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Ruze R, Chen Y, Xu R, Song J, Yin X, Wang C, Xu Q. Obesity, diabetes mellitus, and pancreatic carcinogenesis: Correlations, prevention, and diagnostic implications. Biochim Biophys Acta Rev Cancer 2023; 1878:188844. [PMID: 36464199 DOI: 10.1016/j.bbcan.2022.188844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/13/2022] [Accepted: 11/26/2022] [Indexed: 12/03/2022]
Abstract
The prevalence of obesity, diabetes mellitus (DM), and pancreatic cancer (PC) has been consistently increasing in the last two decades worldwide. Sharing various influential risk factors in genetics and environmental inducers in pathogenesis, the close correlations of these three diseases have been demonstrated in plenty of clinical studies using multiple parameters among different populations. On the contrary, most measures aimed to manage and treat obesity and DM effectively reduce the risk and prevent PC occurrence, yet certain drugs can inversely promote pancreatic carcinogenesis instead. Most importantly, an elevation of blood glucose with or without a reduction in body weight, along with other potential tools, may provide valuable clues for detecting PC at an early stage in patients with obesity and DM, favoring a timely intervention and prolonging survival. Herein, the epidemiological and etiological correlations among these three diseases and the supporting clinical evidence of their connections are first summarized to favor a better and more thorough understanding of obesity- and DM-related pancreatic carcinogenesis. After comparing the distinct impacts of different weight-lowering and anti-diabetic treatments on the risk of PC, the possible diagnostic implications of hyperglycemia and weight loss in PC screening are also addressed in detail.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Yuan Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Jianlu Song
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Xinpeng Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Chengcheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China.
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China.
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Taguchi M, Bouchi R, Fukuda T, Ihana-Sugiyama N, Kodani N, Ohsugi M, Tanabe A, Ueki K, Kajio H. Clinical significance of tumor markers in patients with type 2 diabetes: a retrospective observational study. Diabetol Int 2023; 14:40-50. [PMID: 36636164 PMCID: PMC9829951 DOI: 10.1007/s13340-022-00594-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/24/2022] [Indexed: 01/16/2023]
Abstract
Aim To cross-sectionally and longitudinally investigate the association between tumor markers (Cancer embryonic antigen (CEA) Carbohydrate antigen 19-9 (CA19-9)) and malignancies in type 2 diabetes patients without evidence of malignancy. Materials and Methods The study included 707 patients admitted for the treatment of diabetes from 1 August 2010 to 1 September 2018. Serum CEA and CA19-9 levels were measured for screening of malignancies at admission. Abdominal ultrasonography, computed tomography, and endoscopy were performed for close examination. The percentage of patients diagnosed with malignancy was calculated, and among those without malignancy, the incidence of malignancies was examined after discharge. Results A total of 26 patients (3.7%) were newly diagnosed with malignancy during hospitalization. The optimal cut-off value of CEA and CA19-9 by receiver operating characteristic analysis was 5.0 ng/mL and 75 U/mL, and their positive predictive values (PPV) were 8.7% and 22.5%, respectively. The addition of CA19-9 to age, smoking status, body mass index, and glycated hemoglobin significantly improved classification performance for malignancy using net reclassification improvement (0.682, 95% CI 0.256-1.107) and integrated discrimination improvement (0.150, 95% CI 0.007-0.294). Among 681 patients without malignancies during hospitalization, 30 patients (4.4%) developed malignancies during an average follow-up of 3.9 years. CA19-9 (hazard ratio: 1.005, 95% CI: 1.003-1.008) was associated with the development of malignancies. Conclusions PPV of serum CEA and CA19-9 for detecting malignancy was high in type 2 diabetes patients with poor glycemic control. Measuring CA19-9 was found to be valuable to cross-sectionally and longitudinally detect malignancies. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-022-00594-x.
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Affiliation(s)
- Maho Taguchi
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Ryotaro Bouchi
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
- Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Tatsuya Fukuda
- Department of Endocrinology and Metabolism, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, 2-44-1 Kabuki-cho, Shinjuku-ku, Tokyo, 160-8488 Japan
| | - Noriko Ihana-Sugiyama
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
- Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Noriko Kodani
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Mitsuru Ohsugi
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
- Diabetes and Metabolism Information Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Akiyo Tanabe
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Kohjiro Ueki
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
- Diabetes Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
| | - Hiroshi Kajio
- Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan
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Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:891-904. [PMID: 35913776 DOI: 10.1097/meg.0000000000002415] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker for detecting pancreatic cancer (PC). Since early diagnosis is important for improving PC prognosis, a comprehensive understanding of the diagnostic performance of CA19-9 is critical. This study focused on comprehensive evaluation of the efficacy of CA19-9 in PC diagnosis. Literature research was based on the seven databases. Studies released from January 2002 to January 2022 focused on the efficacy of CA19-9 in the detection of PC were included. Summarized sensitivity, specificity, and sROC/accuracy of discrimination (AUC) were estimated. Potential publication bias was measured with Funnel plot and Egger's test. Meta-regression was performed to detect possible causes of heterogeneity. Subgroup analysis was used to assess the diagnostic efficacy of CA19-9 under different conditions. The study is registered on PROSPERO (CRD42021253861). Seventy-nine studies containing 20 991 participants who met the criteria were included. The pooled sensitivity, specificity, and AUC of CA19-9 in diagnose PC were 72% (95% CI, 71-73%), 86% (95% CI, 85-86%), and 0.8474 (95% CI, 0.8272-0.8676). Subgroup analysis suggested that the diagnostic efficiency of CA19-9 in studies with healthy controls was the highest, followed by intraductal papillary mucinous neoplasm, in pancreatitis and diabetes were consistent with the overall result. Our analysis showed that serum CA19-9 had high and stable diagnostic efficacy for PC (not affected by diabetes). Subgroup analysis showed that serum CA19-9 yielded highest effectiveness in the diagnosis of pancreatic precancerous lesions, which indicated an irreplaceable clinical value in the early detection and warning value for PC.
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Affiliation(s)
- Boqiang Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- The First School of Clinical Medicine, Xi'an, China
| | - Boyue Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| | - Fangyao Chen
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
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Balaban DV, Marin FS, Manucu G, Zoican A, Ciochina M, Mina V, Patoni C, Vladut C, Bucurica S, Costache RS, Ionita-Radu F, Jinga M. Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer. World J Clin Oncol 2022; 13:630-640. [PMID: 36157158 PMCID: PMC9346420 DOI: 10.5306/wjco.v13.i7.630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/19/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of death from cancer worldwide. Tumor markers like carbohydrate antigen 19-9 (CA 19-9) have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy. AIM To delineate the phenotype of normal CA 19-9 PDAC according to clinical features, disease staging and prognosis as compared with high CA 19-9 PDAC cases. METHODS We performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition. Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL. We performed a comparison between the two groups with regard to demographic and clinical data, biomarkers, tumor staging and 6-mo survival. RESULTS Altogether 111 patients were recruited with 29 having documented normal CA 19-9 (< 37 U/mL). In the CA 19-9 negative group of patients, 20.68% had elevated levels of both CEA and CA 125, 13.79% for CA 125 only whilst 17.24% for CEA only. The two groups had similar demographic characteristics. Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases (76.83% vs 55.17%), while smoking was slightly more prevalent in the latter group (28.04% vs 31.03%). Tumors over 2 cm were more frequently seen in the positive CA 19-9 group, reflecting a higher proportion of locally advanced and metastatic neoplasia (87.7% vs 79.3%). Six-month survival was higher for the negative CA 19-9 group (58.62% vs 47.56%). CONCLUSION Elevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology, high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases. CEA and CA 125 can be adjunctive useful markers for PDAC, especially in CA 19-9 negative cases.
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Affiliation(s)
- Daniel Vasile Balaban
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Flavius Stefan Marin
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
- Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, Paris 75014, France
| | - George Manucu
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Andreea Zoican
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Marina Ciochina
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Victor Mina
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Cristina Patoni
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Catalina Vladut
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Prof Dr. Agrippa Ionescu Clinical Emergency Hospital, Bucharest 020021, Romania
| | - Sandica Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Raluca Simona Costache
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Florentina Ionita-Radu
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
| | - Mariana Jinga
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest 020021, Romania
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Oldfield L, Evans A, Rao RG, Jenkinson C, Purewal T, Psarelli EE, Menon U, Timms JF, Pereira SP, Ghaneh P, Greenhalf W, Halloran C, Costello E. Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes. EBioMedicine 2022; 75:103802. [PMID: 34990893 PMCID: PMC8741427 DOI: 10.1016/j.ebiom.2021.103802] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.
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Affiliation(s)
- Lucy Oldfield
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Anthony Evans
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Rohith Gopala Rao
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Claire Jenkinson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Tejpal Purewal
- Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, UK
| | - Eftychia E Psarelli
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Usha Menon
- Institute of Clinical Trials and Methodology, University College London, UK
| | - John F Timms
- Women's Cancer, Institute for Women's Health, University College London, UK
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London, UK
| | - Paula Ghaneh
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - William Greenhalf
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Christopher Halloran
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
| | - Eithne Costello
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK.
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Tabang DN, Cui Y, Tremmel DM, Ford M, Li Z, Sackett SD, Odorico JS, Li L. Analysis of pancreatic extracellular matrix protein post-translational modifications via electrostatic repulsion-hydrophilic interaction chromatography coupled with mass spectrometry. Mol Omics 2021; 17:652-664. [PMID: 34318855 PMCID: PMC8511275 DOI: 10.1039/d1mo00104c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The pancreas is a vital organ with digestive and endocrine roles, and diseases of the pancreas affect millions of people yearly. A better understanding of the pancreas proteome and its dynamic post-translational modifications (PTMs) is necessary to engineer higher fidelity tissue analogues for use in transplantation. The extracellular matrix (ECM) has major roles in binding and signaling essential to the viability of insulin-producing islets of Langerhans. To characterize PTMs in the pancreas, native and decellularized tissues from four donors were analyzed. N-Glycosylated and phosphorylated peptides were simultaneously enriched via electrostatic repulsion-hydrophilic interaction chromatography and analyzed with mass spectrometry, maximizing PTM information from one workflow. A modified surfactant and chaotropic agent assisted sequential extraction/on-pellet digestion was used to maximize solubility of the ECM. The analysis resulted in the confident identification of 3650 proteins, including 517 N-glycoproteins and 148 phosphoproteins. We identified 214 ECM proteins, of which 99 were N-glycosylated, 18 were phosphorylated, and 9 were found to have both modifications. Collagens, a major component of the ECM, were the most highly glycosylated of the ECM proteins and several were also heavily phosphorylated, raising the possibility of structural and thus functional changes resulting from these modifications. To our knowledge, this work represents the first characterization of PTMs in pancreatic ECM proteins. This work provides a basal profile of PTMs in the healthy human pancreatic ECM, laying the foundation for future investigations to determine disease-specific changes such as in diabetes and pancreatic cancer, and potentially helping to guide the development of tissue replacement constructs. Data are available via ProteomeXchange with identifier PXD025048.
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Affiliation(s)
- Dylan Nicholas Tabang
- Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI, 53706, USA.
| | - Yusi Cui
- Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI, 53706, USA.
| | - Daniel M Tremmel
- Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Megan Ford
- Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Zihui Li
- Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI, 53706, USA.
| | - Sara Dutton Sackett
- Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Jon S Odorico
- Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Lingjun Li
- Department of Chemistry, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI, 53706, USA.
- School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA
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Duan X, Wang W, Pan Q, Guo L. Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development. Front Oncol 2021; 11:730038. [PMID: 34485159 PMCID: PMC8415500 DOI: 10.3389/fonc.2021.730038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 07/30/2021] [Indexed: 12/12/2022] Open
Abstract
The relationship between type 2 diabetes mellitus (T2DM) and pancreatic cancer (PC) is complex. Diabetes is a known risk factor for PC, and new-onset diabetes (NOD) could be an early manifestation of PC that may be facilitate the early diagnosis of PC. Metformin offers a clear benefit of inhibiting PC, whereas insulin therapy may increase the risk of PC development. No evidence has shown that novel hypoglycemic drugs help or prevent PC. In this review, the effects of T2DM on PC development are summarized, and novel strategies for the prevention and treatment of T2DM and PC are discussed.
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Affiliation(s)
- Xiaoye Duan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Weihao Wang
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Qi Pan
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Lixin Guo
- Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Roy A, Sahoo J, Kamalanathan S, Naik D, Mohan P, Kalayarasan R. Diabetes and pancreatic cancer: Exploring the two-way traffic. World J Gastroenterol 2021; 27:4939-4962. [PMID: 34497428 PMCID: PMC8384733 DOI: 10.3748/wjg.v27.i30.4939] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 06/16/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is often associated with a poor prognosis. Long-standing diabetes mellitus is considered as an important risk factor for its development. This risk can be modified by the use of certain antidiabetic medications. On the other hand, new-onset diabetes can signal towards an underlying PC in the elderly population. Recently, several attempts have been made to develop an effective clinical tool for PC screening using a combination of history of new-onset diabetes and several other clinical and biochemical markers. On the contrary, diabetes affects the survival after treatment for PC. We describe this intimate and complex two-way relationship of diabetes and PC in this review by exploring the underlying pathogenesis.
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Affiliation(s)
- Ayan Roy
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Pazhanivel Mohan
- Department of Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Raja Kalayarasan
- Department of Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
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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: 187] [Impact Index Per Article: 46.8] [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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10
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Hou J, Li X, Xie KP. Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication. Mol Cancer 2021; 20:34. [PMID: 33593396 PMCID: PMC7888169 DOI: 10.1186/s12943-021-01309-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 01/06/2021] [Indexed: 02/08/2023] Open
Abstract
Early detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks. The potential of liquid biopsies in pancreatic cancer has been demonstrated by many studies which prove that liquid biopsies are able to detect early emergency of pancreatic cancer cells, residual disease, and recurrence. More interestingly, they show potential to delineate the heterogeneity, spatial and temporal, of pancreatic cancer. However, the performance of liquid biopsies for the diagnosis varies largely across different studies depending of the technique employed and also the type and stage of the tumor. One approach to improve the detect performance of liquid biopsies is to intensively inspect circulome and to define integrated biomarkers which simultaneously profile circulating tumor cells and DNA, extracellular vesicles, and circulating DNA, or cell free DNA and proteins. Moreover, the diagnostic validity and accuracy of liquid biopsies still need to be comprehensively demonstrated and validated.
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Affiliation(s)
- Jun Hou
- The South China University of Technology School of Medicine, 510006, Guangzhou, China
| | - XueTao Li
- The South China University of Technology School of Medicine, 510006, Guangzhou, China
| | - Ke-Ping Xie
- The University of Texas MD Anderson Cancer Center Houston , Texas, USA.
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11
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Lee T, Teng TZJ, Shelat VG. Carbohydrate antigen 19-9 - tumor marker: Past, present, and future. World J Gastrointest Surg 2020; 12:468-490. [PMID: 33437400 PMCID: PMC7769746 DOI: 10.4240/wjgs.v12.i12.468] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/06/2020] [Accepted: 12/11/2020] [Indexed: 02/06/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a cell surface glycoprotein complex most commonly associated with pancreatic ductal adenocarcinoma (PDAC). Koprowski first described it in 1979 using a mouse monoclonal antibody in a colorectal carcinoma cell line. Historically, it is one of the most commonly used tumor markers for diagnosing, managing, and prognosticating PDAC. Additionally, elevated CA 19-9 levels are used as an indication for surgery in suspected benign pancreatic conditions. Another common application of CA 19-9 in the biliary tract includes its use as an adjunct in diagnosing cholangiocarcinoma. However, its clinical value is not limited to the hepatopancreatobiliary system. The reality is that the advancing literature has broadened the clinical value of CA 19-9. The potential value of CA 19-9 in patients' workup extends its reach to gastrointestinal cancers - such as colorectal and oesophageal cancer - and further beyond the gastrointestinal tract - including urological, gynecological, pulmonary, and thyroid pathologies. Apart from its role in investigations, CA 19-9 presents a potential therapeutic target in PDAC and acute pancreatitis. In a bid to consolidate its broad utility, we appraised and reviewed the biomarker's current utility and limitations in investigations and management, while discussing the potential applications for CA 19-9 in the works for the future.
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Affiliation(s)
- Tsinrong Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Thomas Zheng Jie Teng
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Vishal G Shelat
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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12
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Zhang J, Zhang Y, Li Y, Guo S, Yang G. Identification of Cancer Biomarkers in Human Body Fluids by Using Enhanced Physicochemical-incorporated Evolutionary Conservation Scheme. Curr Top Med Chem 2020; 20:1888-1897. [PMID: 32648847 DOI: 10.2174/1568026620666200710100743] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 03/01/2020] [Accepted: 03/02/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Cancer is one of the most serious diseases affecting human health. Among all current cancer treatments, early diagnosis and control significantly help increase the chances of cure. Detecting cancer biomarkers in body fluids now is attracting more attention within oncologists. In-silico predictions of body fluid-related proteins, which can be served as cancer biomarkers, open a door for labor-intensive and time-consuming biochemical experiments. METHODS In this work, we propose a novel method for high-throughput identification of cancer biomarkers in human body fluids. We incorporate physicochemical properties into the weighted observed percentages (WOP) and position-specific scoring matrices (PSSM) profiles to enhance their attributes that reflect the evolutionary conservation of the body fluid-related proteins. The least absolute selection and shrinkage operator (LASSO) feature selection strategy is introduced to generate the optimal feature subset. RESULTS The ten-fold cross-validation results on training datasets demonstrate the accuracy of the proposed model. We also test our proposed method on independent testing datasets and apply it to the identification of potential cancer biomarkers in human body fluids. CONCLUSION The testing results promise a good generalization capability of our approach.
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Affiliation(s)
- Jian Zhang
- School of Computer and Information Technology, Xinyang Normal University, Xinyang, China
| | - Yu Zhang
- Information Engineering College, Huanghuai University, Zhumadian, China
| | - Yanlin Li
- School of Computer and Information Technology, Xinyang Normal University, Xinyang, China
| | - Song Guo
- School of Computer and Information Technology, Xinyang Normal University, Xinyang, China
| | - Guifu Yang
- College of Information Science and Technology, Northeast Normal University, Changchun, China
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13
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Kaleru T, Vankeshwaram VK, Maheshwary A, Mohite D, Khan S. Diabetes Mellitus in the Middle-Aged and Elderly Population (>45 Years) and Its Association With Pancreatic Cancer: An Updated Review. Cureus 2020; 12:e8884. [PMID: 32742851 PMCID: PMC7388804 DOI: 10.7759/cureus.8884] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus (DM) and pancreatic cancer (PC) in the elderly are widely considered to be interrelated. New-onset diabetes (NOD) patients are considered a high-risk group for the development of PC within three years of diagnosis. We reviewed the literature to determine the pathophysiological association between DM and PC, which can help in the development of screening tests for early PC diagnosis in the elderly with NOD. We also studied the potential associations between them after pancreaticoduodenectomy (PD) or pancreatic resection. We collected studies published in the last five years in PubMed that are relevant to DM and PC in the elderly. We mainly focused on the pathophysiology and intracellular mechanisms involved between NOD and PC. We illustrated the clinical signs and immunological and metabolic biomarkers that can be used to diagnose early PC in the elderly with NOD. In the 34 studies we reviewed, five showed that long-term diabetes mellitus (LTDM) increases the risk of PC. Six studies showed that NOD in the elderly is an early sign of PC. Fourteen studies proposed that clinical signs and biomarker levels should be used to determine the high-risk risk group for PC among NOD patients. Six studies reported that NOD is associated with the worst outcomes postoperatively, and three studies showed that patients developed DM after pancreatic resection. LTDM is considered an independent risk factor for PC development in the elderly. NOD is a consequence and maybe the only early presenting sign of PC. Screening protocols and tests should be used in clinical practice to determine the proportion of NOD patients who should undergo further testing for early diagnosis of PC. DM and PC are also co-related postoperatively and patients should be monitored for impaired glucose levels, overall survival, and mortality.
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Affiliation(s)
- Thanmai Kaleru
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | | | - Ankush Maheshwary
- Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
- Medicine, Government Medical College, Amritsar, IND
| | - Divya Mohite
- Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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14
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Ikeguchi M, Goto K, Watanabe J, Urushibara S, Osaki T, Endo K, Tatebe S, Nakamura S. Clinical importance of preoperative and postoperative prognostic nutritional index in patients with pancreatic ductal adenocarcinoma. Ann Hepatobiliary Pancreat Surg 2019; 23:372-376. [PMID: 31825004 PMCID: PMC6893056 DOI: 10.14701/ahbps.2019.23.4.372] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 07/11/2019] [Indexed: 12/14/2022] Open
Abstract
Backgrounds/Aims The prognostic nutritional index (PNI) is based on the albumin concentration and absolute lymphocyte count and is designed to assess the nutritional and immunological status of patients. In this study, we evaluated the prognostic importance of the preoperative and postoperative PNI in patients who underwent curative resection of pancreatic ductal adenocarcinoma (PDAC). Methods From 2006 to 2017, 50 patients with PDAC underwent curative resection at our hospital. We performed distal pancreatectomy (DP) with splenectomy in 15 patients, pancreaticoduodenectomy (PD) in 27 patients, PD combined with portal vein partial resection in 6 patients, and total pancreatectomy with splenectomy in 2 patients. We compared the preoperative PNI and postoperative PNI (1 and 2 months postoperatively) and analyzed the prognostic importance for these patients. Results The mean PNI significantly decreased from 45.5 preoperatively to 39.8 at 1 month postoperatively (p<0.001), but recovered to 42.7 at 2 months postoperatively. In 23 patients, the PNI at 2 months postoperatively recovered to the preoperative level (recovered group), but in the remaining 27 patients, the PNI at 2 months postoperatively did not reach the preoperative level (non-recovered group). The overall median survival time in the recovered group (29 months) was significantly longer than that in the non-recovered group (12 months, p=0.003). The multivariate overall analysis demonstrated that good recovery of the postoperative PNI was strongly correlated with a better prognosis. Conclusions Effective postoperative nutrition may have a prognostic benefit for patients with operable PDAC.
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Affiliation(s)
- Masahide Ikeguchi
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Keisuke Goto
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - June Watanabe
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Shoichi Urushibara
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Tomohiro Osaki
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Kanenori Endo
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Shigeru Tatebe
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Seiichi Nakamura
- Department of Surgery, Tottori Prefectural Central Hospital, Tottori, Japan
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15
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Cui L, Lv N, Li B, Tao J, Zheng X, Yan Y, Liu C. Serum CA 19-9 Level is Correlated to the Clinical Characteristics and Chronic Complications of Patients Newly Diagnosed with Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes 2019; 129:581-586. [PMID: 31461764 DOI: 10.1055/a-0994-9970] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIM This study investigated the relation of serum carbohydrate antigen 199 (CA 19-9) levels to the clinical characteristics and chronic complications of patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS A total of 371 patients newly diagnosed with T2DM and 133 healthy people with consecutively matched age were compared. The 371 patients with T2DM were divided into four groups by quartiles based on their serum CA 19-9 levels, in which clinical characteristics and chronic complications, such as diabetic retinopathy (DR), diabetic nephropathy, and macrovascular complications were compared. Logistic regression analysis was used to evaluate the risk factors of DR. RESULTS Among the 371 patients newly diagnosed with T2DM, 60 had elevated CA 19-9 levels (16.17%). The frequencies of elevated serum CA 19-9 were 24.39% (30 of 123) for females and 12.10% (30 of 248) for males, in which the values for females were higher than those for males (P<0.01).Differences were observed among the serum CA 19-9 levels, hemoglobin A1c (HbA1c), and DR (P<0.05). Logistic regression analysis showed that serum CA 19-9 levels, fasting blood glucose (FBG) and fasting C-peptide (FC-P) were risk factors for DR (P<0.05). CONCLUSIONS Serum CA 19-9 levels were correlated with HbA1c and DR in patients newly diagnosed with T2DM. The elevated serum CA 19-9 levels, high FC-P, and FBG levels were important risk factors for DR in patients newly diagnosed with T2DM.
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Affiliation(s)
- Limei Cui
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
| | - Naqiang Lv
- Department of Special Care Center, National Clinical Research Center for Cardiovascular Diseases, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Bin Li
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
| | - Jing Tao
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
| | - Xiaomin Zheng
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
| | - Yehua Yan
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
| | - Cuiping Liu
- Department of Endocrinology, ChuiYangLiu Hospital, Beijing P. R. China
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Lee SP, Sung IK, Kim JH, Lee SY, Park HS, Shim CS. Usefulness of Carbohydrate Antigen 19-9 Test in Healthy People and Necessity of Medical Follow-up in Individuals with Elevated Carbohydrate Antigen 19-9 Level. Korean J Fam Med 2019; 40:314-322. [PMID: 30959581 PMCID: PMC6768838 DOI: 10.4082/kjfm.18.0057] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 07/19/2018] [Indexed: 12/13/2022] Open
Abstract
Background Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker whose level is elevated in many types of cancers and other benign conditions. CA 19-9 levels are frequently found to be elevated in individuals during general health examinations. This study aimed to investigate the clinical characteristics of such individuals and to determine the need for medical follow-up. Methods We investigated individuals who underwent a health inspection, including a serum CA 19-9 test, at our center. Their CA 19-9 levels, age, sex, body mass index (BMI), and personal and past histories were investigated. Additionally, subgroup analyses were performed for those who underwent follow-up study for the elevated CA 19-9 levels. Results Of 58,498 subjects, 581 (1.0%) had elevated CA 19-9 levels. Multivariate analyses revealed that older age, female sex, lower BMI, and diabetes were independent predisposing factors for elevated CA 19-9 level. A subgroup analysis revealed that the causative conditions were identified in 129 of 351 subjects (36.8%). Among them, the causative conditions in 31 subjects (8.8%, including four cases of cancer and 15 of benign tumors) were not detected at the initial check-up and were found during the follow-up period. Conclusion The use of CA 19-9 as a marker for cancer in healthy individuals is inappropriate. However, medical follow-up in individuals with elevated CA 19-9 levels may be useful because some causative diseases may be detected during follow-up.
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Affiliation(s)
- Sang Pyo Lee
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - In-Kyung Sung
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jeong Hwan Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sun-Young Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hyung Seok Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Chan Sup Shim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Abstract
PURPOSE OF REVIEW The relationship between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus (DM) is complex. We reviewed the recent medical literature regarding the effect of anti-diabetic medication on PDAC risk and survival, risk of PDAC in DM, and role of DM in early detection of PDAC. RECENT FINDINGS Studies report that while some anti-diabetic medications (e.g., metformin) may decrease the risk of PDAC, others (insulin, sulfonylureas and incretin-based therapies) may increase the risk. However, these observations may be subject to protopathic biases. Metformin's anti-tumor activity may have influence overall survival of PDAC, but epidemiological reports have largely been inconsistent to defend these findings due to heterogeneous methodologies. There is congruent data to support the association between DM and PDAC, with an inverse relationship to DM duration. Older subjects with new-onset DM are the only known high-risk group for PDAC, and strategy using this group for early detection has led to development of clinical risk prediction models that define a very high-risk PDAC group. Role of anti-diabetic medication in PDAC risk modification or survival is controversial. With successful efforts to distinguish type 2-DM from PDAC-DM using risk-stratifying models, there is an opportunity to initiate screening protocols for early detection of PDAC in a sub-set of DM subjects.
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Affiliation(s)
- Ayush Sharma
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA
| | - Suresh T Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA.
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