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Yeo D, Seyfi D, Bastian A, Strauss H, Leach A, Klemm V, Pirrello A, Spring K, Saxena P, Wahlroos S, Sutherland S, Grimison P, Park JS, Sandroussi C, Rasko JE. Portal venous circulating tumor cells as a biomarker for relapse prediction in resected pancreatic cancer. Cell Mol Life Sci 2025; 82:155. [PMID: 40208273 PMCID: PMC11985722 DOI: 10.1007/s00018-025-05669-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 03/16/2025] [Accepted: 03/19/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Pancreatic cancer is an aggressive disease with poor prognosis. The only potentially curative treatment option is surgical resection, however recurrence is common. Biomarkers to detect minimal residual disease, assist with risk stratification, relapse and real time monitoring, are required. Circulating tumor cells (CTCs) are a promising liquid biopsy biomarker for solid tumors. However, their role in monitoring minimal residual disease in pancreatic cancer remains to be determined. Our study aimed to investigate whether detection and enumeration of CTCs could predict recurrence and provide monitoring of disease status. METHOD Participants planned for Whipple procedure or partial pancreatectomy were enrolled in this prospective pilot study. Intraoperatively, 7.5 mL of portal and peripheral venous blood were collected, and peripheral venous blood was also collected post-surgery. CTC identification and enumeration were performed using the AccuCyte-CyteFinder platform and CellSieve microfiltration. RESULTS Of 29 participants, 20 were confirmed to have epithelial cancer by histopathology, where 15 had pancreatic ductal adenocarcinoma. In those with epithelial cancer, CTCs were detected intraoperatively in 75% of portal venous blood samples, in contrast to 40% detected in peripheral venous blood (median: 6 and 0 per 7.5mL respectively). Only portal venous CTC detection was predictive of pancreatic ductal adenocarcinoma relapse. The positive (> 5) portal venous CTC group had a 6.67 times higher risk of recurring (odds ratio = 20.43, sensitivity = 1.00, specificity = 0.625). Detection of peripheral venous CTCs post-surgery was also correlated with relapse in a small subset of patients. CONCLUSIONS If validated, CTCs may provide a prognostic and monitoring biomarker in patients with pancreatic cancer undergoing surgery.
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Affiliation(s)
- Dannel Yeo
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
| | - Doruk Seyfi
- Department of Hepatobiliary and Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
- Upper Gastrointestinal Surgery, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Althea Bastian
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
| | - Heidi Strauss
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
| | - Anna Leach
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
| | - Vera Klemm
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
| | - Anthony Pirrello
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
| | - Kevin Spring
- Medical Oncology Group, Liverpool Clinical School, School of Medicine, Western Sydney University and Ingham Institute for Applied Medical Research, Liverpool, Australia
- Concord Institute of Academic Surgery, Sydney Local Health District, Concord, Australia
- South-West Sydney Clinical Campuses, UNSW Medicine & Health, Sydney, Australia
| | - Payal Saxena
- Division of Gastroenterology, Department of Medicine, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
- Gastroenterology, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Sara Wahlroos
- Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Sarah Sutherland
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Peter Grimison
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Jin-Soo Park
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Department of Hepatobiliary and Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
- Upper Gastrointestinal Surgery, Chris O'Brien Lifehouse, Camperdown, Australia
| | - Charbel Sandroussi
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia
- Department of Hepatobiliary and Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia
- Upper Gastrointestinal Surgery, Chris O'Brien Lifehouse, Camperdown, Australia
| | - John Ej Rasko
- Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia.
- Precision Oncology Laboratory, Cancer Innovations, Centenary Institute, Camperdown, Australia.
- Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.
- Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia.
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Tang J, Li X, Tang N, Lin X, Du Y, Zhang S, Li Q, Zhang Y, Zhang Y, Hang H, Qiu T, Qiu Y, Cheng H, Dai Z, Hong H, Wei W, He J, Yan C. CD44 identified as a diagnostic biomarker for highly malignant CA19-9 negative pancreatic cancer. Cancer Lett 2025; 622:217713. [PMID: 40216152 DOI: 10.1016/j.canlet.2025.217713] [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: 02/26/2025] [Revised: 03/25/2025] [Accepted: 04/08/2025] [Indexed: 04/16/2025]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited diagnostic biomarkers. Carbohydrate antigen 19-9 (CA19-9) is a widely used clinical biomarker and is generally considered to correlate with PDAC malignancy. However, the relationship between CA19-9 expression levels and tumor aggressiveness remains underexplored. In this study, we report a biphasic relationship between CA19-9 expression levels and PDAC malignancy, where both negative (<5 U/mL) and high (>37 U/mL) CA19-9 levels are associated with increased tumor aggressiveness. We defined CA19-9 negative PDAC as tumors that lack CA19-9 expression intracellulary, on the cell membrane, and in secreted form. In PDAC cell lines and patient-derived organoids, CA19-9 negativity, confirmed by immunofluorescence, flow cytometry and ELISA, correlated with more aggressive behaviors. In PDAC patients, tumors from those with serum CA19-9 levels below 5 U/mL exhibited stronger metabolically activity, more immunosuppressive tumor microenvironment, and worse survival than CA19-9 positive tumors, with over 90 % showing absent CA19-9 expression by immunohistochemistry (IHC). Glycoproteomics profiling identified CD44 as a highly expressed biomarker in CA19-9 negative PDAC. Elevated CD44 expression effectively distinguished CA19-9 negative PDAC from both CA19-9 positive PDAC and CA19-9 negative benign pancreatic diseases, suggesting its potential as a diagnostic tool. Furthermore, we developed a radionuclide-labeled CD44 antibody 89Zr-1M2E3, which specifically recognized CA19-9 negative PDAC tumors in preclinical models using PET-CT imaging. These findings highlight CD44 as a promising biomarker and therapeutic target for diagnosing and treating CA19-9 negative PDAC.
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Affiliation(s)
- Jiatong Tang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China; Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, Jiangsu Province, China
| | - Xiaoyang Li
- Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Neng Tang
- Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Xiawen Lin
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yixiang Du
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China
| | - Shuo Zhang
- Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Qi Li
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yifan Zhang
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yixuan Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China; Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, Jiangsu Province, China
| | - Hexing Hang
- Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Tongtong Qiu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China; Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yudong Qiu
- Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Institute of Pancreatology, Nanjing University, Nanjing, Jiangsu Province, China
| | - Hao Cheng
- Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Zhan Dai
- Nanjing Okay Biotechnology Co., Ltd, Nanjing, Jiangsu Provinve, China
| | - Hao Hong
- Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu Province, China
| | - Wei Wei
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China; Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, Jiangsu Province, China.
| | - Jian He
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Institute of Pancreatology, Nanjing University, Nanjing, Jiangsu Province, China.
| | - Chao Yan
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu Province, China; Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing, Jiangsu Province, China; Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China; Institute of Pancreatology, Nanjing University, Nanjing, Jiangsu Province, China.
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Ahmadipour M, Bhattacharya A, Sarafbidabad M, Syuhada Sazali E, Krishna Ghoshal S, Satgunam M, Singh R, Rezaei Ardani M, Missaoui N, Kahri H, Pal U, Ling Pang A. CA19-9 and CEA biosensors in pancreatic cancer. Clin Chim Acta 2024; 554:117788. [PMID: 38246211 DOI: 10.1016/j.cca.2024.117788] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 01/15/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024]
Abstract
Cancer is a complex pathophysiological condition causing millions of deaths each year. Early diagnosis is essential especially for pancreatic cancer. Existing diagnostic tools rely on circulating biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA). Unfortunately, these markers are nonspecific and may be increased in a variety of disorders. Accordingly, diagnosis of pancreatic cancer generally involves more invasive approaches such as biopsy as well as imaging studies. Recent advances in biosensor technology have allowed the development of precise diagnostic tools having enhanced analytical sensitivity and specificity. Herein we examine these advances in the detection of cancer in general and in pancreatic cancer specifically. Furthermore, we highlight novel technologies in the measurement of CA19-9 and CEA and explore their future application in the early detection of pancreatic cancer.
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Affiliation(s)
- Mohsen Ahmadipour
- Institute of Power Engineering, Universiti Tenaga Nasional, 43650 Serdang, Selangor, Malaysia.
| | - Anish Bhattacharya
- Advanced Optical Materials Research Group, Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia; Ibnu Sina Institute of Laser Centre, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia
| | - Mohsen Sarafbidabad
- Biomedical Engineering Department, Faculty of Engineering, University of Isfahan, Isfahan, Iran
| | - Ezza Syuhada Sazali
- Advanced Optical Materials Research Group, Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia; Ibnu Sina Institute of Laser Centre, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia
| | - Sib Krishna Ghoshal
- Advanced Optical Materials Research Group, Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia; Ibnu Sina Institute of Laser Centre, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia
| | - Meenaloshini Satgunam
- Institute of Power Engineering, Universiti Tenaga Nasional, 43650 Serdang, Selangor, Malaysia; Department of Mechanical Engineering, Universiti Tenaga Nasional, 43650 Serdang, Selangor, Malaysia
| | - Ramesh Singh
- Institute of Power Engineering, Universiti Tenaga Nasional, 43650 Serdang, Selangor, Malaysia; Center of Advanced Manufacturing and Materials Processing (AMMP), Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Mohammad Rezaei Ardani
- School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Engineering Campus, 14300 Nibong Tebal, Pulau Pinang, Malaysia
| | - Nadhem Missaoui
- Laboratory of Interfaces and Advanced Materials, Faculty of Sciences, University of Monastir, Monastir, Tunisia
| | - Hamza Kahri
- Laboratory of Interfaces and Advanced Materials, Faculty of Sciences, University of Monastir, Monastir, Tunisia
| | - Ujjwal Pal
- Department of Analytical and Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, India
| | - Ai Ling Pang
- Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, 31900 Kampar, Perak, Malaysia
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Rahmani H, Mansouri Majd S, Salimi A, Ghasemi F. Ultrasensitive immunosensor for monitoring of CA 19-9 pancreatic cancer marker using electrolyte-gated TiS 3 nanoribbons field-effect transistor. Talanta 2023; 257:124336. [PMID: 36863296 DOI: 10.1016/j.talanta.2023.124336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 02/04/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023]
Abstract
Measuring CA 19-9 antigen level is critical for early diagnosis of pancreatic cancer, monitoring the treatment process, and predicting disease recurrence. The purpose of this research is to assess the application of novel few-layered TiS3 nanoribbons material as a channel material in electrolyte-gated field-effect transistor immunosensor for rapid detection of CA 19-9 antigen as a cancer marker. Accordingly, TiS3 nanoribbons were produced through liquid-phase exfoliation of as-synthesized TiS3 whiskers in N, N-dimethylformamide. Then, dispersed TiS3 nanoribbons were drop cast onto the FET surface to form an active channel material between source and drain electrodes. Subsequently, the channel surface was modified by utilizing 1-naphthylamine (NA) and glutaraldehyde (GA) to strengthen the binding of monoclonal antibody 19-9 to TiS3 nanoribbons. Spectroscopic and microscopic methods were utilized for comprehensive characterizations. Electrical characterization of electrolyte-gated TiS3 nanoribbons field-effect transistor represented a depletion-mode n-type behavior with field-effect mobility of 0.059 cm2/Vs, current on/off ratio of 10.88 and subthreshold swing (SS) of 450.9 mV/decade. With increasing in CA 19-9 antigen concentration from 1.0 × 10-12 U/mL to 1.0 × 10-5 U/mL, a decrease in the drain current occurred with high sensitivity of 0.04 μA/decade and a detection limit of 1.3 × 10-13 U/mL. Additionally, the proposed TiS3 nanoribbons FET immunosensor exhibited outstanding selectivity, and its good performance was compared with an enzyme-linked immunosorbent assay (ELISA) for spiked real human serum samples. The good and satisfactory obtained results of the proposed immunosensor suggest that the developed platform can be a superb candidate for cancer diagnosis and therapeutic monitoring.
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Affiliation(s)
- Hedyeh Rahmani
- Department of Chemistry, University of Kurdistan, 66177-15175, Sanandaj, Iran
| | | | - Abdollah Salimi
- Department of Chemistry, University of Kurdistan, 66177-15175, Sanandaj, Iran; Research Center for Nanotechnology, University of Kurdistan, 66177-15175, Sanandaj, Iran.
| | - Foad Ghasemi
- Nanoscale Physics Device Lab (NPDL), Department of Physics, University of Kurdistan, 66177-15175, Sanandaj, Iran
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Gao C, Fan Z, Yang J, Shi M, Li Y, Zhan H. Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms. Pancreatology 2023; 23:204-212. [PMID: 36710224 DOI: 10.1016/j.pan.2023.01.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 01/09/2023] [Accepted: 01/16/2023] [Indexed: 01/31/2023]
Abstract
OBJECTIVES High-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs. METHODS Seventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan-Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses. RESULTS Serum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs. CONCLUSIONS Serum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.
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Affiliation(s)
- Changhao Gao
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Ming Shi
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Yongzheng Li
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
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Watanabe F, Suzuki K, Noda H, Rikiyama T. Liquid biopsy leads to a paradigm shift in the treatment of pancreatic cancer. World J Gastroenterol 2022; 28:6478-6496. [PMID: 36569270 PMCID: PMC9782840 DOI: 10.3748/wjg.v28.i46.6478] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/25/2022] [Accepted: 11/21/2022] [Indexed: 12/08/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most cancers. Its 5-year survival rate is very low. The recent induction of neoadjuvant chemotherapy and improvements in chemotherapy for patients with pancreatic cancer have resulted in improved survival outcomes. However, the prognosis of pancreatic cancer is still poor. To dramatically improve the prognosis, we need to develop more tools for early diagnosis, treatment selection, disease monitoring, and response rate evaluation. Recently, liquid biopsy (circulating free DNA, circulating tumor DNA, circulating tumor cells, exosomes, and microRNAs) has caught the attention of many researchers as a new biomarker that is minimally invasive, confers low-risk, and displays an overall state of the tumor. Thus, liquid biopsy does not employ the traditional difficulties of obtaining tumor samples from patients with advanced PDAC to investigate their molecular biological status. In addition, it allows for long-term monitoring of the molecular profile of tumor progression. These could help in identifying tumor-specific alterations that use the target structure for tailor-made therapy. Through this review, we highlighted the latest discoveries and advances in liquid biopsy technology in pancreatic cancer research and showed how it can be applied in clinical practice.
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Affiliation(s)
- Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
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Coppola A, Farolfi T, La Vaccara V, Cammarata R, Caputo D. Role of Neoplastic Markers in Pancreatic Adenocarcinoma. J Clin Med 2022; 11:6509. [PMID: 36362735 PMCID: PMC9653570 DOI: 10.3390/jcm11216509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 11/01/2022] [Indexed: 01/27/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the "Big Five" lethal cancers, which include lung, bowel, breast and prostate cancer [...].
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Affiliation(s)
| | - Tommaso Farolfi
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Vincenzo La Vaccara
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Roberto Cammarata
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Damiano Caputo
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
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Ross PJ, Wasan HS, Croagh D, Nikfarjam M, Nguyen N, Aghmesheh M, Nagrial AM, Bartholomeusz D, Hendlisz A, Ajithkumar T, Iwuji C, Wilson NE, Turner DM, James DC, Young E, Harris MT. Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy. ESMO Open 2022; 7:100356. [PMID: 34953400 PMCID: PMC8717429 DOI: 10.1016/j.esmoop.2021.100356] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.
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Affiliation(s)
- P J Ross
- Guy's & St Thomas' Hospital NHS Foundation Trust, London, UK.
| | - H S Wasan
- Imperial College Healthcare NHS Trust, London, UK
| | - D Croagh
- Monash Health, Clayton, Australia
| | - M Nikfarjam
- Austin Hospital, University of Melbourne, Australia
| | - N Nguyen
- Royal Adelaide Hospital, Adelaide, Australia
| | - M Aghmesheh
- Southern Medical Day Care Centre, Wollongong, Australia
| | - A M Nagrial
- The Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia
| | | | - A Hendlisz
- Institut Jules Bordet, Brussels, Belgium
| | - T Ajithkumar
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - C Iwuji
- Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - N E Wilson
- OncoSil Medical Limited, Sydney, Australia
| | - D M Turner
- OncoSil Medical Limited, Sydney, Australia
| | - D C James
- OncoSil Medical Limited, Sydney, Australia
| | - E Young
- Southern Star Research Pty Ltd, Gordon, Australia
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9
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Watanabe F, Suzuki K, Tamaki S, Abe I, Endo Y, Takayama Y, Ishikawa H, Kakizawa N, Saito M, Futsuhara K, Noda H, Konishi F, Rikiyama T. Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients. Sci Rep 2021; 11:20797. [PMID: 34675229 PMCID: PMC8531317 DOI: 10.1038/s41598-021-00060-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.
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Affiliation(s)
- Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan.
| | - Sawako Tamaki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Iku Abe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Yuhei Endo
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Yuji Takayama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Hideki Ishikawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Nao Kakizawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Masaaki Saito
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Kazushige Futsuhara
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Fumio Konishi
- Nerima Hikarigaoka Hospital, 2-11-1, Hikarigaoka, Nerima-ku, Tokyo, 179-0072, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
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10
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Lyu SC, Wang J, Huang M, Wang HX, Zhou L, He Q, Lang R. CA19-9 Level to Serum γ-Glutamyltransferase as a Potential Prognostic Biomarker in Patients with Pancreatic Head Carcinoma. Cancer Manag Res 2021; 13:4887-4898. [PMID: 34188542 PMCID: PMC8232842 DOI: 10.2147/cmar.s313517] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/19/2021] [Indexed: 12/19/2022] Open
Abstract
Background The aim of this study was to reduce the influence of biliary obstruction on carbohydrate antigen 19-9 level (CA19-9) by introducing the CA19-9 level to serum γ-glutamyltransferase (GGT) ratio as an indicator, and ultimately to reveal the correlation between CA19-9/GGT and the prognosis of patients with pancreatic head carcinoma (PHC). Methods A total of 339 enrolled patients who underwent pancreatoduodenectomy for PHC in Beijing ChaoYang Hospital from January 2010 to December 2019 were analyzed retrospectively. The optimal cut-off value, according to which patients were divided into a low-ratio group (Group 1, n=179) and a high-ratio group (Group 2, n=160), was determined by the ROC curve obtained from preoperative CA19-9/GGT and 1-year survival. Through univariate and multivariate analyses, risk factors for postoperative tumor recurrence and long-term survival were screened out among PHC patients. Results The best cut-off value of CA19-9/GGT was 2.07 (area under the curve=0.567, 95% CI 0.498-0.636). Compared with Group 2, Group 1 had lower CA19-9, and higher GGT, total bilirubin (TB) and lymph-node metastasis rate (P<0.05). The 1-, 2- and 3-year disease-free survival rates of patients in Groups 1 and 2 were 68.2%, 42.5% and 28.2%, and 42.2%, 19.3% and 18.3%, respectively (P=0.000), and the 1-, 2- and 3-year overall survival rates were 79.1%, 50.7% and 29.1%, and 56.7%, 22.2% and 17.2%, respectively (P=0.000). Multivariate analysis showed that CA19-9/GGT, portal system invasion and lymph-node metastasis were independent risk factors for postoperative tumor recurrence and long-term survival among patients with PHC. Conclusion Compared with CA19-9 level alone, CA19-9/GGT plays a more precise role in the evaluation of postoperative tumor recurrence and the long-term prognosis of PHC patients. The lower the ratio, the better the long-term prognosis. The CA19-9/GGT ratio may prove to be a useful biomarker for identifying PHC patients at high risk of early recurrence and unfavorable prognosis.
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Affiliation(s)
- Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Jing Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Mengxiu Huang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Han-Xuan Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China
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11
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Coppola A, La Vaccara V, Fiore M, Farolfi T, Ramella S, Angeletti S, Coppola R, Caputo D. CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis. Front Oncol 2021; 11:690580. [PMID: 34123859 PMCID: PMC8190389 DOI: 10.3389/fonc.2021.690580] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022] Open
Abstract
Background The choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC. Methods Preoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction. Results Increased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p <0.001). This ability, confirmed in all the series by ROC curve analysis (Ca 19.9 ≥32 U/ml), was lost in the presence of hypoalbuminemia. Furthermore, Ca 19.9 at the cut off >418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059). Conclusions In R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.
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Affiliation(s)
| | | | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Tommaso Farolfi
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
| | - Sara Ramella
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, Campus Bio-Medico University, Rome, Italy
| | - Roberto Coppola
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
| | - Damiano Caputo
- Department of Surgery, Campus Bio-Medico University, Rome, Italy
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12
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Luo G, Jin K, Deng S, Cheng H, Fan Z, Gong Y, Qian Y, Huang Q, Ni Q, Liu C, Yu X. Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. Biochim Biophys Acta Rev Cancer 2021; 1875:188409. [PMID: 32827580 DOI: 10.1016/j.bbcan.2020.188409] [Citation(s) in RCA: 177] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/29/2020] [Accepted: 07/20/2020] [Indexed: 02/07/2023]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.
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Affiliation(s)
- Guopei Luo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Shengming Deng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - He Cheng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Zhiyao Fan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Yitao Gong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Yunzhen Qian
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Qiuyi Huang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, China; Department of Oncology, Shanghai Medical College, Fudan University, China; Pancreatic Cancer Institute, Fudan University, Shanghai Pancreatic Cancer Institute, China.
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13
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Di Fiore F, Bouché O, Lepage C, Sefrioui D, Gangloff A, Schwarz L, Tuech JJ, Aparicio T, Lecomte T, Boulagnon-Rombi C, Lièvre A, Manfredi S, Phelip JM, Michel P. COVID-19 epidemic: Proposed alternatives in the management of digestive cancers: A French intergroup clinical point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig Liver Dis 2020; 52:597-603. [PMID: 32418773 PMCID: PMC7255323 DOI: 10.1016/j.dld.2020.03.031] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 03/29/2020] [Accepted: 03/30/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients treated for malignancy are considered at risk of severe COVID-19. This exceptional pandemic has affected countries on every level, particularly health systems which are experiencing saturation. Like many countries, France is currently greatly exposed, and a complete reorganization of hospitals is ongoing. We propose here adaptations of diagnostic procedures, therapies and care strategies for patients treated for digestive cancer during the COVID-19 epidemic. METHODS French societies of gastroenterology and gastrointestinal (GI) oncology carried out this study to answer two main questions that have arisen (i) how can we limit high-risk situations for GI-cancer patients and (ii) how can we limit contact between patients and care centers to decrease patients' risk of contamination while continuing to treat their cancer. All recommendations are graded as experts' agreement according to the level of evidence found in the literature until March 2020. RESULTS A proposal to adapt treatment strategies was made for the main GI oncology situations. Considering the level of evidence and the heterogeneous progression of the COVID-19 epidemic, all proposals need to be considered by a multidisciplinary team and implemented with patient consent. CONCLUSION COVID-19 epidemic may significantly affect patients treated for digestive malignancies. Healthcare teams need to consider adapting treatment sequences when feasible and according to the epidemic situation.
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Affiliation(s)
- Frederic Di Fiore
- Department of Hepatogastroenterology, Normandie Université, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, F 76000 Rouen, France.
| | - Olivier Bouché
- Digestive Oncology, CHU Reims, University Reims Champagne Ardennes, France
| | - Come Lepage
- Hepato-Gastroenterology Department, University Hospital Le Bocage, EPICAD INSERM LNC-UMR 1231, Université de Bourgogne et Franche Comté, Dijon, France
| | - David Sefrioui
- Department of Hepatogastroenterology, Normandie Université, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, F 76000 Rouen, France
| | - Alice Gangloff
- Department of Hepatogastroenterology, Normandie Université, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, F 76000 Rouen, France
| | - Lilian Schwarz
- Department of Digestive Surgery, Normandie Université, UNIROUEN, Inserm U1245, IRON group, F 76000 Rouen, France
| | - Jean Jacques Tuech
- Department of Digestive Surgery, Normandie Université, UNIROUEN, Inserm U1245, IRON group, F 76000 Rouen, France
| | - Thomas Aparicio
- Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris, Paris, France
| | - Thierry Lecomte
- Gastroenterology and Endoscopy Department, Trousseau Hospital, University F Rabelais Tours, France
| | | | - Astrid Lièvre
- Rennes 1 University, Rennes, France; Association pour le Dépistage des Cancers en Ille-et-Vilaine, ADECI35, Rennes, France; Department of Gastroenterology, CHU Pontchaillou, Rennes, France; INSERM UMR 1242, COSS "Chemistry, Oncogenesis, Stress Signaling", Rennes, France
| | - Sylvain Manfredi
- Hepato-Gastroenterology Department, University Hospital Le Bocage, EPICAD INSERM LNC-UMR 1231, Université de Bourgogne et Franche Comté, Dijon, France
| | - Jean Marc Phelip
- Department of Gastroenterology and Digestive Oncology, University Hospital of Saint Etienne, Saint Etienne, France
| | - Pierre Michel
- Department of Hepatogastroenterology, Normandie Université, UNIROUEN, Inserm U1245, IRON group, Rouen University Hospital, F 76000 Rouen, France.
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Abstract
CA19-9 values are regularly measured in patients with pancreatic cancer. Certainly, its potential as a biomarker has been compromised by false negative results in CA19-9 negative patients and false positive results in benign pancreatico-biliary diseases. For detection of PDAC recurrence, however, CA19-9 might play an important role. The aim of this study is to analyze the accuracy of CA19-9 for detecting recurrence of pancreatic cancer. All included patients were treated either at the University Medical Center Goettingen, or at the Department of Interdisciplinary Oncology and Pneumonology, DRK-Kliniken Nordhessen, Kassel. We analyzed data of 93 patients with pancreatic cancer in the training set and 41 in the validation set, both retrospectively. Pre- and postoperative CA19-9 values and results of imaging techniques were compared. We performed ROC-analysis. The association between longitudinally measured CA19-9 values and relapse was studied with a joint model between a random effects model for the longitudinal CA19-9 measurements and a Cox proportional hazards models for the survival data. In the test set (n = 93 patients) the median follow-up time was 644 days (22 months). Overall, 71 patients (76.3%) developed recurrence during follow-up. Patients with CA19-9 values of <10kU/l were considered as CA19-9 negative patients (n = 11) and excluded from further analysis. Among the rest, approximately 60% of the patients showed significantly elevated CA19-9 prior to detection of recurrence by imaging techniques. Recurrence was shown by 2.45 times elevated CA19-9 values with 90% positive predictive value. In the validation set, 2.45 times elevated CA19-9 values showed recurrence with 90% sensitivity and 83,33% specificity, with an area under the curve of 95%. Based on measured CA19-9 values during follow-up care, the joint model estimates in recurrence-free patients the probability of recurrence-free survival. CA19-9 elevation is an early and reliable sign for PDAC recurrence. On the strength of a very high accuracy in CA19-9 positive patients, it should be considered to use CA19-9 for therapy decision even without a correlate of imaging technics. Using the joint model, follow-up care of PDAC patients after curative therapy can be stratified.
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