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Nougaret S, Gormly K, Lambregts DMJ, Reinhold C, Goh V, Korngold E, Denost Q, Brown G. MRI of the Rectum: A Decade into DISTANCE, Moving to DISTANCED. Radiology 2025; 314:e232838. [PMID: 39772798 DOI: 10.1148/radiol.232838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Over the past decade, advancements in rectal cancer research have reshaped treatment paradigms. Historically, treatment for locally advanced rectal cancer has focused on neoadjuvant long-course chemoradiotherapy, followed by total mesorectal excision. Interest in organ preservation strategies has been strengthened by the introduction of total neoadjuvant therapy with improved rates of complete clinical response. The administration of systemic induction chemotherapy and consolidation chemoradiotherapy in the neoadjuvant setting has introduced a new dimension to the treatment landscape and patients now face a more intricate decision-making process, given the expanded therapeutic options. This complexity underlines the importance of shared decision-making and brings to light the crucial role of radiologists. MRI, especially high-spatial-resolution T2-weighted imaging, is heralded as the reference standard for rectal cancer management because of its exceptional ability to provide staging and prognostic insights. A key evolution in MRI interpretation for rectal cancer is the transition from the DISTANCE mnemonic to the more encompassing DISTANCED-DIS, distal tumor boundary; T, T stage; A, anal sphincter complex; N, nodal status; C, circumferential resection margin; E, extramural venous invasion; D, tumor deposits. This nuanced shift in the mnemonic captures a wider range of diagnostic indicators. It also emphasizes the escalating role of radiologists in steering well-informed decisions in the realm of rectal cancer care.
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Affiliation(s)
- Stephanie Nougaret
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Kirsten Gormly
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Doenja M J Lambregts
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Caroline Reinhold
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Vicky Goh
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Elena Korngold
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Quentin Denost
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
| | - Gina Brown
- From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.)
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Wang R, Lv C, Li D, Song Y, Yan Z. EEF1D stabilized by SRSF9 promotes colorectal cancer via enhancing the proliferation and metastasis. Int J Cancer 2024; 155:1487-1499. [PMID: 38771720 DOI: 10.1002/ijc.35039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 03/21/2024] [Accepted: 04/16/2024] [Indexed: 05/23/2024]
Abstract
Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull-down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3'UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.
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Affiliation(s)
- Rui Wang
- Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chi Lv
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Donghao Li
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yutong Song
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhaopeng Yan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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García-Silva S, Peinado H. Mechanisms of lymph node metastasis: An extracellular vesicle perspective. Eur J Cell Biol 2024; 103:151447. [PMID: 39116620 DOI: 10.1016/j.ejcb.2024.151447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 07/12/2024] [Accepted: 07/25/2024] [Indexed: 08/10/2024] Open
Abstract
In several solid tumors such as breast cancer, prostate cancer, colorectal cancer or melanoma, tumor draining lymph nodes are the earliest tissues where colonization by tumor cells is detected. Lymph nodes act as sentinels of metastatic dissemination, the deadliest phase of tumor progression. Besides hematogenous dissemination, lymphatic spread of tumor cells has been demonstrated, adding more complexity to the mechanisms involved in metastasis. A network of blood and lymphatic vessels surrounds tumors providing routes for tumor soluble factors to mediate regional and long-distance effects. Additionally, extracellular vesicles (EVs), particularly small EVs/exosomes, have been shown to circulate through the blood and lymph, favoring the formation of pre-metastatic niches in the tumor-draining lymph nodes (TDLNs) and distant organs. In this review, we present an overview of the relevance of lymph node metastasis, the structural and immune changes occurring in TDLNs during tumor progression, and how extracellular vesicles contribute to modulating some of these alterations while promoting the formation of lymph node pre-metastatic niches.
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Affiliation(s)
- Susana García-Silva
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
| | - Héctor Peinado
- Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
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Kazemzadeh F, Snoek JAA, Voorham QJ, van Oijen MGH, Hugen N, Nagtegaal ID. Association of metastatic pattern in breast cancer with tumor and patient-specific factors: a nationwide autopsy study using artificial intelligence. Breast Cancer 2024; 31:263-271. [PMID: 38133738 DOI: 10.1007/s12282-023-01534-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Metastatic spread is characterized by considerable heterogeneity in most cancers. With increasing treatment options for patients with metastatic disease, there is a need for insight into metastatic patterns of spread in breast cancer patients using large-scale studies. METHODS Records of 2622 metastatic breast cancer patients who underwent autopsy (1974-2010) were retrieved from the nationwide Dutch pathology databank (PALGA). Natural language processing (NLP) and manual information extraction (IE) were applied to identify the tumors, patient characteristics, and locations of metastases. RESULTS The accuracy (0.90) and recall (0.94) of the NLP model outperformed manual IE (on 132 randomly selected patients). Adenocarcinoma no special type more frequently metastasizes to the lung (55.7%) and liver (51.8%), whereas, invasive lobular carcinoma mostly spread to the bone (54.4%) and liver (43.8%), respectively. Patients with tumor grade III had a higher chance of developing bone metastases (61.6%). In a subgroup of patients, we found that ER+/HER2+ patients were more likely to metastasize to the liver and bone, compared to ER-/HER2+ patients. CONCLUSION This is the first large-scale study that demonstrates that artificial intelligence methods are efficient for IE from Dutch databanks. Different histological subtypes show different frequencies and combinations of metastatic sites which may reflect the underlying biology of metastatic breast cancer.
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Affiliation(s)
- Fatemeh Kazemzadeh
- Department of Pathology 824, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
- Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
- Therapy Program, Cancer Center Amsterdam, Amsterdam, The Netherlands.
| | - J A A Snoek
- Department of Pathology 824, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
- Department of Pathology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | | | - Martijn G H van Oijen
- Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Therapy Program, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Niek Hugen
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Surgery, Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology 824, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
- PALGA Foundation, Houten, The Netherlands.
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Jiang B, Zhou H, Xie X, Xia T, Ke C. Down-regulation of zinc finger protein 335 undermines natural killer cell function in mouse colitis-associated colorectal carcinoma. Heliyon 2024; 10:e25721. [PMID: 38375265 PMCID: PMC10875430 DOI: 10.1016/j.heliyon.2024.e25721] [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: 12/07/2022] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/21/2024] Open
Abstract
Natural killer (NK) cells constitute an active and potent anti-tumor effector population against multiple malignancies. NK cells exploit tumoricidal machinery to restrain colorectal carcinoma (CRC) expansion and invasion. Nonetheless, it is becoming increasingly evident that functional exhaustion considerably compromises the potency of NK cells in patients with CRC. To elucidate the factors that impair NK cell function in the context of CRC, we determined the role of zinc finger protein 335 (ZFP335) in modulating NK cell activity in mouse CRC induced by azoxymethane and dextran sulfate sodium. ZFP335 was profoundly decreased in NK cells in mesenteric lymph nodes of CRC-bearing mice. ZFP335 was especially diminished in NK cells that were both phenotypically and functionally exhausted. Besides, effective ZFP335 knockdown markedly undermined NK cell proliferation, tumoricidal protein production, degranulation, and cytotoxic efficacy on malignant cells, strongly suggesting that ZFP335 reinforces NK cell function. Importantly, ZFP335 knockdown lowered the expression of Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3), both of which play crucial roles in NK cell homeostasis and activation. Collectively, ZFP335 down-regulation is essential for NK cell exhaustion in mesenteric lymph nodes of mice with CRC. We discovered a new ZFP335-JAK1/3 signaling pathway that modulates NK cell exhaustion.
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Affiliation(s)
- Bin Jiang
- The Department of Gastrointestinal, Hernia, and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, 430060, China
| | - Hongjian Zhou
- The Department of Gastrointestinal, Hernia, and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, 430060, China
| | - Xingwang Xie
- The Department of Gastrointestinal, Hernia, and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, 430060, China
| | - Tian Xia
- The Department of Gastrointestinal, Hernia, and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, 430060, China
| | - Chao Ke
- The Department of Gastrointestinal, Hernia, and Abdominal Wall Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei Province, 430060, China
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Schneider N, Hermann PC, Eiseler T, Seufferlein T. Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy. Cancers (Basel) 2024; 16:567. [PMID: 38339318 PMCID: PMC10854789 DOI: 10.3390/cancers16030567] [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: 12/13/2023] [Revised: 01/22/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
Discovered in the late eighties, sEVs are small extracellular nanovesicles (30-150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.
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Affiliation(s)
- Nora Schneider
- Department for Internal Medicine 1, University Clinic Ulm, 89081 Ulm, Germany; (P.C.H.); (T.S.)
| | | | - Tim Eiseler
- Correspondence: (N.S.); (T.E.); Tel.: +49-731-500-44678 (N.S.); +49-731-500-44523 (T.E.)
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Selvaggi F, Catalano T, Lattanzio R, Cotellese R, Aceto GM. Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities. World J Gastroenterol 2023; 29:2764-2783. [PMID: 37274070 PMCID: PMC10237106 DOI: 10.3748/wjg.v29.i18.2764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/28/2023] [Accepted: 04/17/2023] [Indexed: 05/11/2023] Open
Abstract
The liver is the most common site of metastases in patients with colorectal cancer. Colorectal liver metastases (CRLMs) are the result of molecular mechanisms that involve different cells of the liver microenvironment. The aberrant activation of Wingless/It (Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium, but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymal-epithelial transition interactions. In liver microenvironment, metastatic cells can also survive and adapt through dormancy, which makes them less susceptible to pro-apoptotic signals and therapies. Treatment of CRLMs is challenging due to its variability and heterogeneity. Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been re-cognized in chemoresistance. At the state of art, there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie. In this review, current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered. In addition, an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.
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Affiliation(s)
- Federico Selvaggi
- Department of Surgical, ASL2 Lanciano-Vasto-Chieti, Ospedale Clinicizzato SS Annunziata of Chieti, Chieti 66100, Italy
| | - Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, Messina 98125, Italy
| | - Rossano Lattanzio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
| | - Roberto Cotellese
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Chieti 66100, Italy
- Villa Serena Foundation for Research, Villa Serena - Del Dott. L. Petruzzi, Città Sant’Angelo 65013, Pescara, Italy
| | - Gitana Maria Aceto
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
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Hermans KEPE, Kazemzadeh F, Loef C, Jansen RLH, Nagtegaal ID, van den Brandt PA, Schouten LJ. Risk factors for cancer of unknown primary: a literature review. BMC Cancer 2023; 23:314. [PMID: 37020279 PMCID: PMC10077635 DOI: 10.1186/s12885-023-10794-6] [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: 10/17/2022] [Accepted: 03/30/2023] [Indexed: 04/07/2023] Open
Abstract
Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. Epidemiological studies on possible CUP risk factors were systematically searched in PubMed and Web of Science on February 1st, 2022. Studies, published before 2022, were included if they were observational human-based, provided relative risk estimates, and investigated possible CUP risk factors. A total of 5 case-control and 14 cohort studies were included. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. No other CUP risk factors have been studied. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.
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Affiliation(s)
- Karlijn E P E Hermans
- Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands.
| | - Fatemeh Kazemzadeh
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Caroline Loef
- Department of Research, Comprehensive Cancer Organization the Netherlands, Utrecht, the Netherlands
| | - Rob L H Jansen
- Department of Research, Comprehensive Cancer Organization the Netherlands, Utrecht, the Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Piet A van den Brandt
- Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands
| | - Leo J Schouten
- Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands
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Causa Andrieu P, Golia Pernicka JS, Yaeger R, Lupton K, Batch K, Zulkernine F, Simpson AL, Taya M, Gazit L, Nguyen H, Nicholas K, Gangai N, Sevilimedu V, Dickinson S, Paroder V, Bates DD, Do R. Natural Language Processing of Computed Tomography Reports to Label Metastatic Phenotypes With Prognostic Significance in Patients With Colorectal Cancer. JCO Clin Cancer Inform 2022; 6:e2200014. [PMID: 36103642 PMCID: PMC9848599 DOI: 10.1200/cci.22.00014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 06/04/2022] [Accepted: 08/04/2022] [Indexed: 01/21/2023] Open
Abstract
PURPOSE Natural language processing (NLP) applied to radiology reports can help identify clinically relevant M1 subcategories of patients with colorectal cancer (CRC). The primary purpose was to compare the overall survival (OS) of CRC according to American Joint Committee on Cancer TNM staging and explore an alternative classification. The secondary objective was to estimate the frequency of metastasis for each organ. METHODS Retrospective study of CRC who underwent computed tomography (CT) chest, abdomen, and pelvis between July 1, 2009, and March 26, 2019, at a tertiary cancer center, previously labeled for the presence or absence of metastasis by an NLP prediction model. Patients were classified in M0, M1a, M1b, and M1c (American Joint Committee on Cancer), or an alternative classification on the basis of the metastasis organ number: M1, single; M2, two; M3, three or more organs. Cox regression models were used to estimate hazard ratios; Kaplan-Meier curves were used to visualize survival curves using the two M1 subclassifications. RESULTS Nine thousand nine hundred twenty-eight patients with a total of 48,408 CT chest, abdomen, and pelvis reports were included. On the basis of NLP prediction, the median OS of M1a, M1b, and M1c was 4.47, 1.72, and 1.52 years, respectively. The median OS of M1, M2, and M3 was 4.24, 2.05, and 1.04 years, respectively. Metastases occurred most often in liver (35.8%), abdominopelvic lymph nodes (32.9%), lungs (29.3%), peritoneum (22.0%), thoracic nodes (19.9%), bones (9.2%), and pelvic organs (7.5%). Spleen and adrenal metastases occurred in < 5%. CONCLUSION NLP applied to a large radiology report database can identify clinically relevant metastatic phenotypes and be used to investigate new M1 substaging for CRC. Patients with three or more metastatic disease organs have the worst prognosis, with an OS of 1 year.
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Affiliation(s)
| | | | - Rona Yaeger
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kaelan Lupton
- School of Computing, Queens University, Kingston, Canada
| | - Karen Batch
- School of Computing, Queens University, Kingston, Canada
| | | | | | - Michio Taya
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Lior Gazit
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Huy Nguyen
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kevin Nicholas
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Natalie Gangai
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Varadan Sevilimedu
- Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Shannan Dickinson
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David D.B. Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Richard Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
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Xu J, Ma Y, Mei H, Wang Q. Diagnostic Value of Multimodal Magnetic Resonance Imaging in Discriminating Between Metastatic and Non-Metastatic Pelvic Lymph Nodes in Cervical Cancer. Int J Gen Med 2022; 15:6279-6288. [PMID: 35911622 PMCID: PMC9326496 DOI: 10.2147/ijgm.s372154] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 07/08/2022] [Indexed: 11/23/2022] Open
Abstract
Background The status of pelvic lymph node (PLN) metastasis affects treatment and prognosis plans in patients with cervical cancer. However, it is hard to be diagnosed in clinical practice. Purpose The present study aimed to evaluate the diagnostic value of multimodal magnetic resonance imaging (MRI) in discriminating between metastatic and non-metastatic pelvic lymph nodes (PLNs) in cervical cancer. Methods This retrospective study analyzed MRIs of 209 PLNs in 25 women with pathologically proven cervical cancer. All PLNs had been assessed by pre-treatment multimodal MRIs, and their status was finally confirmed by histopathology. In conventional MRI, lymph node characteristics were compared between metastatic and non-metastatic PLNs. Signal intensity, time–intensity curve (TIC) patterns minimal and mean apparent diffusion coefficients (ADC) were compared between them in DWI. In DCE-MRI, quantitative (Ktrans, Kep and Ve) analyses were performed on DCE-MRI sequences, and their predictive values were analyzed by ROC curves. Results Of 209 PLNs, 22 (10.53%) were metastases and 187 (89.47%) were non-metastases at histopathologic examination. Considering a comparison of lymph node characteristics, the short axis size, the long axis size, and the boundary differed significantly between the two groups (P<0.05).The differences in ADCmin, TIC types, Ktrans and Ve between metastatic and non-metastatic PLNs were significant as well (P<0.05). The good diagnostic performance of multimodal MRI was shown in discriminating between metastatic and non-metastatic PLNs, with the sensitivity of 85.0% (17/20), specificity of 97.3% (184/189), and accuracy of 96.2% (201/209). ROC analyses showed that the diagnostic accuracy of ADCmin, Ktrans and Ve for discriminating between metastatic and non-metastatic PLNs in cervical cancer was 83.7%, 91.4%, and 92.4% with the cut-off values of 0.72 × 10−3mm2/s, 0.52 min−1, and 0.53 min−1, respectively. Conclusion Multimodal MRI showed good diagnostic performance in determining PLN status in cervical cancer.
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Affiliation(s)
- Jian Xu
- Department of Radiology, Ningbo Women & Children's Hospital, Ningbo, People's Republic of China
| | - Yingli Ma
- Department of Neurology, Ningbo Hospital of Traditional Chinese Medicine, Ningbo, People's Republic of China
| | - Haibing Mei
- Department of Radiology, Ningbo Women & Children's Hospital, Ningbo, People's Republic of China
| | - Qimin Wang
- Department of Radiology, Ningbo Women & Children's Hospital, Ningbo, People's Republic of China
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High-Throughput Profiling of Colorectal Cancer Liver Metastases Reveals Intra- and Inter-Patient Heterogeneity in the EGFR and WNT Pathways Associated with Clinical Outcome. Cancers (Basel) 2022; 14:cancers14092084. [PMID: 35565214 PMCID: PMC9104154 DOI: 10.3390/cancers14092084] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Tumor heterogeneity can greatly influence therapy outcome and patient survival. In this study, we aimed at unraveling inter- and intra-patient heterogeneity of colorectal cancer liver metastases (CRLM). To this end, we comprehensively characterized CRLM using state-of-the-art high-throughput technologies combined with bioinformatics analyses. We found a high degree of inter- and intra-patient heterogeneity among the metastases, in particular in genes of the WNT and EGFR pathways. Through analyzing the master regulators and effectors associated with the regulation of these genes, we identified a specific gene signature that was highly expressed in a large cohort of colorectal cancer patients and associated with clinical outcome. Abstract Seventy percent of patients with colorectal cancer develop liver metastases (CRLM), which are a decisive factor in cancer progression. Therapy outcome is largely influenced by tumor heterogeneity, but the intra- and inter-patient heterogeneity of CRLM has been poorly studied. In particular, the contribution of the WNT and EGFR pathways, which are both frequently deregulated in colorectal cancer, has not yet been addressed in this context. To this end, we comprehensively characterized normal liver tissue and eight CRLM from two patients by standardized histopathological, molecular, and proteomic subtyping. Suitable fresh-frozen tissue samples were profiled by transcriptome sequencing (RNA-Seq) and proteomic profiling with reverse phase protein arrays (RPPA) combined with bioinformatic analyses to assess tumor heterogeneity and identify WNT- and EGFR-related master regulators and metastatic effectors. A standardized data analysis pipeline for integrating RNA-Seq with clinical, proteomic, and genetic data was established. Dimensionality reduction of the transcriptome data revealed a distinct signature for CRLM differing from normal liver tissue and indicated a high degree of tumor heterogeneity. WNT and EGFR signaling were highly active in CRLM and the genes of both pathways were heterogeneously expressed between the two patients as well as between the synchronous metastases of a single patient. An analysis of the master regulators and metastatic effectors implicated in the regulation of these genes revealed a set of four genes (SFN, IGF2BP1, STAT1, PIK3CG) that were differentially expressed in CRLM and were associated with clinical outcome in a large cohort of colorectal cancer patients as well as CRLM samples. In conclusion, high-throughput profiling enabled us to define a CRLM-specific signature and revealed the genes of the WNT and EGFR pathways associated with inter- and intra-patient heterogeneity, which were validated as prognostic biomarkers in CRC primary tumors as well as liver metastases.
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Nougaret S, Rousset P, Gormly K, Lucidarme O, Brunelle S, Milot L, Salut C, Pilleul F, Arrivé L, Hordonneau C, Baudin G, Soyer P, Brun V, Laurent V, Savoye-Collet C, Petkovska I, Gerard JP, Rullier E, Cotte E, Rouanet P, Beets-Tan RGH, Frulio N, Hoeffel C. Structured and shared MRI staging lexicon and report of rectal cancer: A consensus proposal by the French Radiology Group (GRERCAR) and Surgical Group (GRECCAR) for rectal cancer. Diagn Interv Imaging 2022; 103:127-141. [PMID: 34794932 DOI: 10.1016/j.diii.2021.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 08/13/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE To develop French guidelines by experts to standardize data acquisition, image interpretation, and reporting in rectal cancer staging with magnetic resonance imaging (MRI). MATERIALS AND METHODS Evidence-based data and opinions of experts of GRERCAR (Groupe de REcherche en Radiologie sur le CAncer du Rectum [i.e., Rectal Cancer Imaging Research Group]) and GRECCAR (Groupe de REcherche en Chirurgie sur le CAncer du Rectum [i.e., Rectal Cancer Surgery Research Group]) were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts scoring of reporting template and protocol for data acquisition were collected; responses were analyzed and classified as "Recommended" versus "Not recommended" (when ≥ 80% consensus among experts) or uncertain (when < 80% consensus among experts). RESULTS Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION These consensus recommendations should be used as a guide for rectal cancer staging with MRI.
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Affiliation(s)
- Stephanie Nougaret
- Department of Radiology, Institut Régional du Cancer de Montpellier, Montpellier Cancer Research Institute, INSERM U1194, University of Montpellier, 34295, Montpellier, France.
| | - Pascal Rousset
- Department of Radiology, Lyon 1 Claude-Bernard University, 69495 Pierre-Benite, France
| | - Kirsten Gormly
- Dr Jones & Partners Medical Imaging, Kurralta Park, 5037, Australia; University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia
| | - Oliver Lucidarme
- Department of Radiology, Pitié-Salpêtrière Hospital, Sorbonne Université, 75013 Paris, France; LIB, INSERM, CNRS, UMR7371-U1146, 75013 Paris, France
| | - Serge Brunelle
- Department of Radiology, Institut Paoli-Calmettes, 13009 Marseille, France
| | - Laurent Milot
- Radiology Department, Hospices Civils de Lyon, Lyon Sud University Hospital, 69495 Pierre Bénite, France; Lyon 1 Claude Bernard University, 69100 Villeurbanne, France
| | - Cécile Salut
- Department of Radiology, CHU de Bordeaux, Université de Bordeaux, 33000 Bordeaux, France
| | - Franck Pilleul
- Department of Radiology, Centre Léon Bérard, Lyon, France Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, 69621, Lyon, France
| | - Lionel Arrivé
- Department of Radiology, Hopital St Antoine, Paris, France
| | - Constance Hordonneau
- Department of Radiology, CHU Estaing, Université Clermont-Auvergne, 63000 Clermont-Ferrand, France
| | - Guillaume Baudin
- Department of Radiology, Centre Antoine Lacassagne, 06100 Nice, France
| | - Philippe Soyer
- Department of Radiology, Hôpital Cochin, AP-HP, 75014 Paris, France; Université de Paris, 75006 Paris, France
| | - Vanessa Brun
- Department of Radiology, CHU Hôpital Pontchaillou, 35000 Rennes Cedex, France
| | - Valérie Laurent
- Department of Radiology, Brabois-Nancy University Hospital, Université de Lorraine, 54500 Vandoeuvre-lès-Nancy, France
| | | | - Iva Petkovska
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Jean Pierre Gerard
- Department of Radiotherapy, Centre Antoine Lacassagne, 06100 Nice, France
| | - Eric Rullier
- Department of Digestive Surgery, Hôpital Haut-Lévèque, Université de Bordeaux, 33600 Pessac, France
| | - Eddy Cotte
- Department of Digestive Surgery, Hospices Civils de Lyon, Lyon Sud University Hospital, 69310 Pierre Bénite, France; Lyon 1 Claude Bernard University, 69100 Villeurbanne, France
| | - Philippe Rouanet
- Department of surgery, Institut Régional du Cancer de Montpellier, Montpellier Cancer Research Institute, INSERM U1194, University of Montpellier, 34295, Montpellier, France
| | - Regina G H Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute, 1066 CX, Amsterdam, the Netherlands
| | - Nora Frulio
- Department of Radiology, CHU de Bordeaux, Université de Bordeaux, 33000 Bordeaux, France
| | - Christine Hoeffel
- Department of Radiology, Hôpital Robert Debré & CRESTIC, URCA, 51092 Reims, France
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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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Zhuang Z, Zhang Y, Wei M, Yang X, Wang Z. Magnetic Resonance Imaging Evaluation of the Accuracy of Various Lymph Node Staging Criteria in Rectal Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2021; 11:709070. [PMID: 34327144 PMCID: PMC8315047 DOI: 10.3389/fonc.2021.709070] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 06/22/2021] [Indexed: 02/05/2023] Open
Abstract
Background Magnetic resonance imaging (MRI)-based lymph node staging remains a significant challenge in the treatment of rectal cancer. Pretreatment evaluation of lymph node metastasis guides the formulation of treatment plans. This systematic review aimed to evaluate the diagnostic performance of MRI in lymph node staging using various morphological criteria. Methods A systematic search of the EMBASE, Medline, and Cochrane databases was performed. Original articles published between 2000 and January 2021 that used MRI for lymph node staging in rectal cancer were eligible. The included studies were assessed using the QUADAS-2 tool. A bivariate random-effects model was used to conduct a meta-analysis of diagnostic test accuracy. Results Thirty-seven studies were eligible for this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of preoperative MRI for the lymph node stage were 0.73 (95% confidence interval [CI], 0.68–0.77), 0.74 (95% CI, 0.68–0.80), and 7.85 (95% CI, 5.78–10.66), respectively. Criteria for positive mesorectal lymph node metastasis included (A) a short-axis diameter of 5 mm, (B) morphological standard, including an irregular border and mixed-signal intensity within the lymph node, (C) a short-axis diameter of 5 mm with the morphological standard, (D) a short-axis diameter of 8 mm with the morphological standard, and (E) a short-axis diameter of 10 mm with the morphological standard. The pooled sensitivity/specificity for these criteria were 75%/64%, 81%/67%, 74%/79%, 72%/66%, and 62%/91%, respectively. There was no significant difference among the criteria in sensitivity/specificity. The area under the receiver operating characteristic (ROC) curve values of the fitted summary ROC indicated a diagnostic accuracy rate of 0.75–0.81. Conclusion MRI scans have minimal accuracy as a reference index for pretreatment staging of various lymph node staging criteria in rectal cancer. Multiple types of evidence should be used in clinical decision-making.
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Affiliation(s)
- Zixuan Zhuang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Mingtian Wei
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xuyang Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ziqiang Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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15
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Verstegen MHP, Harker M, Water CVD, Dieren JV, Hugen N, Nagtegaal ID, Rosman C, Post RSVD. Metastatic pattern in esophageal and gastric cancer: Influenced by site and histology. World J Gastroenterol 2020; 26:6037-6046. [PMID: 33132653 PMCID: PMC7584055 DOI: 10.3748/wjg.v26.i39.6037] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/28/2020] [Accepted: 09/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited. Early recognition of metastases is important to avoid futile locoregional treatments. Furthermore, knowledge on metastatic patterns is necessary for further development of personalized treatment modalities.
AIM To gain insight into the metastatic pattern of gastroesophageal cancer.
METHODS A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus or stomach between 1990 and 2017 was performed. Only patient with metastases were included for analysis. The metastatic pattern was analyzed according to the primary tumor location and histological subtype.
RESULTS Metastatic disease was found in 268 esophageal and 331 gastric cancer patients. In esophageal cancer, the most common metastatic locations were liver (56%), distant lymph nodes (53%) and lung (50%). Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC. In gastric cancer, the most common metastatic locations were distant lymph nodes (56%), liver (53%) and peritoneum (51%). Intestinal-type AC of the stomach showed metastases to the liver more frequently, whereas metastases to the bone, female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC.
CONCLUSION This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.
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Affiliation(s)
- Moniek HP Verstegen
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Mitchell Harker
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Carlijn van de Water
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Jolanda van Dieren
- Department of Gastroenterology Oncology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Niek Hugen
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Camiel Rosman
- Department of Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
| | - Rachel S van der Post
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Radboud University Medical Center, Nijmegen 6525 GA, Netherlands
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Zaręba KP, Zińczuk J, Dawidziuk T, Rosołowski M, Pryczynicz A, Guzińska-Ustymowicz K, Kędra B. Can factors that influence nodal dissemination in patients with colorectal cancer be identified? Own experience. PRZEGLAD GASTROENTEROLOGICZNY 2020; 15:247-252. [PMID: 33005271 PMCID: PMC7509900 DOI: 10.5114/pg.2020.98542] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 10/01/2019] [Indexed: 12/01/2022]
Abstract
INTRODUCTION As one of the most common causes of cancer deaths in Poland, colorectal cancer, remains a mystery when factors affecting local and distant lymph node metastasis are concerned. AIM In this study the authors have analysed possible correlations between the number of regional (and distant) lymph nodes affected by cancer, location and stage of the primary tumour, levels of oncological markers CA19-9 and CEA, and the patients age, sex, body mass index (BMI), and other clinical symptoms. MATERIAL AND METHODS A special questionnaire was created for this study, and a group of 100 men and women was selected. All patients in the study group had undergone surgery due to colorectal cancer. RESULTS There were no statistically significant relationships between age, and number and location of metastases (p > 0.05). Primary tumour assessment did not show a statistically significant relationship with the presence of metastases to regional lymph nodes (p > 0.05). There was also no statistically significant correlation between tumour localisation and lymph node metastases (p > 0.05) or between tumour size, BMI, occurrence of physical symptoms, and involvement of distant lymph nodes (p > 0.05). The highest CEA was observed in a patient with nine regional lymph node metastases (612.46 ng/ml) and the lowest in one with metastases to two regional nodes (0.2 U/ml). CEA value above 5 ng/ml was found in 35.74% of patients with regional lymph node metastases. A statistically significant relationship was reported (p < 0.05). CONCLUSIONS The location of the primary tumour, and its pathological stage and size does not seem to have a direct correlation with the occurrence of regional lymph node metastases. Metastasis to distant lymph nodes seems to be a consequence of metastases in regional nodes. Elevated CEA tumour marker values are significantly related to metastases in regional lymph nodes. The elevation of CA 19-9 and CEA tumour markers significantly correlates with the presence of metastasis to distant lymph nodes. The location of the primary tumour determines the formation of metastases in distant lymph nodes.
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Affiliation(s)
- Konrad P Zaręba
- 2nd Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland
| | - Justyna Zińczuk
- Department of Clinical Laboratory Diagnostic, Medical University of Bialystok, Bialystok, Poland
| | - Tomasz Dawidziuk
- Department of Thoracic Surgery, Medical University of Bialystok, Bialystok, Poland
| | - Mariusz Rosołowski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Anna Pryczynicz
- Department of Pathomorphology, Medical University of Bialystok, Bialystok, Poland
| | | | - Bogusław Kędra
- 2nd Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland
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MRI-Diagnosed Tumour Deposits and EMVI Status Have Superior Prognostic Accuracy to Current Clinical TNM Staging in Rectal Cancer. Ann Surg 2020; 276:334-344. [DOI: 10.1097/sla.0000000000004499] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Newland RC, Chan C, Chapuis PH, Keshava A, Rickard MJFX, Stewart P, Suen M, Lee K, Dent OF. Relative effects of direct spread, lymph node metastasis and venous invasion in relation to blood borne distant metastasis present at the time of resection of colorectal cancer. Pathology 2020; 52:649-656. [PMID: 32782217 DOI: 10.1016/j.pathol.2020.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 05/29/2020] [Accepted: 06/16/2020] [Indexed: 01/05/2023]
Abstract
Conventionally, lymphatic spread is regarded as the principal mechanism by which haematogenous metastasis occurs in colorectal cancer. The aim of this cross sectional study was to determine the relative strengths of direct tumour spread, the presence of lymph node metastasis and histologically demonstrated venous invasion as drivers of haematogenous metastasis diagnosed at the time of resection of colorectal cancer. The data were drawn from a hospital database of consecutive bowel cancer resections between 1995 and 2017 inclusive. The presence of haematogenous metastasis was determined at the time of surgery by imaging or other investigations or operative findings. Where possible, histological confirmation was obtained. Specimen dissection and reporting followed a standardised procedure. Tumour staging was according to the 7th edition of the UICC/AJCC pTNM system. Analysis was by multivariable logistic regression. After exclusions 3133 patients remained, among whom 380 (12.1%) had one or more haematogenous metastases. In bivariate analyses, the frequency of haematogenous metastasis was directly associated with increasing T status (p<0.001), increasing N status (p<0.001) and increasing extent of venous invasion (p<0.001) and with some other patient and tumour features. In a multivariable model, after adjustment for other features, associations with the occurrence of haematogenous metastasis were as follows: T3 odds ratio (OR) 4.41 (95% confidence interval 2.40-8.10), p<0.001; T4a OR 6.29 (3.27-12.10), p<0.001; T4b OR 5.50 (2.71-11.15), p<0.001; N1 OR 3.39 (2.47-4.64), p<0.001; N2 OR 4.59 (3.21-6.54), p<0.001; mural venous invasion OR 2.18 (1.14-4.16), p=0.018; extramural venous invasion OR 2.91 (2.21-3.83), p<0.001. Only three other features had significant, though weak effects in the model. These results led to the conclusion that venous invasion, demonstrated histologically and also inferred independently by the extent of direct tumour spread, made a greater contribution to the occurrence of haematogenous metastasis than did spread through lymphatics. Our approach and findings may have implications for other cancer sites apart from colorectal cancer.
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Affiliation(s)
- R C Newland
- Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - C Chan
- Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Division of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - P H Chapuis
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia
| | - A Keshava
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia
| | - M J F X Rickard
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia
| | - P Stewart
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia
| | - M Suen
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia
| | - K Lee
- Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Division of Anatomical Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia
| | - O F Dent
- Colorectal Surgical Unit, Concord Repatriation General Hospital, Sydney, NSW, Australia; Discipline of Surgery, Sydney Medical School, Sydney, NSW, Australia.
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Brouwer NPM, Hugen N, Nagtegaal ID. More extensive lymphadenectomy in colon cancer; how far are we willing to go for a biomarker? Tech Coloproctol 2020; 24:761-764. [PMID: 32451806 PMCID: PMC7297704 DOI: 10.1007/s10151-020-02239-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 05/13/2020] [Indexed: 02/07/2023]
Affiliation(s)
- N P M Brouwer
- Department of Pathology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
| | - N Hugen
- Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
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20
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Lord AC, Knijn N, Brown G, Nagtegaal ID. Pathways of spread in rectal cancer: a reappraisal of the true routes to distant metastatic disease. Eur J Cancer 2020; 128:1-6. [PMID: 32109846 DOI: 10.1016/j.ejca.2019.12.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 12/13/2019] [Accepted: 12/26/2019] [Indexed: 02/07/2023]
Abstract
Rectal cancer can spread in a number of ways which have been previously recognised and validated as prognostic markers. These routes of spread are not adequately recognised in the stage grouping of the tumour-node-metastasis system, which focuses predominantly on the depth of invasion and nodal status, thus limiting its prognostic accuracy. Tumour spread involving veins occurs in 40% of patients. Venous channels have greater direct access to distant sites by means of a vascular 'anatomical highway'. This rapid spread of tumour cells to distant metastatic sites by veins cannot occur by means of lymph node pathways. Thus, lymph nodes have been overestimated in their importance. Distinction between local tumour spread (lymph node metastases, perineural and lymphatic invasion) and tumour spread mediated by a direct vascular pathway to distant dissemination (extramural venous invasion and tumour deposits) must be made as the implications for prognosis and choice of treatment are not likely to be equal. Improved precision of radiological and pathological assessment is needed to scrutinise and carefully document each route of tumour spread. Only with this accurate information will it be possible to correctly weight each feature and develop a more prognostically accurate staging method that would allow separation of true high- and low-risk groups and subsequent improvements in patient care.
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Affiliation(s)
- Amy C Lord
- Royal Marsden Hospital, London, UK; Croydon University Hospital, UK; Imperial College London, UK
| | - Nikki Knijn
- Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Gina Brown
- Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK; Imperial College London, UK.
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21
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Hugen N, Sloot YJE, Netea-Maier RT, van de Water C, Smit JWA, Nagtegaal ID, van Engen-van Grunsven ICH. Divergent Metastatic Patterns Between Subtypes of Thyroid Carcinoma Results From the Nationwide Dutch Pathology Registry. J Clin Endocrinol Metab 2020; 105:5602698. [PMID: 31641763 PMCID: PMC7112975 DOI: 10.1210/clinem/dgz078] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 10/14/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Metastatic disease is the main cause of cancer-related mortality in thyroid carcinoma (TC) patients. Clinical studies have suggested differences in metastatic patterns between the different subtypes of TC. This study systematically evaluates the metastatic patterns of different subtypes in TC patients. METHODS A nationwide review of pathological records of all 650 patients diagnosed with a primary malignancy in the thyroid who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA). RESULTS Metastatic disease was present in 228 (35.1%) patients and was found in 38.7%, 17.3%, 75.4%, and 47.8% of patients with follicular, papillary, anaplastic, and medullary types of TC, respectively (P < .0001). The majority of patients had more than 1 metastasis. The most common site of metastatic disease was the lung for papillary (79.7%), follicular (72.9%), and anaplastic (92.1%) carcinoma but not for medullary carcinoma (56.3%), P < .0001. Medullary carcinoma patients most frequently had metastases to the liver (81.3%). The combination of metastases also differed between subtypes. CONCLUSION There are major differences in metastatic patterns between different subtypes of TC. The patterns and frequencies identified in this autopsy study may reflect the underlying biology of metastatic thyroid cancer and have potential to influence future monitoring and treatment strategies depending on clinical correlations.
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Affiliation(s)
- Niek Hugen
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
- Correspondence and Reprint Requests: Niek Hugen, Department of Surgery, Radboud University Medical Center, P.O. Box 9101, HP690, 6500 HB Nijmegen, the Netherlands. E-mail:
| | - Yvette J E Sloot
- Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Romana T Netea-Maier
- Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Carlijn van de Water
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jan W A Smit
- Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
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22
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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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23
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Jacobson R, Sherman SK, Dahdaleh F, Turaga KK. Peritoneal Metastases in Colorectal Cancer. Ann Surg Oncol 2018; 25:2145-2151. [PMID: 29748885 DOI: 10.1245/s10434-018-6490-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Indexed: 12/30/2022]
Affiliation(s)
- Richard Jacobson
- Department of Surgery, University of Chicago, Chicago, IL, USA.,Department of Surgery, Rush University Medical Center, Chicago, IL, USA
| | - Scott K Sherman
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | | | - Kiran K Turaga
- Department of Surgery, University of Chicago, Chicago, IL, USA.
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24
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Siddiqui M, Nagtegaal I, Santiago I, Knijn N, Berho M, Mirnezami A, Rao S, Brown G. Session 2: What causes liver metastases - lymph nodes or is it something else? Colorectal Dis 2018; 20 Suppl 1:39-42. [PMID: 29878686 DOI: 10.1111/codi.14077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The traditional view of progression of disease in cancer is the sequential spread of tumour to locoregional lymph nodes and then to distant metastases. However, this view may need to be challenged and modern pathology techniques such as immunohistochemistry and tumour profiling can provide us with a greater insight into the pathways and mechanisms of distant spread. Professor Nagtegaal discusses the evidence for reconsidering the current paradigm and reflects on the need for further investigation into mechanisms of distant metastatic spread.
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Affiliation(s)
- M Siddiqui
- Royal Marsden NHS Foundation Trust, London, UK.,Croydon University Hospital, Croydon, UK
| | - I Nagtegaal
- Radboud University Medical Care Academy, Nijmegen, The Netherlands
| | - I Santiago
- Champalimaud Foundation, Lisbon, Portugal
| | - N Knijn
- Radboud University Medical Care Academy, Nijmegen, The Netherlands
| | - M Berho
- Pathology and Laboratory Medicine, Cleveland Clinic, Weston, Florida, USA
| | | | - S Rao
- Royal Marsden NHS Foundation Trust, London, UK
| | - G Brown
- Royal Marsden NHS Foundation Trust, London, UK.,Imperial College London, London, UK
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25
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Holzner S, Brenner S, Atanasov AG, Senfter D, Stadler S, Nguyen CH, Fristiohady A, Milovanovic D, Huttary N, Krieger S, Bago-Horvath Z, de Wever O, Tentes I, Özmen A, Jäger W, Dolznig H, Dirsch VM, Mader RM, Krenn L, Krupitza G. Intravasation of SW620 colon cancer cell spheroids through the blood endothelial barrier is inhibited by clinical drugs and flavonoids in vitro. Food Chem Toxicol 2017; 111:114-124. [PMID: 29129665 DOI: 10.1016/j.fct.2017.11.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/06/2017] [Accepted: 11/08/2017] [Indexed: 12/14/2022]
Abstract
Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called "circular chemorepellent induced defects" (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-κB in SW620 cells or BECs, respectively, caused attenuation of CCIDs. The FDA approved drugs vinpocetine [inhibiting ALOX12-dependent 12(S)-HETE synthesis], ketotifen [inhibiting NF-κB], carbamazepine and fenofibrate [inhibiting 12(S)-HETE and NF-κB] significantly attenuated CCID formation at low μM concentrations. In the 5-FU-resistant SW620-R/BEC model guanfacine, nifedipine and proadifen inhibited CCIDs stronger than in the naïve SW620/BEC model. This indicated that in SW620-R cells formerly silent (yet unidentified) genes became expressed and targetable by these drugs in course of resistance acquisition. Fenofibrate, and the flavonoids hispidulin and apigenin, which are present in medicinal plants, spices, herbs and fruits, attenuated CCID formation in both, naïve- and resistant models. As FDA-approved drugs and food-flavonoids inhibited established and acquired intravasative pathways and attenuated BEC barrier-breaching in vitro, this warrants testing of these compounds in CRC models in vivo.
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Affiliation(s)
- Silvio Holzner
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | - Stefan Brenner
- Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
| | - Atanas Georgiev Atanasov
- Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
| | - Daniel Senfter
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | - Serena Stadler
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | - Chi Huu Nguyen
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | - Adryan Fristiohady
- Clinical Institute of Pathology, Medical University of Vienna, Austria; Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
| | | | - Nicole Huttary
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | - Sigurd Krieger
- Clinical Institute of Pathology, Medical University of Vienna, Austria
| | | | - Oliver de Wever
- Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent B-9000, Belgium
| | - Ioannis Tentes
- Department of Biochemistry, Medical School, Democritus University of Thrace, 681 00 Dragana/Alexandroupolis, Greece
| | - Ali Özmen
- Adnan Menderes University, Faculty of Science and Art, Department of Biology, 09010 Aydin, Turkey
| | - Walter Jäger
- Department of Clinical Pharmacy and Diagnostics, University of Vienna, A-1090 Vienna, Austria
| | - Helmut Dolznig
- Department of Medical Genetics, Medical University of Vienna, A-1090 Vienna, Austria
| | - Verena Maria Dirsch
- Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
| | - Robert Michael Mader
- Department of Medicine I, Comprehensive Cancer Center of the Medical University of Vienna, A-1090 Vienna, Austria
| | - Liselotte Krenn
- Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
| | - Georg Krupitza
- Clinical Institute of Pathology, Medical University of Vienna, Austria.
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26
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Nagtegaal ID, Schmoll HJ. Colorectal cancer: What is the role of lymph node metastases in the progression of colorectal cancer? Nat Rev Gastroenterol Hepatol 2017; 14:633-634. [PMID: 28930293 DOI: 10.1038/nrgastro.2017.122] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Iris D Nagtegaal
- Department of Pathology, Nijmegen Medical Centre, Radboud University, PO Box 9101, 6500 HB, Nijmegen, Netherlands
| | - Hans-Joachim Schmoll
- Division of Clinical Oncology Research, University Clinic Halle (Saale), Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle (Saale), Germany
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27
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Lord AC, D'Souza N, Pucher PH, Moran BJ, Abulafi AM, Wotherspoon A, Rasheed S, Brown G. Significance of extranodal tumour deposits in colorectal cancer: A systematic review and meta-analysis. Eur J Cancer 2017. [DOI: 10.1016/j.ejca.2017.05.027] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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28
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Distinct metastatic patterns in colorectal cancer patients based on primary tumour location. Eur J Cancer 2017; 75:3-4. [PMID: 28214423 DOI: 10.1016/j.ejca.2017.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 01/02/2017] [Indexed: 01/05/2023]
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29
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Balyasnikova S, Haboubi N, Moran B, Brown G. Histopathological and radiological reporting in rectal cancer: concepts and controversies, facts and fantasies. Tech Coloproctol 2016; 21:15-23. [PMID: 27928687 DOI: 10.1007/s10151-016-1555-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023]
Abstract
In rectal cancer patients, the stage of the disease, local spread and distant metastases status drive the treatment decisions to be made. Histopathology remains the gold standard, but preoperative staging, particularly magnetic resonance imaging (MRI), is pivotal for defining surgical planes and finding patients who could potentially benefit from preoperative regimes. Unfortunately, due to a lack of awareness, expertise and practise the quality of rectal cancer MRI and histopathology reporting varies among centres. This paper highlights the most important and frequently occurring radiological and histopathological discrepancies/mistakes to be aware of.
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Affiliation(s)
- S Balyasnikova
- Department of Radiology, The Royal Marsden NHS Foundation Trust, Sutton, UK.,Department of Radiology, The Royal Marsden NHS Foundation Trust, Fulham, UK.,Imperial College London, London, UK
| | - N Haboubi
- Department of Histopathology, Spire Hospital Healthcare Trust, Russell Road, Whalley Range, Manchester, M16 8AJ, UK.
| | - B Moran
- Department of Colorectal Surgery, North Hampshire Hospital, Basingstoke, UK
| | - G Brown
- Department of Radiology, The Royal Marsden NHS Foundation Trust, Sutton, UK.,Department of Radiology, The Royal Marsden NHS Foundation Trust, Fulham, UK.,Imperial College London, London, UK
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