelo Magistro
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
| | - Giovanni Ferrari
- Division of Minimally-Invasive Surgical Oncology, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore, 3, 20162, Milan, Italy
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13
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Crafa F, Vanella S, Catalano OA, Pomykala KL, Baiamonte M. Role of one-step nucleic acid amplification in colorectal cancer lymph node metastases detection. World J Gastroenterol 2022; 28:4019-4043. [PMID: 36157105 PMCID: PMC9403438 DOI: 10.3748/wjg.v28.i30.4019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 06/03/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
Current histopathological staging procedures in colorectal cancer (CRC) depend on midline division of the lymph nodes (LNs) with one section of hematoxylin and eosin staining. Cancer cells outside this transection line may be missed, which could lead to understaging of Union for International Cancer Control Stage II high-risk patients. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid molecular diagnostic tool for LN metastases detection. It is a molecular technique that can analyze the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumor-specific cytokeratin 19 mRNA. Our findings suggest that the OSNA assay has a high diagnostic accuracy in detecting metastatic LNs in CRC and a high negative predictive value. OSNA is a standardized, observer-independent technique, which may lead to more accurate staging. It has been suggested that in stage II CRC, the upstaging can reach 25% and these patients can access postoperative adjuvant chemotherapy. Moreover, intraoperative OSNA sentinel node evaluation may allow early CRC to be treated with organ-preserving surgery, while in more advanced-stage disease, a tailored lymphadenectomy can be performed considering the presence of aberrant lymphatic drainage and skip metastases.
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Affiliation(s)
- Francesco Crafa
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Serafino Vanella
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
| | - Onofrio A Catalano
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Kelsey L Pomykala
- Department of Nuclear Medicine, Department of Radiological Sciences, David Geffen School of Medicine at University of California, Los Angeles, University Hospital Essen, University of Duisburg-Essen, Essen 45141, Germany
| | - Mario Baiamonte
- Division of General and Surgical Oncology, St. Giuseppe Moscati Hospital, Center of National Excellence and High Specialty, Avellino 83100, Italy
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14
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Kang BM, Park JS, Kim HJ, Park SY, Yoon G, Choi GS. Prognostic Value of Mesorectal Lymph Node Micrometastases in ypN0 Rectal Cancer After Chemoradiation. J Surg Res 2022; 276:314-322. [DOI: 10.1016/j.jss.2022.02.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 02/11/2022] [Accepted: 02/17/2022] [Indexed: 11/24/2022]
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Yamamoto H. Micrometastasis in lymph nodes of colorectal cancer. Ann Gastroenterol Surg 2022; 6:466-473. [PMID: 35847437 PMCID: PMC9271024 DOI: 10.1002/ags3.12576] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 04/21/2022] [Indexed: 11/11/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. Postoperative adjuvant chemotherapy is recommended for node-positive stage III patients. A systematic meta-analysis reported that the presence of micrometastases in regional lymph nodes (LNs) was associated with poor survival in patients with node-negative CRC. Because most data employed in the meta-analysis were based on retrospective studies, we conducted a prospective clinical trial and concluded that stage II is a transitional zone between stage I and stage III, where CRC tumors continuously increase the micrometastasis volume in LNs and proportionally raise the risk for tumor recurrence. The one-step nucleic acid amplification (OSNA) assay is a simple and rapid technique to detect CK19 mRNA using the reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method. Using the OSNA assay, we and colleagues reported that the upstaging rates of pStages I, IIA, IIB, and IIC were 2.0%, 17.7%, 12.5%, and 25%, respectively, in 124 node-negative patients. Survival analysis indicated that OSNA positive stage II CRC patients had a shorter 3-y disease-free survival rate than OSNA negative stage II CRC patients. In 2017, AJCC TNM staging (the 8th version) revised the definition of LN metastasis in colon cancer and it is stated that micrometastasis should be considered as a standard LN metastasis. To our surprise, this revision was based on a meta-analysis to which our previous study on micrometastasis largely contributed. The remaining questions to be addressed are how to find micrometastases efficiently and whether postadjuvant chemotherapy is effective to prevent disease recurrence and to contribute to longer survival.
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Affiliation(s)
- Hirofumi Yamamoto
- Department of Surgery, Gastroenterological Surgery, Graduate School of MedicineOsaka UniversityOsakaJapan
- Department of Molecular Pathology, Division of Health Sciences, Graduate School of MedicineOsaka UniversityOsakaJapan
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16
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Vogel JD, Felder SI, Bhama AR, Hawkins AT, Langenfeld SJ, Shaffer VO, Thorsen AJ, Weiser MR, Chang GJ, Lightner AL, Feingold DL, Paquette IM. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colon Cancer. Dis Colon Rectum 2022; 65:148-177. [PMID: 34775402 DOI: 10.1097/dcr.0000000000002323] [Citation(s) in RCA: 176] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
| | | | | | | | | | | | - Amy J Thorsen
- Colon and Rectal Surgery Associates, Minneapolis, Minnesota
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Struys MJ, Ceelen WP. Anatomical and temporal patterns of lymph node metastasis in colorectal cancer. THE LYMPHATIC SYSTEM IN COLORECTAL CANCER 2022:131-151. [DOI: 10.1016/b978-0-12-824297-1.00001-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Saha S, Philimon B, Efeson M, Helina A, Elgamal M, Kiya G, Hilkiah S, Arora M, Wiese D, Kitagawa Y. The role of sentinel lymph node mapping in colon cancer: detection of micro-metastasis, effect on survival, and driver of a paradigm shift in extent of colon resection. Clin Exp Metastasis 2021; 39:109-115. [PMID: 34698993 DOI: 10.1007/s10585-021-10121-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 08/30/2021] [Indexed: 11/28/2022]
Abstract
Unlike in breast cancer and melanoma, sentinel lymph node mapping in colon cancer is primarily used as an aid to the pathologist for accurate nodal staging. The study was undertaken to review the incidence of micro-metastasis and its impact on survival when treated with chemotherapy. The study was also undertaken to see if SLNM could guide limited colon resection in early T stage tumor as a paradigm shift. SLNM was done by subserosal injection of a blue dye. SLNs were ultra-staged by multilevel sectioning and remaining Specimen was then examined by conventional method. For the last 245 patients the specimen was divied ex vivo into two segments as segment A containing the tumor bearing portion of the colon and SLNs with attached mesentery, while segment B include distal part of the colon with attached mesentery. Nodal staging was separately examined. Of the 354 Pts, SLNM was successful in 99.9% of Pts with an average no of SLN/ Pt = 2.8 and total nodes 17.8/pt. Survival was directly related negatively with stage and nodal status. Pts with +ve LN did much better with chemotherapy than without chemotherapy. With 245 Pts, specimen A Vs B, no Pts had +ve node in specimen B with -ve LN in specimen A. SLNM results in more node/Pt, more positive node/Pt ,and more micro-metastasis who when treated with chemotherapy survive longer. Limited segmental resection in early T stage is possible when done with guidance by SLNM without compromising biology.
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Affiliation(s)
- Sukamal Saha
- McLaren Regional Medical Center, Flint, MI, USA.
| | - Bekele Philimon
- Myungsung Christian Medical Center (MCM), Addis Ababa, Ethiopia
| | - Malore Efeson
- Myungsung Christian Medical Center (MCM), Addis Ababa, Ethiopia
| | - Abebe Helina
- Myungsung Christian Medical Center (MCM), Addis Ababa, Ethiopia
| | | | - Gurmessa Kiya
- Myungsung Christian Medical Center (MCM), Addis Ababa, Ethiopia
| | - Suga Hilkiah
- Myungsung Christian Medical Center (MCM), Addis Ababa, Ethiopia
| | - Madan Arora
- McLaren Regional Medical Center, Flint, MI, USA
| | - David Wiese
- McLaren Regional Medical Center, Flint, MI, USA
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Clinical Significance of Lymph Node Micrometastasis in pN0 Gastric Cancer Patients. Gastroenterol Res Pract 2021; 2021:6854646. [PMID: 33747076 PMCID: PMC7946449 DOI: 10.1155/2021/6854646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 02/11/2021] [Accepted: 02/23/2021] [Indexed: 02/06/2023] Open
Abstract
Purpose To investigate the relationship between lymph node micrometastasis (LNMM) and clinicopathological factors and to evaluate the prognostic effects of LNMM in pN0 gastric cancer (GC) patients. Methods One hundred and seventy-two GC patients who received radical gastrectomy with D2 lymph node dissection were enrolled in the present study. 1371 negative lymph nodes from level 2 station confirmed by pathology were examined. The LNMM was diagnosed by telomeric repeat amplification protocol/enzyme-linked immunosorbent assay (TRAP-ELISA). The relationship between clinicopathological factors and LNMM was investigated by multivariate analysis. Survival analysis was performed to evaluate the effects of LNMM on prognosis. Results LNMM was detected in 423 lymph nodes from 72 patients. The results showed that invasion depth (OR = 3.755, P = 0.004), TNM staging (OR = 3.152, P = 0.002), lymphatic invasion (OR = 2.178, P = 0.009), and tumor differentiation (OR = 1.266, P = 0.013) were independent risk factors associated with LNMM. Survival analysis showed that patients with LNMM had significantly worse 5-year survival compared with those without LNMM (42% vs. 76.4%, P < 0.05). Multivariate analysis demonstrated that LNMM, tumor size, Lauren type, invasion depth, and lymphatic invasion (P < 0.05) were independently factors associated with 5-year survival. Conclusions The findings showed that tumor invasion depth, TNM staging, lymphatic invasion, and tumor differentiation were independent risk factors associated with LNMM occurrence. Moreover, LNMM is a clinically negative prognostic factor in pN0 GC patients.
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Archilla I, Díaz-Mercedes S, Aguirre JJ, Tarragona J, Machado I, Rodrigo MT, Lopez-Prades S, Gorostiaga I, Landolfi S, Alén BO, Balaguer F, Castells A, Camps J, Cuatrecasas M. Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma? Clin Transl Gastroenterol 2021; 12:e00303. [PMID: 33939382 PMCID: PMC7909319 DOI: 10.14309/ctg.0000000000000303] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 12/18/2020] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC. METHODS In this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry. RESULTS One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001). DISCUSSION The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).
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Affiliation(s)
- Ivan Archilla
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Sherley Díaz-Mercedes
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | | | - Jordi Tarragona
- Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain
| | - Isidro Machado
- Pathology Department, Instituto Valenciano de Oncologia and Hospital QuironSalud, Valencia, Spain
| | - Maria Teresa Rodrigo
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Sandra Lopez-Prades
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
| | - Iñigo Gorostiaga
- Pathology Department, Arava University Hospital, Vitoria-Gasteiz, Spain
| | - Stefania Landolfi
- Pathology Department, Vall Hebron University Hospital, Barcelona, Spain
| | - Begoña Otero Alén
- Molecular Pathology Division, Pathology Department, CHUAC/INIBIC, A Coruña, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Jordi Camps
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
| | - Miriam Cuatrecasas
- Pathology Department, Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, IDIBAPS, Spain
- Centro de Investigación Biomédica en Red. Enfermedades Hepáticas y Digestivas (CIBERehd). ISCiii. Spain
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21
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Abstract
Well executed multicenter clinical trials often provide significant evidence and support for, or against, foundational aspects of clinical procedures perceived to improve clinical management of a medical condition. In this review, discussed are reports of multicenter clinical trials designed to investigate sentinel lymph node biopsy procedures in seven types of cancer: breast, melanoma, head and neck, gastric, colon, uterine, and vulvar-with focus on the most recent reports of the hypotheses, objectives, parameters, data, results, implications, and impacts of the included trials. Such trials generally enroll more subjects, in shorter time periods, than do single-center studies. Such studies generally also have greater diversities among investigator practitioners and investigative environments than do single-center studies. The greater number of subjects provides more power to statistical analyses performed in such studies. The more rapid accrual usually results in data being more consistently acquired. The diversities of practitioners and environments may produce results that are more conservative than might be obtained from more "focused" studies; however, diversities in a study often identify implicitly results that are more robust-that is results applicable by more practitioners and applicable in more environments.
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Affiliation(s)
- Valeria M Moncayo
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA
| | - Erin E Grady
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA
| | - Naomi P Alazraki
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA; Nuclear Medicine Service, Atlanta Veterans Affairs Healthcare System, Decatur, GA
| | - John N Aarsvold
- Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA; Nuclear Medicine Service, Atlanta Veterans Affairs Healthcare System, Decatur, GA.
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22
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Flickinger JC, Rappaport JA, Barton JR, Baybutt TR, Pattison AM, Snook AE, Waldman SA. Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies. Biomark Med 2021; 15:201-217. [PMID: 33470843 PMCID: PMC8293028 DOI: 10.2217/bmm-2020-0359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal cancers encompass a diverse class of tumors arising in the GI tract, including esophagus, stomach, pancreas and colorectum. Collectively, gastrointestinal cancers compose a high fraction of all cancer deaths, highlighting an unmet need for novel and effective therapies. In this context, the transmembrane receptor guanylyl cyclase C (GUCY2C) has emerged as an attractive target for the prevention, detection and treatment of many gastrointestinal tumors. GUCY2C is an intestinally-restricted protein implicated in tumorigenesis that is universally expressed by primary and metastatic colorectal tumors as well as ectopically expressed by esophageal, gastric and pancreatic cancers. This review summarizes the current state of GUCY2C-targeted modalities in the management of gastrointestinal malignancies, with special focus on colorectal cancer, the most incident gastrointestinal malignancy.
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Affiliation(s)
- John C Flickinger
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Jeffrey A Rappaport
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Joshua R Barton
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Trevor R Baybutt
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Amanda M Pattison
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Adam E Snook
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Scott A Waldman
- Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA
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23
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Hiyoshi Y, Akiyoshi T, Fukunaga Y. The advantage of one-step nucleic acid amplification for the diagnosis of lymph node metastasis in colorectal cancer patients. Ann Gastroenterol Surg 2021; 5:60-66. [PMID: 33532681 PMCID: PMC7832960 DOI: 10.1002/ags3.12392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/28/2020] [Accepted: 08/01/2020] [Indexed: 12/20/2022] Open
Abstract
Generally, the postoperative examination of lymph nodes (LNs) is based on a microscopic examination of one hematoxylin and eosin (HE)-stained slide; however, an examination of only one part of the LN might lead to incorrect staging of the tumor due to tissue allocation bias. Although multilevel sectioning and the use of immunohistochemistry (IHC) have improved the detection of micrometastases in LNs, this approach is laborious, time-consuming, and costly. A novel molecular technique for the detection of LN metastases of tumors, called one-step nucleic acid amplification (OSNA), is a rapid and semi-quantitative examination quantifying the number of cytokeratin 19 (CK-19) mRNA copies derived from a tumor. OSNA is already in clinical use for the diagnosis of LN metastasis in breast cancer patients; however, the use of OSNA is under investigation with promising results for colorectal cancer (CRC). The present review assessed recent studies on OSNA vs a histopathological examination and its implications for CRC staging and treatment. A total of 16 studies of OSNA in CRC yielded by a PubMed search were reviewed. Among them, seven studies evaluating the diagnostic performance revealed that OSNA had a high specificity (96.8%), high concordance rate (96.0%), and negative predictive value (98.6%) in a pooled assessment. In addition, four studies examining the utility of OSNA in sentinel LNs (SLNs) and two studies focusing on upstaging in pathologically node-negative CRC patients were also reviewed. Multicenter prospective studies with a large cohort of CRC patients are warranted to reveal the benefits of OSNA in the future.
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Affiliation(s)
- Yukiharu Hiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Takashi Akiyoshi
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
| | - Yosuke Fukunaga
- Gastroenterological CenterDepartment of Gastroenterological SurgeryThe Cancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
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24
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Navarro S, Cuatrecasas M, Hernández-Losa J, Landolfi S, Musulén E, Ramón Y Cajal S, García-Carbonero R, García-Foncillas J, Pérez-Segura P, Salazar R, Vera R, García-Alfonso P. [Update of the recommendations for the determination of biomarkers in colorectal carcinoma. National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology]. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2020; 54:41-54. [PMID: 33455693 DOI: 10.1016/j.patol.2020.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/02/2020] [Accepted: 07/26/2020] [Indexed: 11/25/2022]
Abstract
This update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP), reviews the advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the possible benefits of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From a pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide which, like the previous one, will be revised when necessary in the future.
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Affiliation(s)
- Samuel Navarro
- Departamento de Patología, Universidad de Valencia, Hospital Clínico Universitario de Valencia, CIBERONC, Valencia, España.
| | | | - Javier Hernández-Losa
- Departamento de Patología, Hospital Universitario Vall d'Hebron, CIBERONC, Barcelona, España
| | - Stefania Landolfi
- Departamento de Patología, Hospital Universitario Vall d'Hebron, CIBERONC, Barcelona, España
| | - Eva Musulén
- Departamento de Patología, Hospital Universitari General de Catalunya, Grupo Quirónsalud, Sant Cugat del Vallès, España; Grupo de Epigenética del Cáncer, Institut de Recerca contra la Leucèmia Josep Carreras, Badalona, España
| | - Santiago Ramón Y Cajal
- Departamento de Patología, Hospital Universitario Vall d'Hebron, CIBERONC, Barcelona, España
| | - Rocío García-Carbonero
- Departamento de Oncología Médica, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, España
| | - Jesús García-Foncillas
- Departamento de Oncología, Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, España
| | - Pedro Pérez-Segura
- Departamento de Oncología Médica, Hospital Clínico Universitario San Carlos, CIBERONC, Madrid, España
| | - Ramón Salazar
- Departamento de Oncología Médica, ICO ĹHospitalet, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, España
| | - Ruth Vera
- Departamento de Oncología Médica, Complejo Hospitalario de Navarra, Navarrabiomed, IDISNA, Pamplona, España
| | - Pilar García-Alfonso
- Departamento de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, España
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25
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Rappaport JA, Waldman SA. An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer. Expert Rev Clin Pharmacol 2020; 13:1125-1137. [PMID: 32945718 DOI: 10.1080/17512433.2020.1826304] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Colorectal cancer remains the second leading cause of cancer death in the United States, underscoring the need for novel therapies. Despite the successes of new targeted agents for other cancers, colorectal cancer suffers from a relative scarcity of actionable biomarkers. In this context, the intestinal receptor, guanylyl cyclase C (GUCY2C), has emerged as a promising target.Areas covered: GUCY2C regulates a tumor-suppressive signaling axis that is silenced through loss of its endogenous ligands at the earliest stages of tumorigenesis. A body of literature supports a cancer chemoprevention strategy involving reactivation of GUCY2C through FDA-approved cGMP-elevating agents such as linaclotide, plecanatide, and sildenafil. Its limited expression in extra-intestinal tissues, and retention on the surface of cancer cells, also positions GUCY2C as a target for immunotherapies to treat metastatic disease, including vaccines, chimeric antigen receptor T-cells, and antibody-drug conjugates. Likewise, GUCY2C mRNA identifies metastatic cells, enhancing colorectal cancer detection, and staging. Pre-clinical and clinical programs exploring these GUCY2C-targeting strategies will be reviewed.Expert opinion: Recent mechanistic insights characterizing GUCY2C ligand loss early in tumorigenesis, coupled with results from the first clinical trials testing GUCY2C-targeting strategies, continue to elevate GUCY2C as an ideal target for prevention, detection, and therapy.
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Affiliation(s)
- Jeffrey A Rappaport
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University , Philadelphia, PA, USA
| | - Scott A Waldman
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University , Philadelphia, PA, USA
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26
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García-Alfonso P, García-Carbonero R, García-Foncillas J, Pérez-Segura P, Salazar R, Vera R, Ramón Y Cajal S, Hernández-Losa J, Landolfi S, Musulén E, Cuatrecasas M, Navarro S. Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology. Clin Transl Oncol 2020; 22:1976-1991. [PMID: 32418154 PMCID: PMC7505870 DOI: 10.1007/s12094-020-02357-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 04/28/2020] [Indexed: 12/16/2022]
Abstract
In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.
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Affiliation(s)
- P García-Alfonso
- Departament of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
| | - R García-Carbonero
- Departament of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, Spain
| | - J García-Foncillas
- Departament of Medical Oncology, Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - P Pérez-Segura
- Departament of Medical Oncology, Hospital Clínico Universitario San Carlos, CIBERONC, Madrid, Spain
| | - R Salazar
- Departament of Medical Oncology, ICO L'Hospitalet, Oncobell Program (IDIBELL), CIBERONC, Hospitalet de Llobregat, Spain
| | - R Vera
- Departament of Medical Oncology, Complejo Hospitalario de Navarra; Navarrabiomed, IDISNA, Pamplona, Spain
| | - S Ramón Y Cajal
- Department of Pathology, Hospital Universitario Vall D'Hebron, CIBERONC, Barcelona, Spain
| | - J Hernández-Losa
- Department of Pathology, Hospital Universitario Vall D'Hebron, CIBERONC, Barcelona, Spain
| | - S Landolfi
- Department of Pathology, Hospital Universitario Vall D'Hebron, CIBERONC, Barcelona, Spain
| | - E Musulén
- Department of Pathology, Hospital Universitari General de Catalunya, Grupo Quirónsalud, Sant Cugat del Vallès, Spain.,Cancer Epigenetics Group, Institut de Recerca Contra La Leucèmia Josep Carreras, Badalona, Spain
| | - M Cuatrecasas
- Department of Pathology, Hospital Clinic, CIBERehd, Barcelona, Spain
| | - S Navarro
- Department of Pathology, University of Valencia, Hospital Clínico Universitario de Valencia, CIBERONC, Valencia, Spain
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27
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Efficacy and Safety of Complete Mesocolic Excision in Patients With Colon Cancer: Three-year Results From a Prospective, Nonrandomized, Double-blind, Controlled Trial. Ann Surg 2020; 271:519-526. [PMID: 30148752 DOI: 10.1097/sla.0000000000003012] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients. SUMMARY BACKGROUND DATA CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted. METHODS Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775). RESULTS There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS. CONCLUSIONS Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.
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28
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Song W, Chen Z, Zheng Z, Hu J, Chen Y, Deng W, He X, Lan P. Prognostic value of radiologically enlarged lymph nodes in node-negative colon cancer. Colorectal Dis 2020; 22:537-543. [PMID: 31868954 DOI: 10.1111/codi.14938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 11/20/2019] [Indexed: 12/29/2022]
Abstract
AIM Assessment of lymph node (LN) involvement is of crucial importance in the estimation of prognosis and choice of therapeutic options for patients with colon cancer. The relationship between the radiological size of LNs and prognosis in node-negative colon cancer remains uncertain. This study aims to investigate the prognostic impact of radiologically enlarged LNs on the survival of patients with node-negative colon cancer. METHOD This retrospective study recruited 395 patients with Stages I and II colon cancer diagnosed between January 2012 and March 2016. Preoperative computed tomography was reviewed for the maximum short-axis diameter of regional LNs, the optimal cutoff value of which was set to 8 mm. The prognostic relevance was analysed in Kaplan-Meier and multivariable Cox proportional hazard regressions. RESULTS Patients with tumour in the left colon, TNM Stage II and 12 or more retrieved LNs tended to have radiologically enlarged LNs. Our results suggest that 3-year recurrence-free survival (RFS) and overall survival (OS) were significantly worse in patients with enlarged LNs than those without (RFS 82.8% vs 92.4%, P = 0.026; OS 87.1% vs 95.2%, P = 0.017), which was also confirmed in multivariable analysis [RFS hazard ratio (HR) = 2.192, P = 0.018; OS HR = 3.305, P = 0.010]. Subgroup analysis revealed that in patients with Stage II disease or at least 12 retrieved LNs, radiologically enlarged LN remained an independent predictor of poor RFS and OS. CONCLUSION The presence of radiologically enlarged LNs in patients with node-negative colon cancer had an adverse prognosis.
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Affiliation(s)
- W Song
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Z Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Z Zheng
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - J Hu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Y Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - W Deng
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - X He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - P Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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29
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Üreyen O, Ulusoy C, Acar A, Sağlam F, Kızıloğlu İ, Alemdar A, Atahan KM, Dadalı E, Karaisli S, Aydın MC, İlhan E, Güven H. Should there be a specific length of the colon-rectum segment to be resected for an adequate number of lymph nodes in cases of colorectal cancers? A retrospective multi-center study. Turk J Surg 2020; 36:23-32. [PMID: 32637872 PMCID: PMC7315459 DOI: 10.5578/turkjsurg.4550] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 09/05/2019] [Indexed: 11/15/2022]
Abstract
OBJECTIVES This study aimed to evaluate the question as to whether there should be a certain length of the colon-rectum segment to be resected for correct lymph node staging in cases with colorectal cancer. MATERIAL AND METHODS The files and electronic datas of the patients had been undergone surgery for colorectal cancer between January 2011 and June 2016 were evaluated. The patients were divided into two groups; Group I= ≥ 12 lymph nodes, and Group II= lymph nodes less than 12 ( <12) lymph nodes. RESULTS Mean age of the 327 participants in this study was 64.30 ± 12.20. Mean length of resected colon-rectum segment was 25.61 (± 14.07) cm; mean number of dissected lymph nodes was 20.63 ± 12.30. Median length of the resected colon was 24 cm (range: 145-6) in Group I and 20 cm (range: 52-9) in Group II; a significant difference was found between the groups (p= 0.002). Factors associated with adequate lymph node dissection included type of the operation (p= 0.001), tumor location (p= 0.005), tumor T stage (p= 0.001), condition of metastasis in the lymph node (p= 0.008) and stage of the disease (p= 0.031). Overall survival was 62.4 ± 1.31 months, and Group I and Group II survival was 61.4 ± 1.39 months and 66.7 ± 3.25 months, respectively (p= 0.449). CONCLUSION Results of the study showed that ≥ 12 lymph nodes would likely be dissected when the length of the resected colon-rectum segment is > 21 cm. We conclude that the removed colonic size can be significant when performed with oncological surgical standardization.
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Affiliation(s)
- Orhan Üreyen
- Clinic of General Surgery, Health Sciences University, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | - Cemal Ulusoy
- Clinic of General Surgery, Health Sciences University, Istanbul Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Atahan Acar
- Clinic of General Surgery, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Fazıl Sağlam
- Clinic of General Surgery, Health Sciences University, Istanbul Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - İlker Kızıloğlu
- Clinic of General Surgery, Health Sciences University, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | - Ali Alemdar
- Clinic of General Surgery, Health Sciences University, Istanbul Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Kemal Murat Atahan
- Clinic of General Surgery, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Emrah Dadalı
- Clinic of General Surgery, Health Sciences University, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | - Serkan Karaisli
- Clinic of General Surgery, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Mehmet Can Aydın
- Clinic of General Surgery, Health Sciences University, Istanbul Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Enver İlhan
- Clinic of General Surgery, Health Sciences University, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey
| | - Hakan Güven
- Clinic of General Surgery, Health Sciences University, Istanbul Okmeydani Training and Research Hospital, Istanbul, Turkey
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Itabashi M, Yamamoto H, Tomita N, Inomata M, Murata K, Hayashi S, Miyake Y, Igarashi S, Kato T, Noura S, Furuhata T, Ozawa H, Takemasa I, Yasui M, Takeyama H, Okamura S, Ohno Y, Matsuura N. Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study. Ann Surg Oncol 2019; 27:1077-1083. [PMID: 31722072 PMCID: PMC7060165 DOI: 10.1245/s10434-019-07971-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Indexed: 01/11/2023]
Abstract
Background For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. Methods We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. Results Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). Conclusions This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC. Electronic supplementary material The online version of this article (10.1245/s10434-019-07971-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Michio Itabashi
- Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku, Japan
| | - Hirofumi Yamamoto
- Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan.
| | - Naohiro Tomita
- Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, Oita, Japan
| | - Kohei Murata
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | - Shigeoki Hayashi
- Department of Digestive Surgery, Nihon University Hospital, Chiyoda, Japan
| | - Yasuhiro Miyake
- Department of Surgery, Osaka Minato Central Hospital, Osaka, Japan
| | - Seiji Igarashi
- Division of Pathology, Tsuboi Cancer Center Hospital, Koriyama, Japan
| | - Takeshi Kato
- Department of Colorectal Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Shingo Noura
- Department of Surgery, Osaka Rosai Hospital, Sakai, Japan
| | - Tomohisa Furuhata
- Division of Gastroenterological and General Surgery, St. Marianna University Toyoko Hospital, Kawasaki, Japan
| | - Heita Ozawa
- Department of Colorectal Surgery, Tochigi Cancer Center, Utsunomiya, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | | | - Shu Okamura
- Department of Surgery, Suita Municipal Hospital, Suita, Japan
| | - Yuko Ohno
- Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, Suita, Japan
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Diaz-Mercedes S, Archilla I, Camps J, de Lacy A, Gorostiaga I, Momblan D, Ibarzabal A, Maurel J, Chic N, Bombí JA, Balaguer F, Castells A, Aldecoa I, Borras JM, Cuatrecasas M. Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2019; 17:655-667. [PMID: 31115896 PMCID: PMC6748889 DOI: 10.1007/s40258-019-00482-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
BACKGROUND The presence of lymph node (LN) metastasis is a critical prognostic factor in colorectal cancer (CRC) patients and is also an indicator for adjuvant chemotherapy. The gold standard (GS) technique for LN diagnosis and staging is based on the analysis of haematoxylin and eosin (H&E)-stained slides, but its sensitivity is low. As a result, patients may not be properly diagnosed and some may have local recurrence or distant metastases after curative-intent surgery. Many of these diagnostic and treatment problems could be avoided if the one-step nucleic acid amplification assay (OSNA) was used rather than the GS technique. OSNA is a fast, automated, standardised, highly sensitive, quantitative technique for detecting LN metastases. OBJECTIVES The aim of this study was to assess the budget impact of introducing OSNA LN analysis in early-stage CRC patients in the Spanish National Health System (NHS). METHODS A budget impact analysis comparing two scenarios (GS vs. OSNA) was developed within the Spanish NHS framework over a 3-year time frame (2017-2019). The patient population consisted of newly diagnosed CRC patients undergoing surgical treatment, and the following costs were included: initial surgery, pathological diagnosis, staging, follow-up expenses, systemic treatment and surgery after recurrence. One- and two-way sensitivity analyses were performed. RESULTS Using OSNA instead of the GS would have saved €1,509,182, €6,854,501 and €10,814,082 during the first, second and third years of the analysis, respectively, because patients incur additional costs in later years, leading to savings of more than €19 million for the NHS over the 3-year time horizon. CONCLUSIONS Introducing OSNA in CRC LN analysis may represent not only an economic benefit for the NHS but also a clinical benefit for CRC patients since a more accurate staging could be performed, thus avoiding unnecessary treatments.
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Affiliation(s)
- Sherley Diaz-Mercedes
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Ivan Archilla
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Jordi Camps
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | | | - Iñigo Gorostiaga
- Pathology Department, Araba University Hospital, Vitoria-Gasteiz, Spain
| | - Dulce Momblan
- Surgical Department, Hospital Clinic, Barcelona, Spain
| | | | - Joan Maurel
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Nuria Chic
- Medical Oncology Department, Hospital Clinic of Barcelona, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Josep Antoni Bombí
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Iban Aldecoa
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain
- Neurological Tissue Bank of the Biobank Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain
| | - Josep Maria Borras
- Department of Clinical Sciences and Bellvitge Biomedical Research Institute (IDIBELL), Universitat de Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department-Center of Biomedical Diagnosis (CDB), Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain.
- Pathology Department, Araba University Hospital, Vitoria-Gasteiz, Spain.
- CIBERehd and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Hospital Clinic, Barcelona, Spain.
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Yang X, Hu T, Gu C, Yang S, Jiang D, Deng X, Wang Z, Zhou Z. The Prognostic Significance of Isolated Tumor Cells Detected Within Lateral Lymph Nodes in Rectal Cancer Patients After Laparoscopic Lateral Lymph Node Dissection. J Laparoendosc Adv Surg Tech A 2019; 29:1462-1468. [PMID: 31539301 DOI: 10.1089/lap.2019.0489] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background: To clarify the definite incidence of isolated tumor cells (ITCs) in lateral lymph nodes (LLNs) and its prognostic significance in rectal cancer patients after laparoscopic lateral lymph node dissection (lap-LLND). Methods: Consecutive rectal cancer patients who underwent standard total mesorectal excision (TME) and lap-LLND were included. All the LLNs were re-examined by hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) with a monoclonal antibody against cytokeratin 20 to confirm the status of ITCs, micrometastasis, and overt metastasis. Clinicopathological characteristics and oncological outcomes were analyzed. Results: Forty-six patients with TME and lap-LLND were included. Twelve (26.1%) patients with overt metastasis were identified. A total of 705 LLNs from 46 patients were re-examined by H&E with IHC, and ITCs were detected in 27 (3.8%) lymph nodes from 11 (23.9%) patients. No LLNs micrometastasis was found. Patients with overt metastasis had more advanced N stage and more perirectal lymph nodes metastasis. Three patients with LLNs recurrence were identified and lung metastasis was the most common metastatic site. Compared with patients with ITCs and without any metastasis, patients with overt metastasis had worse 3-year cumulative overall survival (85.7%, 83.9%, and 53.3%, respectively) and 3-year cumulative disease-free survival (85.7%, 85.2%, and 43.8%, respectively). Patients with ITCs had higher overall recurrence than patients without any metastasis (42.9% versus 11.5%, P = .035). Multivariate analysis showed that ITC status in LLNs was a significant prognostic factor (hazard ratio 2.689, 95% confidence interval 1.072-6.747; P = .035). Conclusion: ITCs in LLNs detected by the IHC method like overt metastasis detected by H&E staining contributed to higher overall recurrence.
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Affiliation(s)
- Xuyang Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chaoyang Gu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Shuo Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Jiang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Xueqin Deng
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Ziqiang Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zongguang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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Evaluation of SHP1-P2 methylation as a biomarker of lymph node metastasis in patients with squamous cell carcinoma of the head and neck. ASIAN BIOMED 2019. [DOI: 10.1515/abm-2019-0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Background
Hypermethylation of Src homology region 2 domain-containing protein-tyrosine phosphatase 1 promoter 2 (SHP1-P2) has been proven as an epithelial-specific marker. This marker has been used for the detection of lymph node metastasis in patients with lung cancer or colon cancer.
Objectives
To investigate SHP1-P2 methylation in patients with squamous cell carcinoma of the head and neck (HNSCC) and determine its potential for micrometastasis detection in the lymph nodes of patients with HNSCC.
Methods
SHP1-P2 methylation levels were analyzed by combined methylation-specific primer TaqMan real-time PCR in 5 sample groups: normal tonsils (n = 10), microdissected squamous cell carcinoma epithelia (n = 9), nonmetastatic head and neck cancer lymph nodes (LN N0, n = 15), metastatic HNSCC histologically negative for tumor cells (LN–, n = 18), and matched cases histologically positive for tumor cells (LN+, n = 18).
Results
SHP1-P2 methylation of 10.27 ± 4.05% was found in normal tonsils as a lymphoid tissue baseline, whereas it was 61.31 ± 17.00% in microdissected cancer cell controls. In the 3 lymph node groups, the SHP1-P2 methylation levels were 9.99 ± 6.61% for LN N0, 14.49 ± 10.03% for LN- Nx, and 41.01 ± 24.51% for LN+ Nx. The methylation levels for LN- Nx and LN+ Nx were significantly different (P
= 0.0002). Receiver operating characteristic curve analysis of SHP1-P2 methylation demonstrated an area under the curve of 0.637 in distinguishing LN N0 from LN– Nx.
Conclusions
SHP1-P2 methylation was high in HNSCC, and low in lymphoid tissues. This methylation difference is concordant with lymph node metastasis.
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Esposito F, Noviello A, Moles N, Coppola Bottazzi E, Baiamonte M, Macaione I, Ferbo U, Lepore M, Miro A, Crafa F. Sentinel Lymph Node Analysis in Colorectal Cancer Patients Using One-Step Nucleic Acid Amplification in Combination With Fluorescence and Indocyanine Green. Ann Coloproctol 2019; 35:174-180. [PMID: 31487764 PMCID: PMC6732328 DOI: 10.3393/ac.2018.07.21.1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 07/21/2018] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Analysis of the sentinel lymph node (SLN) in colorectal cancer (CRC) patients was proposed for more accurate staging and tailored lymphadenectomy. The aim of this study was to assess the ability to predict lymph node (LN) involvement through analysis of the SLN with a one-step nucleic acid (OSNA) technique in combination with peritumoral injection of indocyanine green (ICG) and near-infrared (NIR) lymphangiography in CRC patients. METHODS A total of 34 patients were enrolled. Overall, 51 LNs were analyzed with OSNA. LNs of 17 patients (50%) were examined simultaneously with hematoxylin and eosin (H&E) and OSNA. RESULTS SLN analysis of 17 patients examined with H&E and OSNA revealed that OSNA had a higher sensitivity (1 vs. 0.55), higher negative predictive value (1 vs. 0.66) and higher accuracy (100% vs. 76.4%) in predicting LN involvement. Overall, OSNA showed a sensitivity of 0.69, specificity of 1, accuracy of 88.2%, and stage migration of 8.8%. Compared to those who were OSNA (-), OSNA (+) patients had a greater number of LN metastases (4.8 vs. 0.16, P = 0.04), higher G3 rate (44.4% vs. 4%, P = 0.01), more advanced stage of disease (stage III: 77.8% vs. 16%; P = 0.00) and were more rapidly subjected to adjuvant chemotherapy (39.1 days vs. 50.2 days, P = 0.01). CONCLUSION SLN analysis with OSNA in combination with ICG-NIR lymphangiography is feasible and can detect LN involvement in CRC patients. Furthermore, it allows for more accurate staging reducing the delay between surgery and adjuvant chemotherapy.
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Affiliation(s)
- Francesco Esposito
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Adele Noviello
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Nicola Moles
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Enrico Coppola Bottazzi
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Mario Baiamonte
- General and Emergency Surgery Unit, Civico Benfratelli Di Cristina Hospital, Palermo, Italy
| | - Ina Macaione
- Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy
| | - Umberto Ferbo
- Institute of Pathology, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Maria Lepore
- Institute of Pathology, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Antonio Miro
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
| | - Francesco Crafa
- Oncological and General Surgery Unit, St. Giuseppe Moscati Hospital of National Relevance and High Specialty, Avellino, Italy
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Comparison of Molecular and Histologic Ultrastaging Methods in Sentinel Lymph Node Analysis from Clinical Stage II Colon Cancers. Appl Immunohistochem Mol Morphol 2019; 27:e65-e70. [PMID: 31393285 DOI: 10.1097/pai.0000000000000624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Various studies have demonstrated that occult metastases may be present in patients with clinical stage II colon cancer. The objective of this prospective investigation was to compare the performance of molecular analysis and histologic ultrastaging in detecting occult metastases in sentinel lymph nodes (SLNs). SLNs were collected ex vivo during surgery in 29 patients. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays were constructed. The results were compared with histologic ultrastaging analysis by hemalum and eosin stain and immunohistochemistry on step serial sections. At least 1 SLN was identified in 76% of the cases. The first hemalum and eosin section identified metastases in 23% of the 22 SLNs. Immunohistochemistry identified isolated tumor cells in 24% of the remaining 17 cases. An overall 73% of the SLNs analyzed by qRT-PCR were positive. Four of them were negative for ultrastaging analysis. qRT-PCR is a powerful tool for the detection of occult metastases in colorectal SLN and seems to be more sensitive than histologic ultrastaging analysis. A larger prospective cohort study is necessary to provide further evidence.
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Sun Y, Zhang Y, Huang Z, Chi P. Prognostic Implication of Negative Lymph Node Count in ypN+ Rectal Cancer after Neoadjuvant Chemoradiotherapy and Construction of a Prediction Nomogram. J Gastrointest Surg 2019; 23:1006-1014. [PMID: 30187336 DOI: 10.1007/s11605-018-3942-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 08/17/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE This study aimed to investigate the prognostic significance of negative lymph nodes (NLNs) for ypN+ rectal cancer after neoadjuvant chemoradiotherapy (nCRT) and radical surgery and to construct a nomogram predicting disease-free survival (DFS). METHOD One hundred fifty-eight eligible patients were included. X-tile analysis was performed to determine cutoff values of NLNs. Clinicopathological and survival outcomes were compared. A Cox regression analysis was performed to identify prognostic factors of DFS. A nomogram was constructed and validated internally. RESULTS X-tile analysis identified cutoff values of 4 and 16 in terms of DFS (χ2 = 8.129, p = 0.017). The 3-year DFS rates for low (≤ 4), middle (5-16), and high (≥ 17) NLNs group was 15.2, 55.5, and 73.1%, respectively (P = 0.017). NLN count (NLNs ≥ 17, HR = 0.400, P = 0.022), IMA nodal metastasis (HR = 1.944, P = 0.025), tumor differentiation (poor/anaplastic, HR = 1.805, P = 0.021), and ypT4 stage (HR = 7.787, P = 0.047) were independent prognostic factors of DFS. A predicting nomogram incorporating the four significant predictors was developed with a C-index of 0.64. CONCLUSION NLN count was an independent prognostic factor of DFS in patients with ypN+ rectal cancer following nCRT. A nomogram incorporating NLN count, IMA nodal metastasis, tumor differentiation, and ypT stage could stratify rectal cancer patients with different DFS and might be helpful during clinical decision-making.
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Affiliation(s)
- Yanwu Sun
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People's Republic of China
| | - Yiyi Zhang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People's Republic of China
| | - Zhekun Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People's Republic of China
| | - Pan Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, People's Republic of China.
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Cheng Y, Wen G, Sun Y, Shen Y, Zeng Y, Du M, Zhu G, Wang G, Meng X. Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway. Med Sci Monit 2019; 25:3014-3025. [PMID: 31017126 PMCID: PMC6496974 DOI: 10.12659/msm.913185] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 12/27/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved. MATERIAL AND METHODS Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3ß-ß/catenin pathway was detected by western blot. RESULTS OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3ß-ß/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. CONCLUSIONS OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3ß-ß/catenin pathway.
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Affiliation(s)
- Yuanguang Cheng
- Department of Gastrointestinal Surgery, The First Afliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Gang Wen
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Yong Sun
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Yang Shen
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Yongqing Zeng
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Ming Du
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Guangyu Zhu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Guanglong Wang
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
| | - Xiangling Meng
- Department of Gastrointestinal Surgery, The First Afliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China
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Numata M, Sawazaki S, Aoyama T, Tamagawa H, Sato T, Saeki H, Saigusa Y, Taguri M, Mushiake H, Oshima T, Yukawa N, Shiozawa M, Rino Y, Masuda M. D3 lymph node dissection reduces recurrence after primary resection for elderly patients with colon cancer. Int J Colorectal Dis 2019; 34:621-628. [PMID: 30659360 DOI: 10.1007/s00384-018-03233-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/29/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE The favorable oncological impact of D3 lymph node dissection after colon cancer surgery has been described previously. However, D3 lymph node dissection is potentially more invasive than conventional D2 lymph node dissection. The oncological merit of D3 lymph node dissection in elderly patients with colon cancer remains unclear. This study aimed to clarify the oncological outcome after D3 lymph node dissection in patients with colon cancer aged > 75 years. METHODS This is a retrospective cohort analysis using propensity matching method. The study was conducted at a university hospital and two community teaching hospitals in a large urban city. A total of 378 consecutive patients with pathological stage II and stage III colon cancer who underwent primary resection with either D2 or D3 lymph node dissection were retrospectively identified on a prospective database between 2000 and 2015. The primary and secondary outcomes of interests were recurrence-free survival and postoperative complication rate, respectively. RESULTS After propensity matching, 232 patients were analyzed. The long-term findings showed that the elderly who underwent D3 lymph node dissection had significantly better recurrence-free survival than those who underwent D2 lymph node dissection (p = 0.01). The incidence of postoperative complication was almost similar between the two groups. CONCLUSIONS D3 lymph node dissection provides better recurrence-free survival than D2 lymph node dissection after primary resection for elderly patients with pathological stage II and stage III colon cancer.
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Affiliation(s)
- Masakatsu Numata
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
| | - Sho Sawazaki
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Tsutomu Sato
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Hiroyuki Saeki
- Department of Surgery, Yokohama Minami Kyosai Hospital, 1-21-1 Mutsuurahigasi, Kanazawa-ku, Yokohama, Kanagawa, 236-0037, Japan
| | - Yusuke Saigusa
- Department of Biostatistics, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Masataka Taguri
- Department of Biostatistics, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Hiroyuki Mushiake
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Takashi Oshima
- Department of Gastroenterological Surgery, Kanagawa Cancer Hospital, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Manabu Shiozawa
- Department of Gastroenterological Surgery, Kanagawa Cancer Hospital, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-0815, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
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Willaert W, Cosyns S, Ceelen W. Biology-Based Surgery: The Extent of Lymphadenectomy in Cancer of the Colon. Eur Surg Res 2018; 59:371-379. [DOI: 10.1159/000494831] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 10/25/2018] [Indexed: 11/19/2022]
Abstract
The progression of colon cancer (CC) involves hematogenous and lymphatic spread to locoregional lymph nodes (LN), distant LN, and metastatic sites including the liver. The biological mechanisms that govern CC progression remain elusive. The Halsted model assumes an orderly, stepwise progression from the primary tumor to nearby nodes, henceforth to anatomically more distant nodes, and ultimately to distant organs. The Fisher model, on the other hand, regards the release of metastatic cells as early and essentially random events. The underlying biology has important implications for the ideal extent of surgery: when the Fisher model is correct, efforts to remove apical (central), extramesenteric, or para-aortic LN are unlikely to affect the oncological outcome. Recent data from phylogenetic studies suggest that cancer cell populations differ genetically among different LN stations and from distant metastases. Circulating tumor cells and other liquid biomarkers can be detected in the circulation of patients with early-stage disease. Local recurrence in CC is uncommon, and it is associated with a high risk of systemic progression and poor survival. Clinical studies comparing standard colectomy with extensive surgery (high ligation of the inferior mesenteric artery, complete mesocolic excision, D3 dissection, and para-aortic or extramesenteric node dissection) show that these techniques increase the LN count, while any beneficial effect on the risk of local recurrence or disease-free survival is at present uncertain due to the lack of controlled trials. Ongoing randomized trials comparing extensive vs. standard surgery for CC will generate important answers.
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Marks KM, West NP, Morris E, Quirke P. Clinicopathological, genomic and immunological factors in colorectal cancer prognosis. Br J Surg 2018; 105:e99-e109. [PMID: 29341159 DOI: 10.1002/bjs.10756] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 10/02/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Numerous factors affect the prognosis of colorectal cancer (CRC), many of which have long been identified, such as patient demographics and the multidisciplinary team. In more recent years, molecular and immunological biomarkers have been shown to have a significant influence on patient outcomes. Whilst some of these biomarkers still require ongoing validation, if proven to be worthwhile they may change our understanding and future management of CRC. The aim of this review was to identify the key prognosticators of CRC, including new molecular and immunological biomarkers, and outline how these might fit into the whole wider context for patients. METHODS Relevant references were identified through keyword searches of PubMed and Embase Ovid SP databases. RESULTS In recent years there have been numerous studies outlining molecular markers of prognosis in CRC. In particular, the Immunoscore® has been shown to hold strong prognostic value. Other molecular biomarkers are useful in guiding treatment decisions, such as mutation testing of genes in the epidermal growth factor receptor pathway. However, epidemiological studies continue to show that patient demographics are fundamental in predicting outcomes. CONCLUSION Current strategies for managing CRC are strongly dependent on clinicopathological staging, although molecular testing is increasingly being implemented into routine clinical practice. As immunological biomarkers are further validated, their testing may also become routine. To obtain clinically useful information from new biomarkers, it is important to implement them into a model that includes all underlying fundamental factors, as this will enable the best possible outcomes and deliver true precision medicine.
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Affiliation(s)
- K M Marks
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK
| | - N P West
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK
| | - E Morris
- Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK
| | - P Quirke
- Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK
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Clinical Impact and Prognostic Role of KRAS/BRAF/PIK3CA Mutations in Stage I Colorectal Cancer. DISEASE MARKERS 2018; 2018:2959801. [PMID: 30018674 PMCID: PMC6029483 DOI: 10.1155/2018/2959801] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/04/2018] [Accepted: 05/20/2018] [Indexed: 02/07/2023]
Abstract
Stage I colorectal carcinoma has excellent prognosis, with 5-year survival rate up to 95%. The occurrence of lymphovascular invasion, tumor budding, high number of PDC, or lymph node micrometastases is associated with tumor progression. The aim of this study was to evaluate the mutational status of 62 stage I colorectal carcinomas (CRC) (taken from 37 patients surviving more than five years since the initial diagnosis and from 25 patients who died of disease) and to correlate it with histopathological features and the clinical outcome. Mutations of KRAS, NRAS, BRAF, and PIK3CA genes were analyzed through Myriapod Colon Status Kit, using the high-throughput genotyping platform Sequenom MassARRAY System. Mutations in those genes were found in 31 cases (50%) and mainly in those with poor prognosis. The most frequent mutations occurred at codons 12 and 13 of the KRAS gene (40% of cases). We found concomitant PIK3CA mutations in 5 cases (8%). The presence of PIK3CA mutations was mainly observed in tumors with poor prognosis and with unfavorable histopathological prognostic features. High PDC grade (P = 0.0112), the presence of tumor budding (P = 0.0334), LVI (P < 0.0001), KRAS mutations (P = 0.0228), PIK3CA mutations (P = 0.0214), multiple genetic mutations in KRAS and PIK3CA genes (P = 0.039), and nodal micrometastases (P < 0.0001) were significant prognostic variables for CSS. The presence of LVI was the only independent and statistically significant prognostic variable for CSS in our cohort of pTNM stage I CRCs. The analysis of KRAS/PIK3CA mutational status may be used to identify patients with stage I CRC at high risk of bad outcome and who may need additional treatments, including biological therapies.
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Weixler B, Rickenbacher A, Raptis DA, Viehl CT, Guller U, Rueff J, Zettl A, Zuber M. Sentinel Lymph Node Mapping with Isosulfan Blue or Indocyanine Green in Colon Cancer Shows Comparable Results and Identifies Patients with Decreased Survival: A Prospective Single-Center Trial. World J Surg 2018; 41:2378-2386. [PMID: 28508233 DOI: 10.1007/s00268-017-4051-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Sentinel lymph node (SLN) mapping was reported to improve lymph node staging in colon cancer. This study compares isosulfan blue (IB) with indocyanine green (ICG)-based SLN-mapping and assesses the prognostic value of isolated tumor cells (ITC) and micro-metastases in upstaged patients. METHODS A total of 220 stage I-III colon cancer patients were included in this prospective single-center study. In 170 patients, SLN-mapping was performed in vivo with IB and in 50 patients ex vivo with ICG. Three levels of each SLN were stained with H&E. If negative for tumor infiltration, immunostaining for cytokeratin (AE1/3; cytokeratin-19) was performed. RESULTS SLN detection rate for IB and ICG was 100 and 98%, respectively. Accuracy and sensitivity was 88 and 75% for IB, 82 and 64% for ICG, respectively (p = 0.244). Overall, 149 (68%) patients were node negative. In these patients, ITC and micro-metastases were detected in 26% (31/129) with IB and 17% (5/29) with ICG (p = 0.469). Patients with ITC and micro-metastases did show decreased overall survival (hazard ratio = 1.96, p = 0.09) compared to node negative disease. CONCLUSIONS This study demonstrates a high diagnostic accuracy for both the IB and the ICG SLN-mapping. SLN-mapping upstaged a quarter of patients with node negative colon cancer, and the detected ITC and micro-metastases were an independent negative prognostic marker in multivariate analysis.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Rickenbacher
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Dimitri Aristotle Raptis
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.,Department of Visceral Surgery, University Hospital Zürich, Zurich, Switzerland
| | - Carsten T Viehl
- Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Ulrich Guller
- Division of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Jessica Rueff
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland
| | - Andreas Zettl
- Viollier AG, Histopathology/Cytology, Basel, Switzerland
| | - Markus Zuber
- Department of Surgery, Kantonsspital Olten, 4600, Olten, Switzerland.
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The Prognostic Relevance of Sentinel Lymph Node Metastases Assessed by PHGR1 mRNA Quantification in Stage I to III Colon Cancer. Transl Oncol 2018; 11:436-443. [PMID: 29475140 PMCID: PMC5884186 DOI: 10.1016/j.tranon.2018.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 01/16/2018] [Accepted: 01/16/2018] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND: Regional lymph node (LN) metastasis is a strong and well-established prognostic factor in colon cancer, and recent data suggest a prognostic value of detecting micrometastases and isolated tumor cells in regional LNs. The aim of the study was to investigate the clinical relevance of detecting sentinel lymph node (SLN) metastases in colon cancer patients by measuring the novel metastasis marker PHGR1 mRNA. METHODS: Using quantitative reverse-transcription polymerase chain reaction, we measured PHGR1 mRNA levels in SLNs and primary tumors from 206 patients surgically treated for stage I to III colon cancer and 52 normal LNs from patients undergoing surgery for benign colon diseases. The prognostic impact of these findings was evaluated by Kaplan-Meier analysis and Cox proportional-hazards regression. RESULTS: Compared to normal LNs, elevated PHGR1 mRNA levels were detected in SLNs from 56 (89%) of the 63 patients with pN+ disease. Furthermore, 68 (48%) of the 143 node-negative (pN0) patients had elevated PHGR1 mRNA levels in SLNs, suggesting occult metastases. With a median follow-up of 7.2 years, a significantly shorter recurrence-free (P=.005) and disease-specific (P=.02) survival was observed in patients with elevated PHGR1 mRNA levels in SLNs. Multivariable modeling showed that the SLN PHGR1 mRNA level was an independent prognostic factor. However, when the survival analyses were restricted to pN0 patients, no significant prognostic information was found. CONCLUSION: Measuring PHGR1 mRNA in SLNs provided independent prognostic information on operable colon cancer patients but not in the pN0 subgroup.
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Li Q, Liang L, Jia H, Li X, Xu Y, Zhu J, Cai S. Negative to positive lymph node ratio is a superior predictor than traditional lymph node status in stage III colorectal cancer. Oncotarget 2018; 7:72290-72299. [PMID: 27474167 PMCID: PMC5342162 DOI: 10.18632/oncotarget.10806] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 07/14/2016] [Indexed: 01/16/2023] Open
Abstract
Negative lymph node counts has recently attracted attention as a prognostic indicator in colorectal cancer (CRC). But little is known about prognostic significance of negative to positive lymph node ratio (NPR) in CRC. Our aim was to determine impact of NPR on oncological outcomes in patients with stage III CRC. This retrospective study included 2,256 patients with stage III CRC under curative resection at Fudan university Shanghai cancer center. Kaplan-Meier methods and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. Accuracy of the NPR was assessed with the Harrell's concordance-index(C-index).X-tile program identified 2.38 or 0.55/2.38 as the optimal cutoff value for NPR to divide the cohort into high/low risk or high/middle/low risk subsets in terms of CRC cause specific survival (CCSS). In a multivariate analysis, NPR was significant independent prognostic factors for CCSS (P<0.05), notably, N classification was not an independently prognostic factor (P>0.05). Further analysis found NPR could give detailed prognostic classification for both N1 and N2 stage (P<0.05). Interestingly, patients in N2+ NPR >2.38 stage have similar survival outcome with N1+ NPR >2.38 stage (χ2=0.030, P=0.863), and better than those at N1+ NPR ≤2.38 and N2+ NPR ≤2.38 stage (P<0.001). The TNNPRM stage was more accurate for predicting CCSS (C-index = 0.659) than current TNM stage system(C-index = 0.628) (P<0.001). Collectively, NPR was an independent prognostic factor for stage III CRC patients, it could provide more accurate prognostic information than the current node stage system.
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Affiliation(s)
- Qingguo Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Liang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Huixun Jia
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Center for Biomedical Statistics, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ji Zhu
- Center for Biomedical Statistics, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Wang H, Stoecklein NH, Lin PP, Gires O. Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion. Oncotarget 2018; 8:1884-1912. [PMID: 27683128 PMCID: PMC5352105 DOI: 10.18632/oncotarget.12242] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/20/2016] [Indexed: 12/16/2022] Open
Abstract
Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to-mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens.
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Affiliation(s)
- Hongxia Wang
- Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
| | - Nikolas H Stoecklein
- Department of General, Visceral and Pediatric Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | | | - Olivier Gires
- Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Munich, Germany.,Clinical Cooperation Group Personalized Radiotherapy of Head and Neck Tumors, Helmholtz, Germany
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46
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Wang C, Gao Z, Shen K, Shen Z, Jiang K, Liang B, Yin M, Yang X, Wang S, Ye Y. Safety, quality and effect of complete mesocolic excision vs non-complete mesocolic excision in patients with colon cancer: a systemic review and meta-analysis. Colorectal Dis 2017; 19:962-972. [PMID: 28949060 DOI: 10.1111/codi.13900] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 08/14/2017] [Indexed: 12/11/2022]
Abstract
AIM The application of complete mesocolic excision (CME) in colon cancer is controversial. We performed a meta-analysis to compare the safety, quality and effect of CME with non-complete mesocolic excision (NCME) in patients with colon cancer. METHOD We searched PubMed, ScienceDirect, the Cochrane Library and Scopus to identify studies comparing CME with NCME in colon cancer. We focused on three study outcome areas: safety (operation time, blood loss, complications, mortality); quality (large bowel length, distance from the tumour to the high vascular tie, area of mesentery, total lymph nodes); and effect (long-term survival). RESULTS A total of 8586 patients from 12 studies were included in the meta-analysis. CME was associated with greater intra-operative blood loss [weighted mean difference (WMD) 79.87, 95% CI: 65.88-93.86], more postoperative surgical complications (relative risk 1.23, 95% CI: 1.08-1.40), longer large bowel resection (WMD 47.06, 95% CI: 10.49-83.62), greater distance from the tumour to the high vascular tie (WMD 17.51, 95% CI: 15.16-19.87), larger area of mesentery (WMD 36.09, 95% CI: 18.06-54.13) and more lymph nodes (WMD 6.13, 95% CI: 1.97-10.28) than NCME. CME also had positive effects on 5-year survival [hazard ratio (HR) 0.33, 95% CI: 0.13-0.81], 3-year survival (HR 0.58, 95% CI: 0.39-0.86) and 3-year survival for Stage III disease (HR 0.69, 95% CI: 0.60-0.80) compared with NCME. CONCLUSION Limited evidence suggests that CME is a more effective strategy for improving specimen quality and survival but with a higher complication rate.
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Affiliation(s)
- C Wang
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - Z Gao
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China
| | - K Shen
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - Z Shen
- Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - K Jiang
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - B Liang
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - M Yin
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - X Yang
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - S Wang
- Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
| | - Y Ye
- Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
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Weixler B, Viehl CT, Warschkow R, Guller U, Ramser M, Sauter G, Zuber M. Comparative Analysis of Tumor Cell Dissemination to the Sentinel Lymph Nodes and to the Bone Marrow in Patients With Nonmetastasized Colon Cancer: A Prospective Multicenter Study. JAMA Surg 2017; 152:912-920. [PMID: 28593306 DOI: 10.1001/jamasurg.2017.1514] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Importance Small nodal tumor infiltrates (SNTI; isolated tumor cells and micrometastases) in sentinel lymph nodes and bone marrow micrometastases (BMM) were independently described as prognostic factors in patients with colon cancer. Objective To examine the association between the occurrence of SNTI and BMM as well as their prognostic relevance. Design, Setting, and Participants This prospective study was conducted at 3 university-affiliated institutions in Switzerland between May 2000 and December 2006. Statistical analyses were performed in October 2016. A total of 122 patients with stage I to III colon cancer were included. Follow-up time exceeded 6 years, with no patients lost to follow-up. Interventions Bone marrow aspiration from the iliac crests and in vivo sentinel lymph node mapping were performed during open standard oncological resection. Bone marrow aspirates were stained with the pancytokeratin marker A45-B/B3. All sentinel lymph nodes underwent multilevel sectioning and were stained with hematoxylin-eosin and the pancytokeratin marker AE1/AE3. Main Outcomes and Measures Association of SNTI in sentinel lymph nodes and BMM in patients with stage I to III colon cancer and the prognostic effect on disease-free survival (DFS) and overall survival (OS). Results Of the 122 patients, 63 (51.6%) were female, with a mean (SD) age of 71.2 (11.7) years. Small nodal tumor infiltrates and BMM were found in a total of 21 patients (17.2%) and 46 patients (37.7%), respectively. The occurrence of BMM was not associated with the presence of SNTI by standard correlation (κ, -0.07; 95% CI, -0.29 to 0.14; P = .49) nor by univariate logistic regression analysis (odds ratio, 0.64; 95% CI, 0.22-1.67; P = .37) or multivariate logistic regression analysis (odds ratio, 1.09; 95% CI, 0.34-3.28; P = .88). The presence of SNTI was an independent negative prognostic factor for DFS (hazard ratio [HR], 2.93; 95% CI, 1.24-6.93; P = .02) and OS (HR, 4.04; 95% CI, 1.56-10.45; P = .005), as was BMM (HR, 2.07; 95% CI, 1.06-4.06; P = .04; and HR, 2.68; 95% CI, 1.26-5.70; P = .01; respectively). The combined detection of BMM and SNTI demonstrated the poorest DFS (HR, 6.73; 95% CI, 2.29-19.76; P = .006) and OS (HR, 5.96; 95% CI, 1.66-21.49; P = .03). Conclusions and Relevance This study demonstrates no association between the occurrence of SNTI and BMM in patients with stage I to III colon cancer. However, both SNTI and BMM are independent negative prognostic factors regarding DFS and OS, and the occurrence of both is associated with significantly worse prognosis compared with either one of them. Trial Registration clinicaltrials.gov Identifier: NCT00826579.
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Affiliation(s)
- Benjamin Weixler
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Carsten T Viehl
- Department of Surgery, University Hospital Basel, Basel, Switzerland.,Department of Surgery, Hospital Center Biel, Biel/Bienne, Switzerland
| | - Rene Warschkow
- Department of Surgery, Kantonsspital St Gallen, St Gallen, Switzerland.,Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Ulrich Guller
- Department of Oncology and Hematology, Cantonal Hospital St Gallen, St Gallen, Switzerland.,University Clinic for Visceral Surgery and Medicine, Inselspital Berne, University of Berne, Berne, Switzerland
| | - Michaela Ramser
- Department of Surgery, University Hospital Basel, Basel, Switzerland
| | - Guido Sauter
- Department of Pathology, University Hospital Basel, Basel, Switzerland.,Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Markus Zuber
- Department Surgery, Cantonal Hospital Olten, Olten, Switzerland
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48
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer. Dis Colon Rectum 2017; 60:999-1017. [PMID: 28891842 DOI: 10.1097/dcr.0000000000000926] [Citation(s) in RCA: 223] [Impact Index Per Article: 27.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than to dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient.
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Stojanoski S, Manevska N, Antovic S, Pop-Gjorcheva D, Vaskova O, Miladinova D, Mileva M. Sentinel Lymph Node Detection in Colorectal Cancer - First Experience. Open Access Maced J Med Sci 2017; 5:744-750. [PMID: 29123574 PMCID: PMC5672113 DOI: 10.3889/oamjms.2017.166] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 08/01/2017] [Accepted: 08/02/2017] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND: Colorectal cancer (CRC) is the second commonest cancer in women, the third in men, being the fourth commonest cause of cancer death. The most important factor for prognosis and staging in CRC patients is the status of the regional lymph nodes (LN). AIM: To implement the method for sentinel lymph node (SLN) detection in CRC patients using radiocolloid, and test its detection rate, sensitivity, accuracy, negative predictive value and the possibility for upstaging. MATERIAL AND METHODS: The study included 40 CRC patients, age 63 ± 14 years, without LNs detected on CT or MRI. SLN detection was performed after endoscopically peri- and intratumoral injection of 99mTc-SENTISCINT. All patients underwent resection with systemic lymphadenectomy, and the SLNs were detected ex vivo. Pathohistology was performed to all resected LNs. RESULTS: The identification rate was 95%, the accuracy of the procedure was 92.1%, the negative predictive value was 86.95%, the sensitivity was 83.3%, and the upstage was 22.5%. CONCLUSION: Identification of SLNs in CRC patients with this method is possible and the detection rate, negative predictive value, accuracy and sensitivity are reliable. We expect to contribute in the upstaging of stage II CRC patients and the selection of appropriate oncology treatment protocols.
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Affiliation(s)
- Sinisa Stojanoski
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Nevena Manevska
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Svetozar Antovic
- University Clinic for Digestive Surgery, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Daniela Pop-Gjorcheva
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Olivija Vaskova
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Daniela Miladinova
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Magdalena Mileva
- Institute for Pathophysiology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
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Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients. Clin Epigenetics 2017; 9:97. [PMID: 28878843 PMCID: PMC5584052 DOI: 10.1186/s13148-017-0397-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Accepted: 08/28/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Patients with early colorectal cancer (stages I-II) generally have a good prognosis, but a subgroup of 15-20% experiences relapse and eventually die of disease. Occult metastases have been suggested as a marker for increased risk of recurrence in patients with node-negative disease. Using a previously identified, highly accurate epigenetic biomarker panel for early detection of colorectal tumors, we aimed at evaluating the prognostic value of occult metastases in sentinel lymph nodes of colon cancer patients. RESULTS The biomarker panel was analyzed by quantitative methylation-specific PCR in primary tumors and 783 sentinel lymph nodes from 201 patients. The panel status in sentinel lymph nodes showed a strong association with lymph node stage (P = 8.2E-17). Compared with routine lymph node diagnostics, the biomarker panel had a sensitivity of 79% (31/39). Interestingly, among 162 patients with negative lymph nodes from routine diagnostics, 13 (8%) were positive for the biomarker panel. Colon cancer patients with high sentinel lymph node methylation had an inferior prognosis (5-year overall survival P = 3.0E-4; time to recurrence P = 3.1E-4), although not significant. The same trend was observed in multivariate analyses (P = 1.4E-1 and P = 6.7E-2, respectively). Occult sentinel lymph node metastases were not detected in early stage (I-II) colon cancer patients who experienced relapse. CONCLUSIONS Colon cancer patients with high sentinel lymph node methylation of the analyzed epigenetic biomarker panel had an inferior prognosis, although not significant in multivariate analyses. Occult metastases in TNM stage II patients that experienced relapse were not detected.
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