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Vitale F, Zileri Dal Verme L, Paratore M, Negri M, Nista EC, Ainora ME, Esposto G, Mignini I, Borriello R, Galasso L, Alfieri S, Gasbarrini A, Zocco MA, Nicoletti A. The Past, Present, and Future of Biomarkers for the Early Diagnosis of Pancreatic Cancer. Biomedicines 2024; 12:2840. [PMID: 39767746 PMCID: PMC11673965 DOI: 10.3390/biomedicines12122840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/30/2024] [Accepted: 12/11/2024] [Indexed: 01/04/2025] Open
Abstract
Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine.
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Affiliation(s)
- Federica Vitale
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Lorenzo Zileri Dal Verme
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Mattia Paratore
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Marcantonio Negri
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Enrico Celestino Nista
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Elena Ainora
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Giorgio Esposto
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Irene Mignini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Raffaele Borriello
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Linda Galasso
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Sergio Alfieri
- Centro Pancreas, Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Assunta Zocco
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Alberto Nicoletti
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
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Thomas DS, Sebastian A, Thomas V, Thomas A, Chandy RG, Peedicayil A. Diagnostic Accuracy of CA 19-9 in Ovarian Malignancy. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2024; 22:73. [DOI: 10.1007/s40944-024-00829-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 02/24/2024] [Accepted: 04/07/2024] [Indexed: 01/03/2025]
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Pendry SD, Singhal N, Neo E, Foreman D, Winter JM. Elevation of the tumor marker CA19-9 in a pancreatic cancer survivor with benign prostatic hyperplasia: A clinical case report. Clin Case Rep 2024; 12:e8929. [PMID: 38799519 PMCID: PMC11126644 DOI: 10.1002/ccr3.8929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/24/2024] [Accepted: 05/03/2024] [Indexed: 05/29/2024] Open
Abstract
Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.
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Affiliation(s)
- Steve D. Pendry
- Flinders Health and Medical ResearchCollege of Medicine and Public Health Flinders UniversityBedford ParkSouth AustraliaAustralia
| | - Nimit Singhal
- Cancer Centre, Royal Adelaide Hospital and School of MedicineThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Eu‐Ling Neo
- Hepatopancreatobiliary Surgical UnitFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- Hepatobiliary Surgical UnitRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Darren Foreman
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Jean M. Winter
- Flinders Health and Medical ResearchCollege of Medicine and Public Health Flinders UniversityBedford ParkSouth AustraliaAustralia
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Ciesielka J, Jakimów K, Tekiela N, Peisert L, Kwaśniewska A, Kata D, Chudek J. Significantly Elevated CA 19-9 after COVID-19 Vaccination and Literature Review of Non-Cancerous Cases with CA 19-9 > 1000 U/mL. J Clin Med 2024; 13:1263. [PMID: 38592088 PMCID: PMC10932348 DOI: 10.3390/jcm13051263] [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: 01/22/2024] [Revised: 02/15/2024] [Accepted: 02/19/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND CA 19-9 is a commonly assessed tumor marker, considered characteristic of pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers; however, the positive predictive value of CA 19.9 is too low, and the usage of CA 19.9 as a screening tool in the healthy population remains controversial. METHODS The presented case illustrates a reversed diagnosis of highly elevated serum CA 19-9 levels in a 54-year-old female complaining of pain in the epigastric region, shortly after COVID-19 vaccination. Laboratory tests showed a significantly elevated level of the CA 19-9 marker (>12,000 U/mL, reference value: <37 U/mL) with normal pancreatic enzyme activity. The patient underwent imaging examination, which showed no abnormalities, except for increased pancreatic dimension and areas of fluid signal in the pancreas in magnetic resonance imaging (MRI), which may correspond to autoimmune pancreatitis (AIP). The patient remains asymptomatic with a recommendation for a follow-up MRI in 12 months. RESULTS A literature review conducted revealed multi-causal CA 19-9 increases above 1000 U/mL, including non-cancerous diseases of the lung, pancreas, liver, ovary, kidney, and others. The median concentration of CA 19-9 regardless of the cause of disease was 2810 U/mL (IQR ± 6895). The median CA 19-9 values in men and women were 3500 (IQR ± 10,050) and 2455 (IQR ± 3927), respectively, and differ significantly between the compared groups (p < 0.05). There was no difference between CA 19-9 values and the categorized cause of the increase. CONCLUSIONS Conducting differential diagnosis, it should not be forgotten that most international guidelines recommend the use of CA 19-9 only in conjunction with pathology of pancreas in radiological imaging; however, even such a combination can point the diagnostic pathway in the wrong direction. A highly elevated CA 19-9 level, typically associated with PDAC, may be the result of benign disease including AIP related to COVID-19 vaccination.
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Affiliation(s)
- Jakub Ciesielka
- Student’s Research Group, Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-055 Katowice, Poland; (K.J.); (N.T.); (L.P.)
| | - Krzysztof Jakimów
- Student’s Research Group, Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-055 Katowice, Poland; (K.J.); (N.T.); (L.P.)
| | - Natalia Tekiela
- Student’s Research Group, Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-055 Katowice, Poland; (K.J.); (N.T.); (L.P.)
| | - Laura Peisert
- Student’s Research Group, Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-055 Katowice, Poland; (K.J.); (N.T.); (L.P.)
| | - Anna Kwaśniewska
- Department of Radiology, The Mielecki Hospital, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
| | - Dariusz Kata
- Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Jerzy Chudek
- Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-055 Katowice, Poland
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Trapé J, Fernández-Galán E, Auge JM, Carbonell-Prat M, Filella X, Miró-Cañís S, González-Fernández C. Factors influencing blood tumor marker concentrations in the absence of neoplasia. Tumour Biol 2024; 46:S35-S63. [PMID: 38517826 DOI: 10.3233/tub-220023] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2024] Open
Abstract
BACKGROUND Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results. MATERIAL AND METHODS AND RESULTS Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), β2-microglobulin (β2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included. CONCLUSIONS A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.
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Affiliation(s)
- Jaume Trapé
- Department of Laboratory Medicine, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Catalonia, Spain
- Tissue Repair and Regeneration Laboratory, Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central, Barcelona, Spain
- Faculty of Medicine, University of Vic - Central University of Catalonia, Vic, Spain
| | - Esther Fernández-Galán
- Department of Biochemistry and Molecular Genetics - Hospital Clinic de Barcelona, Barcelona, Spain
| | - Josep Maria Auge
- Department of Biochemistry and Molecular Genetics - Hospital Clinic de Barcelona, Barcelona, Spain
| | | | - Xavier Filella
- Department of Biochemistry and Molecular Genetics - Hospital Clinic de Barcelona, Barcelona, Spain
| | - Sílvia Miró-Cañís
- Laboratori d'Anàlisis Clíniques, CLILAB Diagnòstics, Vilafranca del Penedès, Spain
| | - Carolina González-Fernández
- Department of Laboratory Medicine, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Catalonia, Spain
- Gastrointestinal Oncology, Endoscopy and Surgery Research Group, Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central, Barcelona, Spain
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Nichols L, Lawrence R, Haboubi H, Al-Sarireh B, Doak S, Jenkins G. Measuring blood cell DNA damage using the PIG-A mutation and CBMN assay in pancreatic cancer patients: a pilot study. Mutagenesis 2023; 38:93-99. [PMID: 37006185 PMCID: PMC10181792 DOI: 10.1093/mutage/gead006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 03/29/2023] [Indexed: 04/04/2023] Open
Abstract
Pancreatic cancer still has one of the worst prognoses of all solid malignancies, despite developments in cancer knowledge and care. Research into pancreatic cancer has not fully translated into clinical improvements and as a result, fewer than 1% of patients survive 10 years post-diagnosis. This bleak outlook for patients could be improved by earlier diagnosis. The human erythrocyte phosphatidylinositol glycan class A (PIG-A) assay monitors the mutation status of the X-linked PIG-A gene by measuring glycosyl phosphatidylinositol (GPI)-anchored proteins on the extracellular surface. We have previously identified an elevated PIG-A mutant frequency in oesophageal adenocarcinoma patients and here investigate whether this could be seen in a pancreatic cancer cohort, given the urgent need for novel pancreatic cancer biomarkers. In our pilot study, an elevated PIG-A mutant frequency (5.775 × 10-6 (95% CI 4.777-10) mutants per million) was seen in pancreatic cancer patients (n = 30) when compared to the non-cancer control group (n = 14) who had an erythrocyte mutant frequency of 4.211 × 10-6 (95% CI 1.39-5.16) mutants per million (p = 0.0052). A cut-off value of 4.7 mutants per million provided an AUROC of 0.7595 with a sensitivity of 70% and specificity of 78.57%. A secondary measure of DNA damage in an alternative blood cell population also showed an increase in peripheral lymphocytes using the cytokinesis-block micronucleus assay (p = 0.0164) (AUROC = 0.77, sensitivity = 72.22%, specificity = 72.73%). The micronucleus frequency and PIG-A status show some potential as blood-based biomarkers of pancreatic cancer, but further investigations of these DNA damage tests are required to assess their utility in pancreatic cancer diagnosis.
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Affiliation(s)
- Lucy Nichols
- Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom
| | - Rachel Lawrence
- Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom
| | - Hasan Haboubi
- Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom
| | - Bilal Al-Sarireh
- Department of Pancreato-biliary surgery, Morriston Hospital, Swansea, United Kingdom
| | - Shareen Doak
- Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom
| | - Gareth Jenkins
- Swansea University Medical School, Swansea University, Singleton Park, Swansea, United Kingdom
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Yang CY, Lin RT, Chen CY, Yeh CC, Tseng CM, Huang WH, Lee TY, Chu CS, Lin JT. Accuracy of simultaneous measurement of serum biomarkers: Carbohydrate antigen 19-9, pancreatic elastase-1, amylase, and lipase for diagnosing pancreatic ductal adenocarcinoma. J Formos Med Assoc 2022; 121:2601-2607. [DOI: 10.1016/j.jfma.2022.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 05/05/2022] [Accepted: 07/11/2022] [Indexed: 12/22/2022]
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Elevated carbohydrate antigen 19-9 following Helicobacter suis gastritis and normalisation after eradication: first case report and review of the literature. Acta Gastroenterol Belg 2022; 85:403-405. [DOI: 10.51821/85.2.8826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a biological marker used to diagnose and monitor the progression of various cancers. Elevated CA 19-9 has also been sporadically observed in Helicobacter pylori infected patients. Similar to H. pylori, animal- hosted non-H. pylori Helicobacter (NHPH) species can induce gastroduodenal lesions in humans. We report the first case of CA 19-9 elevation related to H. suis gastritis and its normalisation after eradication. A CA 19-9 screening prescribed as part of a regular check up by the general practitioner was found elevated in a 68-year-old man presenting chronic dyspeptic symptoms. Medical investigations were negative for presence of neoplasia or biliary obstruction. Upper gastrointestinal endoscopy confirmed the presence of chronic gastritis and H. suis was identified in gastric biopsies. The standard treatment for H. pylori successfully eradicated H. suis with normalisation of CA 19-9 levels. In addition to H. pylori, infection with NHPH species should be considered as an additional cause of elevated CA19-9.
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Retroperitoneal Bronchogenic Cyst Mimicking a Pancreatic Cystic Lesion with Extremely High Level of Intralesional Fluid CA-19.9 Antigen: Benign in Disguise. Indian J Surg 2021; 84:556-561. [PMID: 34848933 PMCID: PMC8613729 DOI: 10.1007/s12262-021-03137-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 09/25/2021] [Indexed: 10/26/2022] Open
Abstract
Bronchogenic cysts are congenital benign tumors resulting from abnormal budding of the primitive foregut. Usually presented on the posterior mediastinum, its presence on the retroperitoneum is extremely rare. We present an asymptomatic lady patient with a retroperitoneal cystic lesion that was submitted to endoscopic ultrasound-guided biopsies and intracystic fluid aspiration with histology excluding malignance despite intracystic fluid biochemical analysis that disclosed extremely high carbohydrate antigen 19-9. Definite diagnosis of bronchogenic cyst was only possible after complete surgical resection of the lesion. Furthermore, we discuss the use of this antigen as a tumor marker in this situation and its relevance to the preoperative diagnosis of such lesions.
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Strainiene S, Sedleckaite K, Jarasunas J, Savlan I, Stanaitis J, Stundiene I, Strainys T, Liakina V, Valantinas J. Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review. World J Clin Cases 2021; 9:6155-6169. [PMID: 34368338 PMCID: PMC8316968 DOI: 10.12998/wjcc.v9.i21.6155] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/30/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience.
CASE SUMMARY A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo.
CONCLUSION IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.
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Affiliation(s)
- Sandra Strainiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | | | - Juozas Jarasunas
- Department of Radiology, Nuclear Medicine and Medical Physics, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ilona Savlan
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Juozas Stanaitis
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Ieva Stundiene
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Tomas Strainys
- Clinic of Anesthesiology and Intensive Care Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
| | - Valentina Liakina
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
- Department of Chemistry and Bioengineering, Faculty of Fundamental Science, Vilnius Gediminas Technical University, Vilnius 10223, Lithuania
| | - Jonas Valantinas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 01513, Lithuania
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Rasappan K, Shaw LKRMY, Chan LWM, Chuah KL, Cheng MHW. A case of raised CA 19-9 in a patient with desmoplastic fibroblastoma of the upper limb. Int Cancer Conf J 2021; 10:222-227. [PMID: 34221836 PMCID: PMC8206393 DOI: 10.1007/s13691-021-00485-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 04/16/2021] [Indexed: 02/06/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker widely accepted as the most useful blood test in diagnosing and monitoring pancreatic cancer. However, CA 19-9 may also be raised in other conditions such as colorectal, hepatic, lung, and ovarian carcinoma as well as benign conditions such as hepatobiliary and pulmonary diseases. CA 19-9 is rarely elevated above 200 U/ml in benign conditions with values exceeding 1000 U/ml being highly suggestive of malignancy. The mechanism of secretion in both malignant and benign conditions remains unclear. Desmoplastic fibroblastoma (DF) is a benign soft tissue tumor. CA 19-9 has not been reported in association with DF previously. We present a case of raised serum CA 19-9 in a 71-year-old male attributed solely to DF in his left cubital fossa. The patient's CA 19-9 level rose from 56 U/ml at the time of presentation to 3763.8 U/ml over a period of 9 months. Post-DF excision, the CA 19-9 level decreased to 1464 U/ml at 1 month, 162.3 U/ml at 2.5 months, and 24U/ml, within normal range, at 7 months post-surgery. CA 19-9 levels continued to remain at 24 U/ml 1.5 years post-tumor excision. The CA 19-9 level in this patient was highly elevated which is unusual in association with a benign tumor. The rate of decrease in CA 19-9 level post-excision was in keeping with that reported after pancreatic cancer resections. This is the first case of DF in association with raised CA 19-9.
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Affiliation(s)
- Kumaran Rasappan
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
| | | | - Lester Wai Mon Chan
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
| | - Khoon Leong Chuah
- grid.240988.fDepartment of Pathology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Mathew Hern Wang Cheng
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
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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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Association of serum carbohydrate antigen 19-9 level with arterial stiffness and coronary artery calcification in middle-aged and older adults. J Hypertens 2020; 38:95-101. [DOI: 10.1097/hjh.0000000000002217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Pils S, Paternostro C, Mayerhoefer ME, Reinthaller A, Feichtinger M. Heavy black tea consumption and elevated CA 19-9 and CA 125 levels. A case report on a patient with ovarian endometriotic cysts. Gynecol Endocrinol 2019; 35:478-480. [PMID: 30727790 DOI: 10.1080/09513590.2018.1564743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In this case report, we present a case of false positive CA 19-9 and CA 125 levels in a patient with suspected endometriotic cysts. The patient is a 34-year-old nulliparous woman with heavy black tea consumption and elevated CA 19-9 and CA 125 levels. After discontinuation of black tea intake and careful exploration of other possible factors, CA 19-9 and CA 125 levels dropped markedly. As a conclusion, heavy black tea consumption can lead to false positive results of elevated CA 19-9 and CA 125 levels.
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Affiliation(s)
- Sophie Pils
- a Department of Gynecology and Gynecological Oncology , Gynecologic Cancer Unit Comprehensive Cancer Center Medical University of Vienna , Vienna , Austria
| | - Chiara Paternostro
- a Department of Gynecology and Gynecological Oncology , Gynecologic Cancer Unit Comprehensive Cancer Center Medical University of Vienna , Vienna , Austria
| | - Marius E Mayerhoefer
- b Department of Biomedical Imaging and Image-Guided Therapy , Medical University of Vienna , Vienna , Austria
| | - Alexander Reinthaller
- a Department of Gynecology and Gynecological Oncology , Gynecologic Cancer Unit Comprehensive Cancer Center Medical University of Vienna , Vienna , Austria
| | - Michael Feichtinger
- a Department of Gynecology and Gynecological Oncology , Gynecologic Cancer Unit Comprehensive Cancer Center Medical University of Vienna , Vienna , Austria
- c Wunschbaby Institut Feichtinger , Vienna , Austria
- d Department of Oncology-Pathology , Karolinska Institutet , Stockholm , Sweden
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Tsen A, Barbara M, Rosenkranz L. Dilemma of elevated CA 19-9 in biliary pathology. Pancreatology 2018; 18:862-867. [PMID: 30249386 DOI: 10.1016/j.pan.2018.09.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 09/13/2018] [Accepted: 09/18/2018] [Indexed: 12/11/2022]
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker which has been extensively evaluated and widely utilized primarily in diagnosing and prognosticating pancreaticobiliary malignancies. Levels may be significantly influenced and elevated in cases of benign biliary conditions however, especially in obstructive jaundice, thereby posing difficulty in distinguishing between benign and malignant cholestasis. A myriad of studies have focused on elucidating proper use and interpretation of CA 19-9 in pancreatic cancer as well as in the setting of cholestasis. These studies have demonstrated that many factors influence CA 19-9 values and various methods for interpreting CA 19-9 in obstructive jaundice have been proposed. With improvements in diagnostic imaging, advancements in endoscopic modalities, and likelihood that management will not change based on the results of the test, clinicians should be cautious when ordering CA 19-9 and consider the reasons for measuring the tumor marker.
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Affiliation(s)
- Adrianne Tsen
- University of Texas Health Science Center at San Antonio, 5623 Hamilton Wolfe, #712, San Antonio, TX 78240, USA.
| | - Mary Barbara
- Department of Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Laura Rosenkranz
- Department of Gastroenterology and Advanced Therapeutic Endoscopy, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Kotzev AI, Draganov PV. Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, and Carbohydrate Antigen 72-4 in Gastric Cancer: Is the Old Band Still Playing? Gastrointest Tumors 2018; 5:1-13. [PMID: 30574476 DOI: 10.1159/000488240] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 03/08/2018] [Indexed: 12/12/2022] Open
Abstract
Background Gastric cancer (GC) is characterized by aggressive behavior and a high mortality rate. The diagnosis of GC is challenging because the GC is often diagnosed in an advanced stage. The use of tumor markers is a putative way to improve the detection and treatment in patients with GC. Summary In this article, we review the significance of serum carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA 72-4 in GC. The results from different studies regarding the diagnostic and prognostic role of CA 19-9, CEA, and CA 72-4 in GC are encouraging, but inadequate sensitivity and specificity obstruct their use as standardized and unconditionally reliable markers in GC. New prospective clinical trials are mandatory for clarifying their value in GC. Key Message CA 19-9, CEA, and CA 72-4 should not be used for screening and early diagnosis in GC, whereas they are beneficial in the detection of late GC. CA 19-9, CEA, and CA 72-4 could be used as prognostic and monitoring tools in GC, and their combined measurement in shorter periods of time is the best method to increase sensitivity and specificity. Practical Implications Serum CA 19-9, CEA, and CA 72-4 are useful diagnostic and prognostic tumor markers in GC.
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Affiliation(s)
- Andrey Iskrenov Kotzev
- Clinic of Gastroenterology, University Hospital "Alexandrovska," Medical University Sofia, Sofia, Bulgaria
| | - Peter Vassilev Draganov
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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Laengsri V, Kerdpin U, Plabplueng C, Treeratanapiboon L, Nuchnoi P. Cervical Cancer Markers: Epigenetics and microRNAs. Lab Med 2018; 49:97-111. [DOI: 10.1093/labmed/lmx080] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Vishuda Laengsri
- Center for Research & Innovation, Mahidol University, Bangkok, Thailand
- Department of Clinical Microscopy, Mahidol University, Bangkok, Thailand
| | - Usanee Kerdpin
- Department of Chemistry, Faculty of Science, Naresuan University, Phitsanulok, Thailand
| | - Chotiros Plabplueng
- Center for Research & Innovation, Mahidol University, Bangkok, Thailand
- Department of Clinical Microscopy, Mahidol University, Bangkok, Thailand
| | - Lertyot Treeratanapiboon
- Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
| | - Pornlada Nuchnoi
- Center for Research & Innovation, Mahidol University, Bangkok, Thailand
- Department of Clinical Microscopy, Mahidol University, Bangkok, Thailand
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18
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Chen J, Liu Q, Ling Y, Yang H, Wen J, Luo K, Hu Y, Tan Z, Fu J. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report. Clin Chem Lab Med 2017; 55:e279-e281. [PMID: 28672729 DOI: 10.1515/cclm-2017-0001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 04/21/2017] [Indexed: 12/12/2022]
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AL-Janabi AAHS, Tawfeeq EF. Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9. J Gastrointest Cancer 2016; 48:148-150. [DOI: 10.1007/s12029-016-9855-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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20
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Wu E, Zhou S, Bhat K, Ma Q. CA 19-9 and pancreatic cancer. CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY : H&O 2013; 11:53-55. [PMID: 23596673 PMCID: PMC3633106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Affiliation(s)
- Erxi Wu
- Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA.
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21
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Abstract
Autoimmune cholangitis, immunoglobulin G4-associated cholangitis (IAC), is a part of multiorgan IgG4-related systemic disease, which was recognized as a new clinicopathological entity in recent years. IAC is defined as a biliary stricture that responds to steroid therapy, frequently is associated with other fibrosing conditions, especially autoimmune pancreatitis and is characterized by elevation of IgG4 in serum and infiltration of IgG4 positive plasma cells in bile ducts. Since IAC shares a number of clinical, biochemical, and imaging features with cholangiocarcinoma (CCA), it is often misdiagnosed as CCA, and unnecessary surgery was performed. In this compact review, we clarify the disease of IAC, summarize criteria for diagnosis of IAC, discuss the role of CA 19-9, and provide key information to differentiate diagnosis of IAC from CCA. IAC should be highly suspected in unexplained biliary stricture associated with increased IgG4 (in serum especially in bile) and other organ involvement (kidney, retroperitoneum etc. especially pancreas in which there are abundant IgG4-positive plasmocytes infiltration). Correct diagnosis of IAC will avoid unnecessary surgery because IAC responds well to steroid therapy. In a word, increased IgG4 levels, other organ involvement and response to steroids are keys to distinguishing IAC from CCA.
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Affiliation(s)
- Jun Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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22
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La Greca G, Sofia M, Lombardo R, Latteri S, Ricotta A, Puleo S, Russello D. Adjusting CA19-9 values to predict malignancy in obstructive jaundice: Influence of bilirubin and C-reactive protein. World J Gastroenterol 2012; 18:4150-5. [PMID: 22919247 PMCID: PMC3422795 DOI: 10.3748/wjg.v18.i31.4150] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Revised: 04/27/2012] [Accepted: 05/05/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ).
METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment.
RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively.
CONCLUSION: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.
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23
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Cure MC, Cure E, Kirbas A, Yazici T, Yuce S. Requests for tumor marker tests in Turkey without indications and frequency of elevation in benign conditions. Asian Pac J Cancer Prev 2012; 13:6485-9. [PMID: 23464479 DOI: 10.7314/apjcp.2012.13.12.6485] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
AIMS To investigate the incidence of ordering tests for tumor markers which are used in cancer diagnosis, follow-up treatment and detection of recurrence, the rate of elevation in benign diseases and which clinics order them frequently. MATERIALS AND METHOD Data for the tumor markers carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3) and alpha- fetoprotein (AFP) that were ordered by all the clinics in our Hospital between 2010 and 2011 were screened. When excluding repeated orders the results of 3,416 patients were available. It has been determined that in which benign diseases were the tumor markers frequently ordered and which of these conditions had high levels of them. RESULTS CA 19-9 was ordered for 1,858 patients 191 (10.3%) were malignant while 1667 (89.7%) were ordered in benign diseases. For CEA the total was 1,710, 226 (13.2%) malignant and 1484 (86.8%) benign, and for CA 125 1267, 111 (8.8%) malignant and 1156 (91.2%) benign. AFP was ordered for 1687 cases, 80 (4.7%) malignant but 1607 (95.3%) benign. CA 15-3 was ordered 1449 times, 174 (12%) for malignant and 1275 (88%) for benign diseases. In all cases, considerable proportions were positive. CONCLUSIONS It was shown that clinicians frequently order tumor markers for benign conditions. The findings of this study has shown that tumor markers are used widely without indications as cancer screening tests.
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Affiliation(s)
- Medine Cumhur Cure
- Department of Biochemisty, University of Recep Tayyip Erdogan, Rize, Turkey.
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Molina V, Visa L, Conill C, Navarro S, Escudero JM, Auge JM, Filella X, Lopez-Boado MA, Ferrer J, Fernandez-Cruz L, Molina R. CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer. Tumour Biol 2011; 33:799-807. [PMID: 22203495 DOI: 10.1007/s13277-011-0297-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2011] [Accepted: 12/06/2011] [Indexed: 12/13/2022] Open
Abstract
CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability.
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Affiliation(s)
- Victor Molina
- Department of General and Digestive Surgery, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain
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Trapé J, Filella X, Alsina-Donadeu M, Juan-Pereira L, Bosch-Ferrer Á, Rigo-Bonnin R. Increased plasma concentrations of tumour markers in the absence of neoplasia. Clin Chem Lab Med 2011; 49:1605-20. [PMID: 21892908 DOI: 10.1515/cclm.2011.694] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Tumour markers are a very heterogeneous group of molecules that are generally found in very small concentrations in the plasma and serum of healthy individuals. In the process of neoplastic differentiation the cell can synthesize, release, or induce synthesis of other cells, thus increasing their concentration in plasma and serum. These substances may also increase their plasma concentration in patients without cancer due to processes that increase the release or reduce catabolism, and so give rise to false positives. An understanding of the main physiopathological processes that increase the concentrations of these substances could improve our interpretation of tumour markers and their clinical application. In this study we review the physiopathological processes that may increase the plasma concentrations of tumour markers. We performed a bibliography review in PubMed, searching for causes of false positives for the following tumour markers: α-Fetoprotein, CA 125, CA 15-3, CA 19-9, CA 72-4, carcinoembryonic antigen, CYFRA 21-1, squamous cell carcinoma, prostatic specific antigen, β(2)-microglobulin, choriogonadotropin (β chain), chromogranin A, neuron specific enolase, HER2-neu, progastrin releasing peptide, S-100, and thyroglobulin. The results favour the use of tests which can identify pathological processes that may increase tumour marker concentrations.
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Affiliation(s)
- Jaume Trapé
- Laboratory Medicine, Biological Diagnosis Department, Manresa Althaia Xarxa Assistencial de Manresa, Manresa, Catalonia, Spain.
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26
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Waanders E, van Keimpema L, Brouwer JT, van Oijen MGH, Aerts R, Sweep FCGJ, Nevens F, Drenth JPH. Carbohydrate antigen 19-9 is extremely elevated in polycystic liver disease. Liver Int 2009; 29:1389-95. [PMID: 19515221 DOI: 10.1111/j.1478-3231.2009.02055.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Carbohydrate antigen 19-9 (CA19-9) is used as a biomarker to differentiate benign from malignant gastrointestinal disorders. We examined the value of CA19-9 measurement in polycystic livers after observing high CA19-9 cyst fluid levels in a benign polycystic liver case. METHODS We determined CA19-9 levels in serum (n=120) and hepatic cyst fluid (n=81), from patients with polycystic livers (n=109) and simple hepatic cysts (n=24). Further, we analysed CA19-9 expression in normal and polycystic liver tissue (n=17). RESULTS Cyst fluid CA19-9 levels from both polycystic livers and simple hepatic cysts were extremely high (median 91 000 U/ml, range 14-15 870 000 U/ml; median 85 000 U/ml, range 332-1 744 000 U/ml respectively). Serum CA19-9 levels were significantly higher in polycystic liver patients (median 30 U/ml, range 0-1200 U/ml) compared with patients with simple hepatic cysts (median 10 U/ml, range 3-200 U/ml, P=0.0011). Serum CA19-9 levels correlated with those in cyst fluid (r=0.3979, P=0.0399), polycystic liver volume (r=0.3870, P=0.0025) and the size of the largest cyst (simple cysts group; r=0.5319, P=0.0280). Cyst epithelia showed strong CA19-9 expression. Evacuation of cyst fluid in four patients resulted in a dramatic decrease in the serum CA19-9 levels (60-95%). CONCLUSIONS CA19-9 levels are high in the cyst fluid and serum of polycystic liver disease patients due to production and secretion by cyst epithelia. It does not reflect malignancy in these patients and may be of value as a biomarker for intervention efficiency assessment.
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Affiliation(s)
- Esmé Waanders
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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Ventrucci M, Pozzato P, Cipolla A, Uomo G. Persistent elevation of serum CA 19-9 with no evidence of malignant disease. Dig Liver Dis 2009; 41:357-63. [PMID: 18602352 DOI: 10.1016/j.dld.2008.04.002] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2007] [Revised: 04/03/2008] [Accepted: 04/07/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Serum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases. AIMS In this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed. PATIENTS Nine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one. METHODS Routine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission. RESULTS Serum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2-7 years) serum CA 19-9 values were persistently elevated in all patients. CONCLUSIONS Our study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.
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Affiliation(s)
- M Ventrucci
- Department of Internal Medicine and Gastroenterology, Bentivoglio Hospital, Bologna, Italy.
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Kim BJ, Lee KT, Moon TG, Kang P, Lee JK, Kim JJ, Rhee JC. How do we interpret an elevated carbohydrate antigen 19-9 level in asymptomatic subjects? Dig Liver Dis 2009; 41:364-9. [PMID: 19162573 DOI: 10.1016/j.dld.2008.12.094] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2008] [Revised: 11/25/2008] [Accepted: 12/03/2008] [Indexed: 12/11/2022]
Abstract
AIM This prospective cohort study aimed to evaluate the etiology of elevated CA 19-9 levels and to present appropriate guidelines for the asymptomatic patients. METHODS Between January 2004 and March 2007, we enrolled consecutive asymptomatic patients who had elevated CA 19-9 levels >37 U/mL. To evaluate the etiology, the CA 19-9 level was rechecked and further studies were carried out. If the CA 19-9 level decreased to the normal range, or if it showed a decreasing trend, then it was monitored annually. Yet, if the CA 19-9 level showed an increasing trend, then the level was monitored at intervals of 1, 3, and 6 months until no evidence of malignancy was proven. RESULTS Of the 62,976 patients, 501 (0.8%) subjects showed an elevated CA 19-9 level. This prospective analysis was conducted on 353 subjects (70.5%) who were followed up for at least 6 months. Ten patients (2.8%) were diagnosed with malignancies. There were 97 patients (27.5%) with benign diseases and 246 patients (69.7%) were deemed non-specific. CONCLUSIONS CA 19-9 should not be used as a screening tool. In the case of a persistently elevated CA 19-9 level, further work-up for determining the etiology should be done.
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Affiliation(s)
- B J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
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