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Bruni A, Eusebi LH, Lisotti A, Ricci C, Maida M, Fusaroli P, Barbara G, Sadik R, Pagano N, Hedenström P, Marasco G. Intracystic Glucose Measurement for On-Site Differentiation Between Mucinous and Non-Mucinous Pancreatic Cystic Lesions. Cancers (Basel) 2024; 16:4198. [PMID: 39766096 PMCID: PMC11674768 DOI: 10.3390/cancers16244198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/02/2024] [Accepted: 12/11/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Pancreatic cystic lesions (PCLs) are frequently detected incidentally and vary from benign to malignant. Accurate differentiation between mucinous (M-PCLs) and non-mucinous PCLs (NM-PCLs) is essential for appropriate management. This study aims to validate the accuracy of on-site glucose measurement using a glucometer with a cut-off of 50 mg/dL for distinguishing M-PCLs from NM-PCLs. METHODS In this prospective multicenter study, conducted at three European academic hospitals, patients who underwent endoscopic ultrasound-guided fine-needle aspiration for PCLs between 2019 and 2020 were included. On-site glucose measurement was performed using a conventional glucometer. Data on demographics, clinical features, EUS findings, and histopathology were collected. RESULTS Fifty patients were enrolled, with 37 having glucose levels < 50 mg/dL and 13 ≥ 50 mg/dL. M-PCLs were more common in the <50 mg/dL group (81%) compared to the ≥50 mg/dL group (23%, p < 0.001). The median CEA was higher in the <50 mg/dL group (146 ng/mL) than in the ≥50 mg/dL group (3 ng/mL, p = 0.047). On-site glucose testing < 50 mg/dl demonstrated a sensitivity of 93.2%, a specificity of 76.5%, and an accuracy of 89% for detecting M-PCLs with an AUC of 0.74 and an OR of 14.29 (p < 0.001). In comparison, CEA > 192 ng/mL had a sensitivity of 55.6%, a specificity of 87.5%, and an accuracy of 75.8% for M-PCLs, with an AUC of 0.65 and an OR of 4.44. CONCLUSIONS On-site glucose measurement using a glucometer with a cut-off of <50 mg/dL is a highly accurate, rapid, and cost-effective method for differentiating M-PCLs from NM-PCLs. Our results validate the glucose cut-off in a multicentric prospective cohort supporting its integration into standard diagnostic protocols for PCLs.
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Affiliation(s)
- Angelo Bruni
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola, 40138 Bologna, Italy; (A.B.); (C.R.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Leonardo Henry Eusebi
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola, 40138 Bologna, Italy; (A.B.); (C.R.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40138 Bologna, Italy; (A.L.); (P.F.)
| | - Claudio Ricci
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola, 40138 Bologna, Italy; (A.B.); (C.R.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Marcello Maida
- Department of Medicine and Surgery, University of Enna ‘Kore’, 94100 Enna, Italy;
- Gastroenterology Unit, Umberto I Hospital, 94100 Enna, Italy
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40138 Bologna, Italy; (A.L.); (P.F.)
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola, 40138 Bologna, Italy; (A.B.); (C.R.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Riadh Sadik
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg University, 413 45 Gothenburg, Sweden; (R.S.)
| | - Nico Pagano
- Gastroenterology Unit, Department of Oncological and Specialty Medicine, University Hospital Maggiore della Carità, 28100 Novara, Italy
| | - Per Hedenström
- Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg University, 413 45 Gothenburg, Sweden; (R.S.)
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola, 40138 Bologna, Italy; (A.B.); (C.R.); (G.B.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
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Millastre J, Hermoso-Durán S, de Solórzano MO, Fraunhoffer N, García-Rayado G, Vega S, Bujanda L, Sostres C, Lanas Á, Velázquez-Campoy A, Abian O. Thermal Liquid Biopsy: A Promising Tool for the Differential Diagnosis of Pancreatic Cystic Lesions and Malignancy Detection. Cancers (Basel) 2024; 16:4024. [PMID: 39682210 PMCID: PMC11640424 DOI: 10.3390/cancers16234024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/25/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
Pancreatic cystic lesions (PCLs) are a heterogeneous group of lesions with increasing incidence, usually identified incidentally on imaging studies (multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS)) [...].
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Affiliation(s)
- Judith Millastre
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain; (J.M.); (M.O.d.S.); (G.G.-R.); (C.S.); (Á.L.)
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
| | - Sonia Hermoso-Durán
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
- Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain;
| | - María Ortiz de Solórzano
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain; (J.M.); (M.O.d.S.); (G.G.-R.); (C.S.); (Á.L.)
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
| | - Nicolas Fraunhoffer
- Programa Franco-Argentino de Estudio del Cáncer de Páncreas, Buenos Aires, Argentina;
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM, CNRS UMR, Aix-Marseille Université, 13009 Marseille, France
- Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Equipe Labellisée La Ligue, 13288 Marseille, France
| | - Guillermo García-Rayado
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain; (J.M.); (M.O.d.S.); (G.G.-R.); (C.S.); (Á.L.)
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
| | - Sonia Vega
- Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, 50018 Zaragoza, Spain;
| | - Luis Bujanda
- Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain;
- Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain
| | - Carlos Sostres
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain; (J.M.); (M.O.d.S.); (G.G.-R.); (C.S.); (Á.L.)
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
| | - Ángel Lanas
- Service of Digestive Diseases, University Clinic Hospital Lozano Blesa, 50009 Zaragoza, Spain; (J.M.); (M.O.d.S.); (G.G.-R.); (C.S.); (Á.L.)
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
| | - Adrián Velázquez-Campoy
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
- Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain;
- Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, 50018 Zaragoza, Spain;
- Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, 50009 Zaragoza, Spain
| | - Olga Abian
- Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009 Zaragoza, Spain;
- Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain;
- Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, 50018 Zaragoza, Spain;
- Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, 50009 Zaragoza, Spain
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Rogowska J, Semeradt J, Durko Ł, Małecka-Wojciesko E. Diagnostics and Management of Pancreatic Cystic Lesions-New Techniques and Guidelines. J Clin Med 2024; 13:4644. [PMID: 39200786 PMCID: PMC11355509 DOI: 10.3390/jcm13164644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/01/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Pancreatic cystic lesions (PCLs) are increasingly diagnosed owing to the wide use of cross-sectional imaging techniques. Accurate identification of PCL categories is critical for determining the indications for surgical intervention or surveillance. The classification and management of PCLs rely on a comprehensive and interdisciplinary evaluation, integrating clinical data, imaging findings, and cyst fluid markers. EUS (endoscopic ultrasound) has become the widely used diagnostic tool for the differentiation of pancreatic cystic lesions, offering detailed evaluation of even small pancreatic lesions with high sensitivity and specificity. Additionally, endoscopic ultrasound-fine-needle aspiration enhances diagnostic capabilities through cytological analysis and the assessment of fluid viscosity, tumor glycoprotein concentration, amylase levels, and molecular scrutiny. These detailed insights play a pivotal role in improving the clinical prognosis and management of pancreatic neoplasms. This review will focus mainly on the latest recommendations for the differentiation, management, and treatment of pancreatic cystic lesions, highlighting their clinical significance.
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Affiliation(s)
- Jagoda Rogowska
- Department of Digestive Tract Diseases, Medical University of Lodz, 90-647 Lodz, Poland; (J.S.); (Ł.D.); (E.M.-W.)
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Olar MP, Iacobescu M, Bolboacă SD, Pojoga C, Moșteanu O, Seicean R, Rusu I, Banc O, Iuga CA, Seicean A. Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions. Int J Mol Sci 2024; 25:3224. [PMID: 38542201 PMCID: PMC10970073 DOI: 10.3390/ijms25063224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/02/2024] [Accepted: 03/09/2024] [Indexed: 04/04/2024] Open
Abstract
Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1β) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1β, glucose, and CEA, and serum for Ngal and IL-1β. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1β and serum Ngal made no diagnostic contribution.
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Affiliation(s)
- Miruna Patricia Olar
- Department of Gastroenterology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Victor Babeș Str., no. 8, 400012 Cluj-Napoca, Romania; (M.P.O.); (C.P.); (O.M.); (I.R.); (A.S.)
| | - Maria Iacobescu
- Research Center for Advanced Medicine MedFUTURE, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Str., nr. 4-6, 400349 Cluj-Napoca, Romania; (M.I.); (C.A.I.)
| | - Sorana D. Bolboacă
- Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Str., no. 6, 400349 Cluj-Napoca, Romania
| | - Cristina Pojoga
- Department of Gastroenterology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Victor Babeș Str., no. 8, 400012 Cluj-Napoca, Romania; (M.P.O.); (C.P.); (O.M.); (I.R.); (A.S.)
- Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., no. 19-21, 400162 Cluj-Napoca, Romania;
- International Institute for Advanced Study of Psychotherapy and Applied Mental Health, Department of Clinical Psychology and Psychotherapy, Babeș-Bolyai University, Sindicatelor Str., no. 7, 400029 Cluj-Napoca, Romania
| | - Ofelia Moșteanu
- Department of Gastroenterology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Victor Babeș Str., no. 8, 400012 Cluj-Napoca, Romania; (M.P.O.); (C.P.); (O.M.); (I.R.); (A.S.)
- Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., no. 19-21, 400162 Cluj-Napoca, Romania;
| | - Radu Seicean
- First Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Clinicilor Str., no. 3-5, 400006 Cluj-Napoca, Romania;
| | - Ioana Rusu
- Department of Gastroenterology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Victor Babeș Str., no. 8, 400012 Cluj-Napoca, Romania; (M.P.O.); (C.P.); (O.M.); (I.R.); (A.S.)
- Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., no. 19-21, 400162 Cluj-Napoca, Romania;
| | - Oana Banc
- Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., no. 19-21, 400162 Cluj-Napoca, Romania;
| | - Cristina Adela Iuga
- Research Center for Advanced Medicine MedFUTURE, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Str., nr. 4-6, 400349 Cluj-Napoca, Romania; (M.I.); (C.A.I.)
- Drug Analysis, Department Pharmacy 3, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Str., no. 6, 400349 Cluj-Napoca, Romania
| | - Andrada Seicean
- Department of Gastroenterology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Victor Babeș Str., no. 8, 400012 Cluj-Napoca, Romania; (M.P.O.); (C.P.); (O.M.); (I.R.); (A.S.)
- Regional Institute of Gastroenterology and Hepatology, Croitorilor Str., no. 19-21, 400162 Cluj-Napoca, Romania;
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Yip-Schneider MT, Muraru R, Kim RC, Wu HH, Sherman S, Gutta A, Al-Haddad MA, Dewitt JM, Schmidt CM. EUS-guided fine needle aspiration-based clues to mistaken or uncertain identity: serous pancreatic cysts. HPB (Oxford) 2023; 25:1587-1594. [PMID: 37749004 PMCID: PMC10843000 DOI: 10.1016/j.hpb.2023.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/21/2023] [Accepted: 09/05/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND/OBJECTIVES Pancreatic serous cystic neoplasms (SCN) present a diagnostic challenge given their increasing frequency of detection and benign nature yet relatively high rate of misdiagnosis. Here, imaging and analyses associated with EUS-guided fine-needle aspiration (EUS-FNA) are evaluated for their ability to provide a correct preoperative diagnosis of SCN. METHODS A surgical cohort with confirmed pathological diagnosis of SCN (n = 62) and a surveillance cohort with likely SCN (n = 31) were assessed for imaging (CT/MRI/EUS) and EUS-FNA-based analyses (cytology/DNA analysis for Von Hippel-Lindau [VHL] gene alterations/biomarkers). RESULTS In the surgical cohort, CT/MRI and EUS respectively predicted SCN in 4 of 58(7%) and 19 of 62(31%). Cyst fluid cytology and VHL alterations predicted SCN in 1 of 51(2%) and 5 of 21(24%), respectively. High specificity cyst fluid biomarkers (vascular endothelial growth factor [VEGF]/glucose/carcinoembryonic antigen [CEA]/amylase) correctly identified SCN in 25 of 27(93%). In the surveillance cohort, cyst fluid biomarkers predicted SCN in 12 of 12(100%) while VHL alterations identified SCN 3 of 10(30%). CONCLUSION High specificity cyst fluid biomarkers provided the most sensitive means of diagnosing SCN preoperatively. To obtain a preoperative diagnosis of SCN at the highest level of certainty, a multidisciplinary approach should be taken to inform appropriate SCN management.
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Affiliation(s)
- Michele T Yip-Schneider
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA.
| | - Rodica Muraru
- Center for Outcomes Research in Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Rachel C Kim
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Howard H Wu
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Stuart Sherman
- Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Aditya Gutta
- Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mohammad A Al-Haddad
- Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - John M Dewitt
- Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA.
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Carrara S, Fantin A, Khalaf K, Rizkala T, Koleth G, Andreozzi M, Spadaccini M, Colombo M, Gruppo M, Bonifacio C, Gavazzi F, Capretti GL, Ridolfi C, Nappo G, Spaggiari P, Tommaso LD, Sollai M, Zerbi A, Maselli R, Fugazza A, Hassan C, Facciorusso A, Repici A. Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions. Dig Liver Dis 2023; 55:1548-1553. [PMID: 37612214 DOI: 10.1016/j.dld.2023.08.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 07/07/2023] [Accepted: 08/03/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND AND AIMS Differentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs. METHODS We retrospectively analyzed 110 consecutive patients with PCLs from 2 Italian Hospitals who underwent EUS with H-Flow and EUS fine needle aspiration to obtain cystic fluid. The accuracy of fluid biomarkers was evaluated against morphological features on radiology and EUS. Gold standard for diagnosis was surgical resection. A clinical and radiological follow up was applied in those patients who were not resected because not surgical indication and no signs of malignancy were shown. RESULTS Of 110 patients, 65 were diagnosed with a mucinous cyst, 41 with a non-mucinous cyst, and 4 with an undetermined cyst. Fluid analysis alone yielded 76.7% sensitivity, 56.7% specificity, 77.8 positive predictive value (PPV), 55.3 negative predictive value (NPV) and 56% accuracy in diagnosing pancreatic cysts alone. Our composite method yielded 97.3% sensitivity, 77.1% specificity, 90.1% PPV, 93.1% NPV, 73.2% accuracy. CONCLUSIONS This new composite could be applied to the holistic approach of combining cyst morphology, vascularity, and fluid analysis alongside endoscopist expertise.
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Affiliation(s)
- Silvia Carrara
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy.
| | - Alberto Fantin
- Unit of Surgical Oncology of Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
| | - Kareem Khalaf
- Division of Gastroenterology, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Tommy Rizkala
- Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
| | - Glenn Koleth
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy
| | - Marta Andreozzi
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy
| | - Marco Spadaccini
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy
| | - Matteo Colombo
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy
| | - Mario Gruppo
- Unit of Surgical Oncology of Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
| | | | - Francesca Gavazzi
- Humanitas Research Hospital -IRCCS, Pancreatic Surgery Unit, Rozzano, Italy
| | | | - Cristina Ridolfi
- Humanitas Research Hospital -IRCCS, Pancreatic Surgery Unit, Rozzano, Italy
| | - Gennaro Nappo
- Humanitas Research Hospital -IRCCS, Pancreatic Surgery Unit, Rozzano, Italy
| | - Paola Spaggiari
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy
| | - Luca Di Tommaso
- Humanitas Research Hospital -IRCCS, Pathology Unit, Rozzano, Italy
| | - Mauro Sollai
- Humanitas Research Hospital -IRCCS, Pathology Unit, Rozzano, Italy
| | - Alessandro Zerbi
- Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy; Humanitas Research Hospital -IRCCS, Pancreatic Surgery Unit, Rozzano, Italy
| | - Roberta Maselli
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
| | | | - Cesare Hassan
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
| | - Antonio Facciorusso
- Section of Gastroenterology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Alessandro Repici
- Humanitas Research Hospital -IRCCS-, Endoscopy Unit, Rozzano, Italy; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
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Pflüger MJ, Jamouss KT, Afghani E, Lim SJ, Rodriguez Franco S, Mayo H, Spann M, Wang H, Singhi A, Lennon AM, Wood LD. Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and meta-analysis. Pancreatology 2023; 23:868-877. [PMID: 37230894 DOI: 10.1016/j.pan.2023.05.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 04/10/2023] [Accepted: 05/13/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts. METHODS We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC. RESULTS Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts. CONCLUSIONS Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
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Affiliation(s)
- Michael Johannes Pflüger
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery CCM|CVK, Charité, Universitätsmedizin Berlin, Germany; Graduate School of Life Sciences, Utrecht University, The Netherlands
| | - Kevin Tony Jamouss
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elham Afghani
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Su Jin Lim
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Harrison Mayo
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Marcus Spann
- Johns Hopkins University School of Medicine, Welch Medical Library, Baltimore, MD, USA
| | - Hao Wang
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Aatur Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| | - Anne Marie Lennon
- Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA.
| | - Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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8
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Sheik DA, Byers K, Thomas M, Rajesh UC, Ifuku K, Kirkwood K, Al-Haddad M, Craik CS, Davisson VJ. Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer. FRONTIERS IN GASTROENTEROLOGY (LAUSANNE, SWITZERLAND) 2023; 2:1258998. [PMID: 38846269 PMCID: PMC11156210 DOI: 10.3389/fgstr.2023.1258998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/09/2024]
Abstract
The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 μL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.
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Affiliation(s)
- Daniel A. Sheik
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | - Kaleb Byers
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | - Mini Thomas
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
| | | | - Kelli Ifuku
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Kimberly Kirkwood
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Mohammed Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University (IU) School of Medicine, Indianapolis, IN, United States
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, United States
| | - V. Jo Davisson
- Research and Technology Department, Amplified Sciences, Inc, West Lafayette, IN, United States
- Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy, West Lafayette, IN, United States
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9
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Ye M, Zhang B, Han X, Wei X, Wang Y, Cao W, Wu J, Chen C, Sun X, Sun K, Li H, Zhang Q, Liang T. Low-Pass Genomic Sequencing Reveals Novel Subtypes of Pancreatic Cystic Neoplasms. Ann Surg Oncol 2023; 30:5804-5812. [PMID: 37249723 DOI: 10.1245/s10434-023-13676-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 05/08/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND Over the years, the detection rate of pancreatic cystic neoplasms (PCNs) has significantly increased; however, the differential diagnosis and identification of high-risk PCNs remain challenging. We sought to investigate whether chromosomal instability (CIN) features in cell-free DNA in the cystic fluid of PCNs could help to identify high-risk PCNs. METHODS Pancreatic cystic fluid samples from 102 patients with PCNs were intraoperatively collected for detection of CIN using an ultrasensitive chromosomal aneuploidy detector. Clinical and imaging data were retrospectively collected, and statistical analysis was performed to assess the potential role of CIN in clinical practice. RESULTS CIN was investigated in a total of 100 patients. Sixteen of 26 serous cystic cystadenomas (SCAs) harbored deletions of chr3p and/or chr6p, whereas low rates of CIN were detected in mucinous cystic neoplasms. Most malignant PCNs presented with more than one type of CIN; amplification of chr1q and chr8q found in nine and seven of 11 malignant PCNs (81.8% and 63.6%), respectively, could aid in distinguishing high-risk IPMNs from low-risk ones, with a higher sensitivity than imaging. A combination of the mural nodule imaging feature and amplification of chr1q and chr8q achieved a sensitivity of 70.0% and a specificity of 82.4% in identifying high-risk IPMNs. CONCLUSIONS Our work revealed the distinct CIN signature of different types of PCNs. Deletions of chr3p and chr6p defined a subtype of SCAs. Gains of chr1q and chr8q were associated with insidious malignant PCNs and helped identify high-risk IPMNs.
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Affiliation(s)
- Mao Ye
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China
| | - Bo Zhang
- Department of General Surgery, Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Xu Han
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaobao Wei
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yangyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wanyue Cao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangchao Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Cao Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xu Sun
- Department of General Surgery, Huzhou Central Hospital, Zhejiang University School of Medicine, Huzhou, China
| | - Ke Sun
- Zhejiang University Cancer Center, Hangzhou, China
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haijun Li
- Department of General Surgery, Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Zhejiang University Cancer Center, Hangzhou, China.
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, Zhejiang Province, China.
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Zhejiang University Cancer Center, Hangzhou, China.
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, Zhejiang Province, China.
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10
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Kundu R, Rana SS, Suneel R, Dey P. EUS-guided FNAC in intra-abdominal lesions: Technique of tissue acquisition, ancillary testing, pearls and perils, and prospects. Diagn Cytopathol 2023. [PMID: 37154168 DOI: 10.1002/dc.25153] [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: 03/13/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/10/2023]
Abstract
Endoscopic ultrasound enables visualization of lesions within and in the vicinity of the gastrointestinal tract. Endoscopic ultrasound guided fine needle aspiration cytology (EUS-FNAC) helps in targeting various luminal and extraluminal lesions both diagnostically and therapeutically. Various intra-abdominal organs amenable to EUS-FNA include the gastrointestinal tract (GIT), pancreas, kidney, adrenal gland, liver, bile duct, gallbladder, spleen, and lymph nodes. EUS-FNAC is mostly done for pancreatic and intra-abdominal lymph nodal lesions. In the present review, we have discussed various aspects of EUS-FNAC.
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Affiliation(s)
- Reetu Kundu
- Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Surinder Singh Rana
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rachagiri Suneel
- Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranab Dey
- Department of Cytology and Gynecologic Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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11
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Caiazza F, Conroy PC, Ivry SL, York T, Lin J, Hernandez S, Hoffmann TJ, Francis SS, Park WG, Yip-Schneider MT, Schmidt CM, Brand R, Craik CS, Kirkwood K. Accurate Identification of Mucinous Pancreatic Cystic Lesions Using Small-Volume Analytes. J Surg Res 2023; 284:322-331. [PMID: 36369049 DOI: 10.1016/j.jss.2022.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 07/26/2022] [Accepted: 08/19/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION The accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only routinely used test, requires high volumes and has low sensitivity. We aimed to compare the performance of two investigational small-volume biomarkers, glucose and the protease gastricsin, to CEA for PCL classification. METHODS We obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs from four institutions between 2003 and 2016. Gastricsin activity was measured using an internally quenched fluorescent substrate. Glucose levels were measured with a standard glucometer. CEA levels were obtained from the medical record. Models using Classification and Regression Trees were created to predict mucinous status. Model performance was evaluated using nested cross-validation. RESULTS Gastricsin activity, CEA, and glucose levels from patients with mucinous (n = 50) and nonmucinous (n = 31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers (gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized [GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly improve AUC, with CEA + GVN (0.88) performing similarly to CEA + GPN (0.95), GVN + glucose (0.87), GPN + glucose (0.95), and CEA + glucose (0.84). The three-analyte combination performed similarly to single and dual classifiers (GPN + glucose + CEA AUC 0.95; GVN + glucose + CEA AUC 0.87). After multiple comparison corrections, there were no significant differences between the individual, dual, and triple classifiers. CONCLUSIONS Gastricsin and glucose performed similarly to CEA and required <5% of the volume required for CEA; these classifiers may be useful in patients with limited cyst fluid. Future multicenter prospective studies are needed to validate and compare these novel small-volume biomarkers.
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Affiliation(s)
- Francesco Caiazza
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California
| | - Patricia C Conroy
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Sam L Ivry
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California
| | - Tyler York
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Joseph Lin
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Sophia Hernandez
- Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Thomas J Hoffmann
- Department of Epidemiology & Biostatistics, and Institute for Human Genetics, University of California, San Francisco, San Francisco, California
| | - Stephen S Francis
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, California
| | - Walter G Park
- Department of Medicine, Division of Gastroenterology & Hepatology, Stanford University, Stanford, California
| | | | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Randall Brand
- Department of Medicine, Division of Gastroenterology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Charles S Craik
- Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California
| | - Kimberly Kirkwood
- Department of Surgery, University of California, San Francisco, San Francisco, California.
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12
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Li SY, Wang ZJ, Pan CY, Wu C, Li ZS, Jin ZD, Wang KX. Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions: A Network Meta-Analysis. Am J Gastroenterol 2023; 118:243-255. [PMID: 36563321 DOI: 10.14309/ajg.0000000000002088] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 11/02/2022] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. METHODS A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. RESULTS Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. DISCUSSION For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.
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Affiliation(s)
- Shi-Yu Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhi-Jie Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Cheng-Ye Pan
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Cheng Wu
- Department of Military Health Statistics, Naval Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Zhen-Dong Jin
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Kai-Xuan Wang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
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13
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Abstract
Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".
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Affiliation(s)
- Sahin Coban
- Department of Gastroenterology, Mount Auburn Hospital, 330 Mt Auburn St, Cambridge, MA 02138, USA.
| | - Omer Basar
- Department of Gastroenterology, The University of Missouri, Columbia, MO 65211, USA
| | - William R Brugge
- Department of Gastroenterology, Harvard Medical School, Mount Auburn Hospital, 330 Mt Auburn St, Cambridge, MA 02138, USA
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14
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Huang X, Feng Y, Ma D, Ding H, Dong G, Chen Y, Huang X, Zhang J, Xu X, Chen C. The molecular, immune features, and risk score construction of intraductal papillary mucinous neoplasm patients. Front Mol Biosci 2022; 9:887887. [PMID: 36090038 PMCID: PMC9459388 DOI: 10.3389/fmolb.2022.887887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/03/2022] [Indexed: 11/21/2022] Open
Abstract
Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precancerous lesion, with increasing incidence in recent years. However, the mechanisms of IPMN progression into invasive cancer remain unclear. The mRNA expression data of IPMN/PAAD patients were extracted from the TCGA and GEO databases. First, based on GSE19650, we analyzed the molecular alterations, tumor stemness, immune landscape, and transcriptional regulation of IPMN progression. The results indicated that gene expression changed dramatically, specifically at the intraductal papillary-mucinous adenoma (IPMA) stage. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Kyoto Encyclopedia of Genes and Genomes (GSEA) pathway analyses showed that glycoprotein-related, cell cycle, and P53 pathways displayed the most significant changes during progression. With IPMN progression, tumor stemness increased continuously, and KRAS, ERBB3, RUNX1, and ELF3 are essential driver genes affecting tumor stemness. Motif analysis suggested that KLF4 may be a specific transcription factor that regulates gene expression in the IPMA stage, while MYB and MYBL1 control gene expression in the IPMC and invasive stages, respectively. Then, GSE19650 and GSE71729 transcriptome data were combined to perform the least absolute shrinkage and selection operator (LASSO) method and Cox regression analysis to develop an 11-gene prediction model (KCNK1, FHL2, LAMC2, CDCA7, GPX3, C7, VIP, HBA1, BTG2, MT1E, and LYVE1) to predict the prognosis of pancreatic cancer patients. The reliability of the model was validated in the GSE71729 and TCGA databases. Finally, 11 additional IPMN patients treated in our hospital were included, and the immune microenvironment changes during IPMN progression were analyzed by immunohistochemistry (IHC). IHC results suggest that Myeloid-derived suppressor cells (MDSCs) and macrophages may be key in the formation of immunosuppressive microenvironment of IPMN progression. Our study deepens our understanding of IPMN progression, especially the changes in the immune microenvironment. The findings of this work may contribute to the development of new therapeutic strategies for IPMN.
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Affiliation(s)
- Xing Huang
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yipeng Feng
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China
- The Fourth Clinical College of Nanjing Medical University, Nanjing, China
| | - Dawei Ma
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Hanlin Ding
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China
- The Fourth Clinical College of Nanjing Medical University, Nanjing, China
| | - Gaochao Dong
- Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
- Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China
| | - Yan Chen
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaochen Huang
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Jingyuan Zhang
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Chen Chen, ; Xinyu Xu, ; Jingyuan Zhang,
| | - Xinyu Xu
- Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Chen Chen, ; Xinyu Xu, ; Jingyuan Zhang,
| | - Chen Chen
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Chen Chen, ; Xinyu Xu, ; Jingyuan Zhang,
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15
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Wietrzykowska-Grishanovich D, Pawlik E, Neubauer K. Biochemical Intracystic Biomarkers in the Differential Diagnosis of Pancreatic Cystic Lesions. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58080994. [PMID: 35893110 PMCID: PMC9331360 DOI: 10.3390/medicina58080994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/20/2022] [Accepted: 07/23/2022] [Indexed: 11/16/2022]
Abstract
Background and Objectives: Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also because of the aging of the population. PCLs comprise challenging clinical problems, as their manifestations vary from benign to malignant lesions. Therefore, the recognition of PCLs is achieved through a complex diagnostic and surveillance process, which in turn is usually long-term, invasive, and expensive. Despite the progress made in the identification of novel biomarkers in the cystic fluid that also support the differentiation of PCLs, their application in clinical practice is limited. Materials and Methods: We conducted a systematic review of the literature published in two databases, Pubmed and Embase, on biochemical biomarkers in PCLs that may be applied in the diagnostic algorithms of PCLs. Results: Eleven studies on intracystic glucose, twenty studies on intracystic carcinoembryonic antigen (CEA), and eighteen studies on other biomarkers were identified. Low levels of intracystic glucose had high sensitivity and specificity in the differentiation between mucinous and non-mucinous cystic neoplasms. Conclusions: CEA and glucose are the most widely studied fluid biochemical markers in pancreatic cystic lesions. Glucose has better diagnostic accuracy than CEA. Other biochemical biomarkers require further research.
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Affiliation(s)
- Dominika Wietrzykowska-Grishanovich
- Department of Gastroenterology and Hepatology, University Teaching Hospital, Borowska 213, 50-556 Wroclaw, Poland;
- Correspondence: (D.W.-G.); (K.N.)
| | - Ewa Pawlik
- Department of Gastroenterology and Hepatology, University Teaching Hospital, Borowska 213, 50-556 Wroclaw, Poland;
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
- Correspondence: (D.W.-G.); (K.N.)
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16
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Pușcașu CI, Rimbaş M, Mateescu RB, Larghi A, Cauni V. Advances in the Diagnosis of Pancreatic Cystic Lesions. Diagnostics (Basel) 2022; 12:diagnostics12081779. [PMID: 35892490 PMCID: PMC9394320 DOI: 10.3390/diagnostics12081779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/18/2022] [Accepted: 07/18/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic cystic lesions (PCLs) are a heterogenous group of lesions ranging from benign to malignant. There has been an increase in PCLs prevalence in recent years, mostly due to advances in imaging techniques, increased awareness of their existence and population aging. Reliable discrimination between neoplastic and non-neoplastic cystic lesions is paramount to ensuring adequate treatment and follow-up. Although conventional diagnostic techniques such as ultrasound (US), magnetic resonance imaging (MRI) and computer tomography (CT) can easily identify these lesions, assessing the risk of malignancy is limited. Endoscopic ultrasound (EUS) is superior to cross-sectional imaging in identifying potentially malignant lesions due to its high resolution and better imaging characteristics, and the advantage of allowing for cyst fluid sampling via fine-needle aspiration (FNA). More complex testing, such as cytological and histopathological analysis and biochemical and molecular testing of the aspirated fluid, can ensure an accurate diagnosis.
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Affiliation(s)
- Claudia Irina Pușcașu
- Gastroenterology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania; (C.I.P.); (R.B.M.)
| | - Mihai Rimbaş
- Gastroenterology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania; (C.I.P.); (R.B.M.)
- Department of Internal Medicine, Carol Davila University of Medicine, 050474 Bucharest, Romania
- Correspondence: ; Tel.: +40-723-232-052
| | - Radu Bogdan Mateescu
- Gastroenterology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania; (C.I.P.); (R.B.M.)
- Department of Internal Medicine, Carol Davila University of Medicine, 050474 Bucharest, Romania
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy;
| | - Victor Cauni
- Urology Department, Colentina Clinical Hospital, 020125 Bucharest, Romania;
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17
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Habib GM, Ramadan A, El-Ansary M, Abdellatif Z, El-Serafy M, Okasha H. Value of pancreatic cyst fluid SPINK1 and glucose in differentiating potentially malignant cysts from those of benign nature: A prospective cohort study. Saudi J Gastroenterol 2022; 28:348-354. [PMID: 35848704 PMCID: PMC9752528 DOI: 10.4103/sjg.sjg_81_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Diagnosis of malignant pancreatic cystic lesions (PCLs) is challenging as there is no investigation that offers both high diagnostic sensitivity and specificity for a definite diagnosis. Accurate diagnosis of cyst type is vital in order to not miss opportunities for early treatment of potentially malignant lesions and to avoid unnecessary surgeries. Serine protease inhibitor Kazal type I (SPINK1) and glucose are promising cyst fluid markers for differentiation of mucinous from non-mucinous cysts. We aim to validate the value of SPINK1 and glucose in detecting potentially malignant PCLs. METHODS A prospective study was conducted on 80 patients presenting with PCLs. Endoscopic ultrasound (EUS) evaluation of detailed cyst morphology and EUS with fine needle aspiration (FNA) were done. Fluid analysis for carcinoembryonic antigen (CEA), glucose and SPINK1 and cytopathology were done. We compared these data with the final diagnosis based on cytopathological and postoperative histopathological examination. RESULTS Cyst fluid SPINK1 was significantly higher in malignant or potentially malignant cysts compared to benign cysts (0.91 vs 0.47 ng/ml; P = 0.001). Also, glucose was significantly lower in malignant or potentially malignant cysts compared to benign cysts (21.5 vs 68.5 mg/dl; P = 0.0001). Glucose and SPINK1 had the best sensitivity and specificity for differentiating mucinous from non-mucinous cysts with 84.78% and 73.53% (AUC 0.76; 95% CI [0.65-0.88]; cutoff value = 42 mg/dl), and 70.59% and 65.22% (AUC 0.72; 95% CI [0.64-0.86]; cutoff value = 0.58 ug/L) respectively. CEA level >192 ng/ml, high SPINK1 level and lymph node enlargement were the independent predictors of malignant cysts. CONCLUSION Cyst fluid SPINK1 and glucose are promising diagnostic markers for the diagnosis of potentially malignant PCLs.
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Affiliation(s)
- Ghada M. Habib
- Department of Hepatology and Endemic Medicine, Cairo University, Cairo, Egypt,Address for correspondence: Dr. Ghada M. Habib, Hepatology and Gastroenterology at Kasr Al-Ainy School of Medicine, Cairo University, 130 3rd District, Al Hadaba Al Wosta, Mokattam, Cairo, Egypt. E-mail:
| | - Ahmed Ramadan
- Department of Hepatology and Endemic Medicine, Cairo University, Cairo, Egypt
| | - Mervat El-Ansary
- Department of Clinical Pathology, Cairo University, Cairo, Egypt
| | - Zeinab Abdellatif
- Department of Hepatology and Endemic Medicine, Cairo University, Cairo, Egypt
| | - Magdy El-Serafy
- Department of Hepatology and Endemic Medicine, Cairo University, Cairo, Egypt
| | - Hussein Okasha
- Department of Internal Medicine Division of Gastroenterology, Cairo University, Cairo, Egypt
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Okasha HH, Abdellatef A, Elkholy S, Mogawer MS, Yosry A, Elserafy M, Medhat E, Khalaf H, Fouad M, Elbaz T, Ramadan A, Behiry ME, Y William K, Habib G, Kaddah M, Abdel-Hamid H, Abou-Elmagd A, Galal A, Abbas WA, Altonbary AY, El-Ansary M, Abdou AE, Haggag H, Abdellah TA, Elfeki MA, Faheem HA, Khattab HM, El-Ansary M, Beshir S, El-Nady M. Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions. World J Gastrointest Endosc 2022; 14:402-415. [PMID: 35978716 PMCID: PMC9265252 DOI: 10.4253/wjge.v14.i6.402] [Citation(s) in RCA: 3] [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: 10/22/2021] [Revised: 11/28/2021] [Accepted: 05/05/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-β), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.
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Affiliation(s)
- Hussein Hassan Okasha
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Abeer Abdellatef
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Shaimaa Elkholy
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Mohamad-Sherif Mogawer
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Ayman Yosry
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Magdy Elserafy
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Eman Medhat
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Hanaa Khalaf
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Magdy Fouad
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Tamer Elbaz
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Ahmed Ramadan
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Mervat E Behiry
- Department of Internal Medicine, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
| | - Kerolis Y William
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Ghada Habib
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Mona Kaddah
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Haitham Abdel-Hamid
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Amr Abou-Elmagd
- Department of Gastroenterology, Armed forces College of Medicine, Cairo 11451, Egypt
| | - Ahmed Galal
- Endoscopy and Internal Medicine Consultant at Dr/Ahmed Galal Endoscopy Center, Alexandria 35516, Egypt
| | - Wael A Abbas
- Department of Internal Medicine, Faculty of Medicine, Assuit University, Assuit 71111, Egypt
| | | | - Mahmoud El-Ansary
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo 11451, Egypt
| | - Aml E Abdou
- Department of Microbiology and Immunology, Faculty of Medicine for girls Al-Azhar University, Cairo 11451, Egypt
| | - Hani Haggag
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Tarek Ali Abdellah
- Department of Internal Medicine, Faculty of Medicine, Ain shams University, Cairo 11451, Egypt
| | - Mohamed A Elfeki
- Department of Internal Medicine, Bani-suef University, Bani-suef, Bani-suef 62511, Egypt
| | - Heba Ahmed Faheem
- Department of Internal Medicine, Faculty of Medicine, Ain shams University, Cairo 11451, Egypt
| | - Hani M Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
| | - Mervat El-Ansary
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
| | - Safia Beshir
- Department of Environmental Medicine & Clinical Pathology, National Research Centre, Cairo 11451, Egypt
| | - Mohamed El-Nady
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
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Guzmán-Calderón E, Md BMM, Casellas JA, Aparicio JR. Intracystic Glucose Levels Appear Useful for Diagnosis of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis. Dig Dis Sci 2022; 67:2562-2570. [PMID: 34009555 DOI: 10.1007/s10620-021-07035-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 05/04/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) in the pancreatic cystic fluid is the most important biomarker for differentiating mucinous from non-mucinous pancreatic cystic lesions (PCLs). However, recent studies have shown that glucose levels in pancreatic cystic fluid can discriminate mucinous from non-mucinous cysts. AIMS To perform a meta-analysis to determine the utility of intracystic fluid glucose of pancreatic mucinous cysts compared with intracystic CEA. METHODS We conducted a systematic review of the literature in the PubMed, OVID Medline, and Cochrane databases. This meta-analysis considers studies published up to October 2020. RESULTS Six studies comprising 506 patients were selected; 61.2% of the population was female. Of the 480 PCLs, 287 (59.7%) were mucinous. Pooled sensitivity and specificity of cystic fluid glucose levels for mucinous PCLs were 91% and 85%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 6.33 and 0.11, respectively. Pooled diagnostic odds ratio (DOR) was 60.94. The pooled area under the summary receiver operating characteristic (SROC) curve was 0.959. Pooled sensitivity and specificity of pancreatic cystic fluid CEA levels were 61% and 93%. The PLR and NLR were 8.51 and 0.40, respectively. Pooled DOR was 23.52, and the pooled area under the SROC curve was 0.861. CONCLUSION Glucose has become a useful method and appears to be better than CEA for differentiating between mucinous PCLs and non-mucinous PCLs. We suggest that the analysis of glucose in PCLs be routinely performed for the differential diagnosis of these lesions.
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Affiliation(s)
- Edson Guzmán-Calderón
- Gastroenterology Unit of Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati s/n, Jesús María, Lima, Peru. .,Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru. .,Gastroenterology Unit of Angloamericana Clinic, Lima, Peru.
| | | | - Juan A Casellas
- Gastroenterology Unit Oh Hospital General Universitario de Alicante, Alicante, Spain
| | - José Ramón Aparicio
- Gastroenterology Unit Oh Hospital General Universitario de Alicante, Alicante, Spain
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Abstract
Andrew Canakis.
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Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA.
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Pancreatic cystic lesions. Differential diagnosis and treatment strategy. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2022; 87:188-197. [DOI: 10.1016/j.rgmxen.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/05/2021] [Indexed: 11/20/2022]
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Lira-Treviño A, Carranza Mendoza IG, Borbolla Arizti JP, Soriano-Ríos A, Uscanga-Domínguez L, Peláez-Luna M. Pancreatic cystic lesions. Differential diagnosis and treatment strategy. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:188-197. [PMID: 35610168 DOI: 10.1016/j.rgmx.2021.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 11/05/2021] [Indexed: 04/14/2025]
Abstract
The differential diagnosis of pancreatic cystic lesions (PCLs) includes non-neoplastic lesions and neoplastic epithelial lesions. Given that management is determined by the risk for malignant progression, associated symptoms, and other characteristics, an accurate diagnosis is imperative. The present review attempts to provide a critical path that facilitates the characterization and management of PCLs.
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Affiliation(s)
- A Lira-Treviño
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - A Soriano-Ríos
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - L Uscanga-Domínguez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - M Peláez-Luna
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; División de Investigación, Facultad de Medicina, UNAM, Mexico City, Mexico.
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Intracystic Glucose and Carcinoembryonic Antigen in Differentiating Histologically Confirmed Pancreatic Mucinous Neoplastic Cysts. Am J Gastroenterol 2022; 117:478-485. [PMID: 35034045 DOI: 10.14309/ajg.0000000000001623] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/29/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Differentiating mucinous neoplastic pancreatic cysts (MNPC) from cysts without malignant potential can be challenging. Guidelines recommend using fluid carcinoembryonic antigen (CEA) to differentiate MNPC; however, its sensitivity and specificity vary widely. Intracystic glucose concentration has shown promise in differentiating MNPC, but data are limited to frozen specimens and cohorts of patients without histologic diagnoses. This study aimed to compare glucose and CEA concentrations in differentiating MNPC using fresh fluid obtained from cysts with confirmatory histologic diagnoses. METHODS This multicenter cohort study consisted of patients undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cysts during January 2013-May 2020. Patients were included if the cyst exhibited a histologic diagnosis and if both CEA and glucose were analyzed from fresh fluid. Receiver operating curve (ROC) characteristics were analyzed, and various diagnostic parameters were compared. RESULTS Ninety-three patients, of whom 59 presented with MNPC, met the eligibility criteria. The area under the receiver operating curve (AUROC) was 0.96 for glucose and 0.81 for CEA (difference 0.145, P = 0.003). A CEA concentration of ≥192 ng/mL had sensitivity of 62.7% and specificity of 88.2% in differentiating MNPC, whereas glucose concentration of ≤25 mg/dL had sensitivity and specificity of 88.1% and 91.2%, respectively. DISCUSSION Intracystic glucose is superior to CEA concentration for differentiating MNPC when analyzed from freshly obtained fluid of cysts with histologic diagnoses. The advantage of glucose is augmented by its low cost and ease of implementation, and therefore, its widespread adoption should come without barriers. Glucose has supplanted CEA as the best fluid biomarker in differentiating MNPC.
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Mohan BP, Madhu D, Khan SR, Kassab LL, Ponnada S, Chandan S, Facciorusso A, Crino SF, Barresi L, McDonough S, Adler DG. Intracystic Glucose Levels in Differentiating Mucinous From Nonmucinous Pancreatic Cysts: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:e131-e136. [PMID: 33731599 DOI: 10.1097/mcg.0000000000001507] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 01/20/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Mucinous pancreatic cysts are well reported to transform into pancreatic adenocarcinoma, whereas nonmucinous cysts are mostly benign with low risk for malignant transformation. Nonsurgical methods of differentiating mucinous and nonmucinous pancreatic cysts are challenging and entail a multi investigational approach. Low intracystic glucose levels have been evaluated in multiple studies for its accuracy in differentiating mucinous from nonmucinous cysts of the pancreas. METHODS Multiple databases were searched and studies that reported on the utility of intracystic glucose levels in diagnosing mucinous pancreatic cysts were analyzed. Meta-analysis was conducted using the random-effects model, heterogeneity was assessed by I2%, and pooled diagnostic test accuracy values were calculated. RESULTS Seven studies were included in the analysis from an initial total of 375 citations. The pooled sensitivity of low glucose in differentiating mucinous pancreatic cyst was 90.5% [95% confidence interval (CI): 88.1-92.5; I2=0%] and the pooled specificity was 88% (95% CI: 80.8-92.7; I2=79%). The sensitivity at a glucose cut-off of 50 was 90.1% (95% CI: 87.2-92.5; I2=0%) and the specificity was 85.3% (95% CI: 76.8-91.1; I2=76%). The sensitivity of glucose levels in pancreatic cyst fluid taken by endoscopic ultrasound guided fine-needle aspiration was 90.8% (95% CI: 87.9-93.1; I2=0%) and the specificity was 90.5% (95% CI: 81.7-95.3; I2=83%). The sensitivity of point-of-care glucometers was 89.5% (95% CI: 87.9-93.1; I2=0%) and specificity was 83.9% (95% CI: 68.5-92.6; I2=43%). CONCLUSIONS Low glucose level at a cut-off of 50 mg/dL on fluid samples collected by endoscopic ultrasound guided fine-needle aspiration and analyzed by point-of-care glucometer achieves excellent diagnostic accuracy in differentiating mucinous pancreatic cysts.
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Affiliation(s)
- Babu P Mohan
- Department of Gastroenterology and Hepatology, University of Utah Health, Salt Lake City, UT
| | - Deepak Madhu
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palemo, Italy
| | - Shahab R Khan
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Lena L Kassab
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Suresh Ponnada
- Department of Internal Medicine, Roanoke Carilion Medical Center, Roanoke, VA
| | - Saurabh Chandan
- Department of Gastroenterology, CHI Creighton University Medical Center, Omaha, NE
| | | | - Stefano F Crino
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palemo, Italy
| | - Stephanie McDonough
- Department of Gastroenterology and Hepatology, University of Utah Health, Salt Lake City, UT
| | - Douglas G Adler
- Department of Gastroenterology and Hepatology, University of Utah Health, Salt Lake City, UT
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Nista EC, Schepis T, Candelli M, Giuli L, Pignataro G, Franceschi F, Gasbarrini A, Ojetti V. Humoral Predictors of Malignancy in IPMN: A Review of the Literature. Int J Mol Sci 2021; 22:12839. [PMID: 34884643 PMCID: PMC8657857 DOI: 10.3390/ijms222312839] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/21/2021] [Accepted: 11/23/2021] [Indexed: 02/05/2023] Open
Abstract
Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5-9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.
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Affiliation(s)
- Enrico C. Nista
- Department of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (E.C.N.); (T.S.); (L.G.); (A.G.)
| | - Tommaso Schepis
- Department of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (E.C.N.); (T.S.); (L.G.); (A.G.)
| | - Marcello Candelli
- Department of Emergency Medicine, Fondazione Policlinico Universitario, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.C.); (G.P.); (F.F.)
| | - Lucia Giuli
- Department of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (E.C.N.); (T.S.); (L.G.); (A.G.)
| | - Giulia Pignataro
- Department of Emergency Medicine, Fondazione Policlinico Universitario, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.C.); (G.P.); (F.F.)
| | - Francesco Franceschi
- Department of Emergency Medicine, Fondazione Policlinico Universitario, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.C.); (G.P.); (F.F.)
| | - Antonio Gasbarrini
- Department of Internal Medicine, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (E.C.N.); (T.S.); (L.G.); (A.G.)
| | - Veronica Ojetti
- Department of Emergency Medicine, Fondazione Policlinico Universitario, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.C.); (G.P.); (F.F.)
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Barutcuoglu B, Oruc N, Ak G, Kucukokudan S, Aydın A, Nart D, Harman M. Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions. Ann Clin Biochem 2021; 59:125-133. [PMID: 34719238 DOI: 10.1177/00045632211053998] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. METHODS Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic (n = 25), non-mucinous neoplastic (n = 20), mucinous neoplastic (n = 47) and pancreatic adenocarcinomas with cystic degeneration (n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. RESULTS Cyst fluid CEA and CA 19-9, levels were significantly higher (P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower (P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. CONCLUSIONS We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.
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Affiliation(s)
- Burcu Barutcuoglu
- Department of Clinical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Nevin Oruc
- Department of Gastroenterology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Güneş Ak
- Department of Clinical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Serdar Kucukokudan
- Department of Medical Biochemistry, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Ahmet Aydın
- Department of Gastroenterology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Deniz Nart
- Department of Pathology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
| | - Mustafa Harman
- Department of Radiology, 60521Ege University, Faculty of Medicine, Izmir, Turkey
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McCarty TR, Garg R, Rustagi T. Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. Gastrointest Endosc 2021; 94:698-712.e6. [PMID: 33964311 DOI: 10.1016/j.gie.2021.04.025] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/27/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Recently, low levels of intracystic glucose acquired with EUS-guided pancreatic cyst fluid sampling have been shown to help to differentiate mucinous from nonmucinous cystic neoplasms. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic characteristics of pancreatic cyst fluid glucose compared with carcinoembryonic antigen (CEA) for pancreatic cystic lesions. METHODS Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines and meta-analysis analyzed according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve for intracystic glucose or CEA alone or combination testing. RESULTS Eight studies (609 lesions; mean patient age, 63.56 ± 2.75 years; 60.36% women) were included. The pooled sensitivity for pancreatic cyst fluid glucose was significantly higher compared with CEA alone (91% [95% confidence interval {CI}, 88-94; I2 = .00] vs 56% [95% CI, 46-66; I2 = 537.14]; P < .001) with no difference in specificity (86% [95% CI, 81-90; I2 = 24.16] vs 96% [95% CI, 90-99; I2 = 38.06]; P > .05). Diagnostic accuracy was significantly higher for pancreatic cyst fluid glucose versus CEA alone (94% [95% CI, 91-96] vs 85% [95% CI, 82-88]; P < .001). Combination testing with pancreatic cyst fluid glucose and CEA did not improve the diagnostic accuracy compared with glucose alone (97% [95% CI, 95-98] vs 94% [95% CI, 91-96]; P > .05). CONCLUSIONS Low pancreatic cyst fluid glucose was associated with a high sensitivity and specificity with significantly improved diagnostic accuracy compared with CEA alone for the diagnosis of mucinous versus nonmucinous pancreatic cystic lesions.
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Affiliation(s)
- Thomas R McCarty
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rajat Garg
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Tarun Rustagi
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, USA
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Yip-Schneider MT, Wu H, Allison HR, Easler JJ, Sherman S, Al-Haddad MA, Dewitt JM, Schmidt CM. Biomarker Risk Score Algorithm and Preoperative Stratification of Patients with Pancreatic Cystic Lesions. J Am Coll Surg 2021; 233:426-434.e4. [PMID: 34166836 PMCID: PMC8403144 DOI: 10.1016/j.jamcollsurg.2021.05.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/28/2021] [Accepted: 05/28/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Pancreatic cysts are incidentally detected in up to 13% of patients undergoing radiographic imaging. Of the most frequently encountered types, mucin-producing (mucinous) pancreatic cystic lesions may develop into pancreatic cancer, while nonmucinous ones have little or no malignant potential. Accurate preoperative diagnosis is critical for optimal management, but has been difficult to achieve, resulting in unnecessary major surgery. Here, we aim to develop an algorithm based on biomarker risk scores to improve risk stratification. STUDY DESIGN Patients undergoing surgery and/or surveillance for a pancreatic cystic lesion, with diagnostic imaging and banked pancreatic cyst fluid, were enrolled in the study after informed consent (n = 163 surgical, 67 surveillance). Cyst fluid biomarkers with high specificity for distinguishing nonmucinous from mucinous pancreatic cysts (vascular endothelial growth factor [VEGF], glucose, carcinoembryonic antigen [CEA], amylase, cytology, and DNA mutation) were selected. Biomarker risk scores were used to design an algorithm to predict preoperative diagnosis. Performance was tested using surgical (retrospective) and surveillance (prospective) cohorts. RESULTS In the surgical cohort, the biomarker algorithm outperformed the preoperative clinical diagnosis in correctly predicting the final pathologic diagnosis (91% vs 73%; p < 0.000001). Specifically, nonmucinous serous cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) were correctly classified more frequently by the algorithm than clinical diagnosis (96% vs 30%; p < 0.000008 and 92% vs 69%; p = 0.04, respectively). In the surveillance cohort, the algorithm predicted a preoperative diagnosis with high confidence based on a high biomarker score and/or consistency with imaging from ≥1 follow-up visits. CONCLUSIONS A biomarker risk score-based algorithm was able to correctly classify pancreatic cysts preoperatively. Importantly, this tool may improve initial and dynamic risk stratification, reducing overdiagnosis and underdiagnosis.
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Affiliation(s)
- Michele T Yip-Schneider
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Simon Cancer Center, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - Huangbing Wu
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | | | - Jeffrey J Easler
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - Stuart Sherman
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - Mohammad A Al-Haddad
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN
| | - John M Dewitt
- Department of Medicine, Division of Gastroenterology, Indianapolis, IN
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; Biochemistry/Molecular Biology, Indianapolis, IN; Walther Oncology Center, Indianapolis, IN; Indiana University Simon Cancer Center, Indianapolis, IN; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN.
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Comparative analysis of glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis. Gastrointest Endosc 2021; 94:235-247. [PMID: 33852901 DOI: 10.1016/j.gie.2021.03.935] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 03/31/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis. METHODS We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted. RESULTS For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.76-0.83), and areas under the ROC curve of .96 and .79, respectively. Glucose had a higher sensitivity (90%), with uncommon false-negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust. CONCLUSION Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first-line test, particularly in small cysts with a limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis.
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O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol 2021; 27:4045-4087. [PMID: 34326612 PMCID: PMC8311531 DOI: 10.3748/wjg.v27.i26.4045] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).
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Affiliation(s)
- Robert S O'Neill
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
| | - Alina Stoita
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
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Confer BD, Iqbal U, Diehl DL. Comparison of pancreatic cystic fluid glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts. Gastrointest Endosc 2021; 94:201-202. [PMID: 34148575 DOI: 10.1016/j.gie.2021.02.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 02/23/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Bradley D Confer
- Department of Gastroenterology, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Umair Iqbal
- Department of Gastroenterology, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - David L Diehl
- Department of Gastroenterology, Geisinger Medical Center, Danville, Pennsylvania, USA
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Sun L, Huang H, Jin Z. Application of EUS-based techniques in the evaluation of pancreatic cystic neoplasms. Endosc Ultrasound 2021; 10:230-240. [PMID: 34213426 PMCID: PMC8411565 DOI: 10.4103/eus-d-20-00216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 03/21/2021] [Indexed: 12/04/2022] Open
Abstract
Pancreatic cystic neoplasms (PCNs) are being detected increasingly frequently due to the widespread use of high-resolution abdominal imaging modalities. Some subtypes of PCNs have the potential for malignant transformation. Therefore, accurate diagnosis of PCNs is crucial to determine whether surgical resection or surveillance is the best management strategy. However, the current cross-section imaging modalities are not accurate enough to enable definite diagnoses. In the last decade, EUS-based techniques have emerged, aiming to overcome the limitations of standard cross-section imaging modalities. These novel EUS-based techniques were primarily designed to acquire distinct images to make radiological diagnoses, collect cyst fluid to undergo biochemical or molecular analyses, and obtain tissue to conclude the pathological diagnoses. In this article, we present a comprehensive and critical review of these emerging EUS techniques for the diagnosis of PCNs, with emphasis being placed on the advantages, feasibilities, diagnostic performances, and limitations of these novel techniques.
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Affiliation(s)
- Liqi Sun
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Haojie Huang
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Zhendong Jin
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China
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Noia JL, Mejuto R, Oria I, De la Iglesia-García D, Villaverde A, Voces A, Pizzala J, Iglesias-García J, Urgiles D, Marcolongo M, Mazza O, Dominguez-Muñoz E. Rapid diagnosis of mucinous cystic pancreatic lesions by on-site cyst fluid glucometry. Surg Endosc 2021; 36:2473-2479. [PMID: 33988771 DOI: 10.1007/s00464-021-08532-9] [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: 02/09/2021] [Accepted: 04/30/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Available intracystic biomarkers show a limited accuracy for characterizing cystic pancreatic lesions (CPL). Glucose is an attractive alternative due to its availability, low cost and the possibility of on-site quantification by glucometry. AIM To evaluate the diagnostic accuracy of on-site glucometry from samples obtained by EUS-FNA in the differential diagnosis between mucinous from non-mucinous CPL. METHODS Retrospective, multicentre, cross-sectional study of patients who underwent EUS-FNA of a CPL. A derivation and a validation cohorts were evaluated. Intracystic glucose was quantified by on-site glucometry and colorimetry in the lab. Final diagnosis was based on surgical specimens or global evaluation of clinical and imaging data, cytology and intracystic CEA. Diagnostic accuracy was based on Receiver Operating Curve (ROC) curve analysis. Intraclass correlation coefficient (ICC) between on-site and lab glucose levels was calculated. RESULTS Seventy two patients were finally analysed (40 in the derivation cohort and 32 in the validation cohort). Intracystic glucose levels by on-site glucometry was 12.3 ± 28.2 mg/dl for mucinous CPL and 103.3 ± 58.2 mg/dl for non-mucinous CPL, p < 0.001. For an optimal cut-off point of 73 mg/dl, on-site glucose had a sensitivity, specificity, and positive and negative predictive value for the diagnosis of mucinous CPL of 0.89, 0.90, 0.94, 0.82 respectively in the derivation cohort, and 1.0, 0.71, 0.91, 1.0 respectively in the validation cohort. Correlation of on-site and lab glucose quantification was very high (ICC = 0.98). CONCLUSION On-site glucometry is a feasible, accurate and reproducible method for the characterization of CPL after EUS-FNA. It shows an excellent correlation with laboratory glucose values. Registration number: 2019/612.
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Affiliation(s)
- José Lariño Noia
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain.
| | - Rafael Mejuto
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain
| | - Inés Oria
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Daniel De la Iglesia-García
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain
| | - Augusto Villaverde
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Alba Voces
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain
| | - Juan Pizzala
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Julio Iglesias-García
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain
| | - Dalila Urgiles
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Mariano Marcolongo
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Oscar Mazza
- Department of Gastroenterology and Hepatology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, Health Research Institute of Santiago (IDIS), University Hospital of Santiago de Compostela, C/Choupana s/n, 15706, Santiago de Compostela, Spain
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Herranz Pérez R, de la Morena López F, Majano Rodríguez PL, Molina Jiménez F, Vega Piris L, Santander Vaquero C. Molecular analysis of pancreatic cystic neoplasm in routine clinical practice. World J Gastrointest Endosc 2021; 13:56-71. [PMID: 33623640 PMCID: PMC7890406 DOI: 10.4253/wjge.v13.i2.56] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 12/22/2020] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts.
AIM To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.
METHODS An 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy.
RESULTS Of the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of KRAS and/or GNAS showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05).
CONCLUSION Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.
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Affiliation(s)
- Raquel Herranz Pérez
- Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain
| | - Felipe de la Morena López
- Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain
| | - Pedro L Majano Rodríguez
- Molecular Biology Laboratory, Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain
| | - Francisca Molina Jiménez
- Molecular Biology Laboratory, Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain
| | - Lorena Vega Piris
- Methodological Support Unit, Department of Statistical Analysis, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, CP Madrid, Madrid 28006, Spain
| | - Cecilio Santander Vaquero
- Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid 28006, Spain
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Kane LE, Mellotte GS, Conlon KC, Ryan BM, Maher SG. Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration. Cancers (Basel) 2021; 13:769. [PMID: 33673153 PMCID: PMC7918773 DOI: 10.3390/cancers13040769] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 01/27/2021] [Accepted: 02/09/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PC) is regarded as one of the most lethal malignant diseases in the world, with GLOBOCAN 2020 estimates indicating that PC was responsible for almost half a million deaths worldwide in 2020. Pancreatic cystic lesions (PCLs) are fluid-filled structures found within or on the surface of the pancreas, which can either be pre-malignant or have no malignant potential. While some PCLs are found in symptomatic patients, nowadays many PCLs are found incidentally in patients undergoing cross-sectional imaging for other reasons-so called 'incidentalomas'. Current methods of characterising PCLs are imperfect and vary hugely between institutions and countries. As such, there is a profound need for improved diagnostic algorithms. This could facilitate more accurate risk stratification of those PCLs that have malignant potential and reduce unnecessary surveillance. As PC continues to have such a poor prognosis, earlier recognition and risk stratification of PCLs may lead to better treatment protocols. This review will focus on the importance of biomarkers in the context of PCLs and PCand outline how current 'omics'-related work could contribute to the identification of a novel integrated biomarker profile for the risk stratification of patients with PCLs and PC.
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Affiliation(s)
- Laura E. Kane
- Department of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin D08 W9RT, Ireland;
| | - Gregory S. Mellotte
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24 NR0A, Ireland; (G.S.M.); (B.M.R.)
| | - Kevin C. Conlon
- Discipline of Surgery, School of Medicine, Trinity College Dublin, Dublin D02 PN40, Ireland;
| | - Barbara M. Ryan
- Department of Gastroenterology, Tallaght University Hospital, Dublin D24 NR0A, Ireland; (G.S.M.); (B.M.R.)
| | - Stephen G. Maher
- Department of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin D08 W9RT, Ireland;
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Balaban VD, Cazacu IM, Pinte L, Jinga M, Bhutani MS, Saftoiu A. EUS-through-the-needle microbiopsy forceps in pancreatic cystic lesions: A systematic review. Endosc Ultrasound 2021; 10:19-24. [PMID: 32611848 PMCID: PMC7980686 DOI: 10.4103/eus.eus_23_20] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 04/09/2020] [Indexed: 12/16/2022] Open
Abstract
Pancreatic cystic lesions (PCLs) are being increasingly encountered in clinical practice, and sometimes, they can represent a diagnostic challenge. Recently, a through-the-needle micro forceps biopsy (MFB) device was introduced in the endosonography practice to facilitate EUS-guided sampling of PCLs. The aim was to perform a systematic review of studies evaluating the technical aspects, safety, and efficacy of the EUS-guided MFB for PCLs. A literature search was performed in three major databases, PubMed, Embase, and Web of Science in September 2019 using the search terms: "through-the-needle," "biopsy forceps," "microforceps," "endoscopic ultrasound," and "endosonography." Case reports and case series with <10 patients were excluded from the analysis. Altogether nine studies reporting on 463 patients were included in our systematic review. The mean age of the patients was 68.3 years, with a slight female predominance (60.9%). Most of the cysts were located in the body/tail of the pancreas (61.2%), with an overall mean size of 33 mm. The technical success of EUS-guided MFB was reported in 98.5%. The tissue acquisition yield reported was 88.2%, and the diagnostic accuracy was 68.6%. Adverse events were reported in 9.7%. EUS-guided MFB is technically feasible, safe, and has a high diagnostic accuracy for PCLs.
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Affiliation(s)
- Vasile Daniel Balaban
- Internal Medicine and Gastroenterology Clinic, “Carol Davila” University of Medicine and Pharmacy, Craiova, Romania
- Department of Gastroenterology, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania
| | - Irina M. Cazacu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Craiova, Romania
- Department of Gastroenterology, Hepatology and Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| | - Larisa Pinte
- Department of Internal Medicine, Colentina Clinical Hospital, Bucharest, Romania
| | - Mariana Jinga
- Internal Medicine and Gastroenterology Clinic, “Carol Davila” University of Medicine and Pharmacy, Craiova, Romania
- Department of Gastroenterology, “Dr. Carol Davila” Central Military Emergency University Hospital, Bucharest, Romania
| | - Manoop S. Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| | - Adrian Saftoiu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Craiova, Romania
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Faias S, Cravo M, Pereira da Silva J, Chaves P, Dias Pereira A. Endoscopic ultrasound with fine needle aspiration is useful in pancreatic cysts smaller than 3 cm. BMC Gastroenterol 2020; 20:413. [PMID: 33297971 PMCID: PMC7727209 DOI: 10.1186/s12876-020-01565-9] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 11/30/2020] [Indexed: 12/28/2022] Open
Abstract
Background In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation).
Objective To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. Methods Retrospective study of PCLs < 3 cm (2007–2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed.
Results We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging—AUC = 0.80 versus AUC = 60. Conclusion EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.
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Affiliation(s)
- Sandra Faias
- Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal. .,Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.
| | - Marília Cravo
- Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal.,Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - João Pereira da Silva
- Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - Paula Chaves
- Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.,Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - A Dias Pereira
- Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
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Simons-Linares CR, Yadav D, Lopez R, Bhatt A, Jang S, El-Khider F, Sanaka M, Stevens T, Vargo J, Chahal P. The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts. Pancreatology 2020; 20:1386-1392. [PMID: 32919884 DOI: 10.1016/j.pan.2020.08.024] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/21/2020] [Accepted: 08/30/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. METHODS A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. RESULTS 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). CONCLUSION Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).
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Affiliation(s)
- C Roberto Simons-Linares
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Divya Yadav
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Rocio Lopez
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Amit Bhatt
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Sunguk Jang
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Faris El-Khider
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Madhusudan Sanaka
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Tyler Stevens
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - John Vargo
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Prabhleen Chahal
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
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Ribaldone DG, Bruno M, Gaia S, Cantamessa A, Bragoni A, Caropreso P, Sacco M, Fagoonee S, Saracco GM, De Angelis C. Differential diagnosis of pancreatic cysts: A prospective study on the role of intra-cystic glucose concentration. Dig Liver Dis 2020; 52:1026-1032. [PMID: 32675041 DOI: 10.1016/j.dld.2020.06.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 06/20/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The accuracy and costs of current diagnostic methods in the differential diagnosis of pancreatic cystic lesions still has ample room for improvement. AIMS The aim of the study was to confirm the diagnostic yield of intracystic glucose in the diagnosis of pancreatic cyst subtypes. METHODS We prospectively recruited all patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration of pancreatic cyst at our Institution. RESULTS Fifty-six patients were included in the study. We found that intracystic glucose concentration < 50 mg/dL was significantly more sensitive than a concentration of Carcinoembryonic Antigen > 192 ng/mL (93.6% vs 54.8%; p = 0.003) for the diagnosis of mucinous cysts. In terms of specificity, the two markers were not different (96% vs 100%; p = 1). Regarding the diagnosis of non-mucinous cysts, intracystic glucose concentration ≥ 50 mg/mL showed higher sensitivity than Carcinoembryonic Antigen level < 5 ng/mL (96% vs 72%) although a statistical significance could not be reached (p = 0.07). The two markers were not statistically different in terms of specificity (93.6% vs 87.1%; p = 0.62). CONCLUSION Given its diagnostic performance and ease of measurement, intracystic glucose may replace Carcinoembryonic Antigen in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.
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Affiliation(s)
| | - Mauro Bruno
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Silvia Gaia
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Alessandro Cantamessa
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Alberto Bragoni
- Department of Laboratory Medicine, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Paola Caropreso
- Department of Laboratory Medicine, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Marco Sacco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy; Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Centre, 10126 Turin, Italy
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Claudio De Angelis
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.
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40
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Advances in the management of pancreatic cystic neoplasms. Curr Probl Surg 2020; 58:100879. [PMID: 34144739 DOI: 10.1016/j.cpsurg.2020.100879] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/09/2020] [Indexed: 12/11/2022]
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41
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Faias S, Pereira L, Roque R, Chaves P, Torres J, Cravo M, Pereira AD. Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts. Dig Dis Sci 2020; 65:2071-2078. [PMID: 31705344 DOI: 10.1007/s10620-019-05936-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/02/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described. AIMS To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis. MATERIALS AND METHODS In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological. RESULTS We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis. CONCLUSION Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.
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Affiliation(s)
- Sandra Faias
- Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal. .,Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.
| | - Luisa Pereira
- Center of Mathematics and Applications (CMA-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal
| | - Ruben Roque
- Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - Paula Chaves
- Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal.,Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - Joana Torres
- Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal
| | - Marília Cravo
- Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal.,Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - A Dias Pereira
- Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
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Mamone G, Barresi L, Tropea A, Di Piazza A, Miraglia R. MRI of mucinous pancreatic cystic lesions: a new updated morphological approach for the differential diagnosis. Updates Surg 2020; 72:617-637. [PMID: 32462610 DOI: 10.1007/s13304-020-00800-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 05/12/2020] [Indexed: 12/21/2022]
Abstract
Pancreatic cystic lesions (PCLs) have been increasingly identified over the past 2 decades due to the widespread use of high-resolution non-invasive abdominal imaging. They cover a vast spectrum, from benign to malignant and invasive lesions, thus they constitute a significant clinical entity. Among PCLs, mucin-producing lesions are those at risk of progression to malignancy. They include mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN). The diagnosis and management of these cystic lesions are a dilemma since there is a significant overlap in the morphology of benign and premalignant lesions. At the moment, there is no single test that will allow a correct diagnosis in all cases. Magnetic resonance (MR) and endoscopic ultrasound (EUS) morphology, with cyst fluid analysis and cytohistology done with EUS-guided procedure are the best techniques that can narrow the differential diagnosis and identify potentially malignant lesions requiring resection from those requiring follow-up only. The purpose of this paper is to present an updated review of MR imaging findings of mucinous PCLs and to provide a new morphological approach that can serve as a practical guide for the diagnosis of these lesions, allowing a more confident characterization and avoiding relevant misdiagnosis. Furthermore, we provide some information about EUS and cystic fluid analysis and cytohistology, since they are diagnostic modalities that radiologists and surgeons should be familiar with.
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Affiliation(s)
- Giuseppe Mamone
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), via Tricomi 5, 90127, Palermo, Italy.
| | - Luca Barresi
- Endoscopic Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Alessandro Tropea
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Ambra Di Piazza
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), via Tricomi 5, 90127, Palermo, Italy
| | - Roberto Miraglia
- Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), via Tricomi 5, 90127, Palermo, Italy
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de la Fuente J, Majumder S. Molecular Diagnostics and Testing for Pancreatic Cysts. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2020; 18:158-171. [PMID: 31989386 DOI: 10.1007/s11938-020-00270-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW In current clinical practice, the diagnosis and management of pancreatic cystic lesions (PCLs) are based on guidelines that combine clinical and imaging findings. These guidelines usefully identify a large category of low-risk PCLs that do not require treatment. However, they have limited accuracy for diagnosis of advanced neoplasia in worrisome and high-risk PCLs. Novel molecular markers that can accurately detect advanced neoplasia in PCLs can transform the care of patients with PCLs. We reviewed the recent medical literature on molecular diagnostics of PCLs and summarized molecular biomarkers assayed in cyst fluid, pancreatic juice, and blood. RECENT FINDINGS Several studies have been recently published describing promising early results in genetic, epigenetic, and protein biomarkers from cyst fluid to help in both histologic diagnosis and detection of advanced neoplasia. The majority of studies have been completed using opportunistically collected archival cyst fluid and few report validation in independent sample sets. Results of ongoing multicenter prospective validation studies are awaited and will help define the best combination of cyst fluid molecular markers. In multifocal PCLs communicating with the pancreatic ductal system, a pancreatic juice biomarker is likely to be less invasive and more informative. Novel biomarkers in pancreatic juice and blood are in early phases of study. SUMMARY The field of molecular diagnostic biomarkers for PCLs is rapidly evolving with several promising candidate markers being prospectively evaluated. In the near future, these novel molecular markers, combined with advances in imaging technology, will transform clinical decision-making in the management of PCLs and improve patient outcomes.
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Affiliation(s)
- Jaime de la Fuente
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA
| | - Shounak Majumder
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Sciences, 200 First St SW, Rochester, MN, 55905, USA.
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44
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Hao S, Takahashi C, Snyder RA, Parikh AA. Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future. Int J Mol Sci 2020; 21:ijms21031147. [PMID: 32050465 PMCID: PMC7037360 DOI: 10.3390/ijms21031147] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/04/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022] Open
Abstract
A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.
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Affiliation(s)
- Scarlett Hao
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Caitlin Takahashi
- Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; (S.H.); (C.T.)
| | - Rebecca A. Snyder
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
| | - Alexander A. Parikh
- Division of Surgical Oncology, Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA;
- Correspondence: ; Tel.: +1-252-744-4110
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45
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Pancreatic cystic neoplasms: current and future approaches to identify patients at risk. JOURNAL OF PANCREATOLOGY 2019. [DOI: 10.1097/jp9.0000000000000033] [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] Open
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van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 2019; 16:676-689. [PMID: 31527862 DOI: 10.1038/s41575-019-0195-x] [Citation(s) in RCA: 153] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/31/2019] [Indexed: 12/11/2022]
Abstract
Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed.
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Affiliation(s)
- Nadine C M van Huijgevoort
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
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Carmicheal J, Patel A, Dalal V, Atri P, Dhaliwal AS, Wittel UA, Malafa MP, Talmon G, Swanson BJ, Singh S, Jain M, Kaur S, Batra SK. Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s). Biochim Biophys Acta Rev Cancer 2019; 1873:188318. [PMID: 31676330 DOI: 10.1016/j.bbcan.2019.188318] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/25/2019] [Accepted: 10/25/2019] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an increased likelihood of future pancreatic cancer in patients placing them in a high-risk category. Discerning concurrent malignancy and risk of future PCL progression to cancer must be carefully and accurately determined to improve survival outcomes and avoid unnecessary morbidity of pancreatic resection. Unfortunately, current image-based guidelines are inadequate to distinguish benign from malignant lesions. There continues to be a need for accurate molecular and imaging biomarker(s) capable of identifying malignant PCLs and predicting the malignant potential of PCLs to enable risk stratification and effective intervention management. This review provides an update on the current status of biomarkers from pancreatic cystic fluid, pancreatic juice, and seromic molecular analyses and discusses the potential of radiomics for differentiating PCLs harboring cancer from those that do not.
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Affiliation(s)
- Joseph Carmicheal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Asish Patel
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Vipin Dalal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Pranita Atri
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Amaninder S Dhaliwal
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Uwe A Wittel
- Department of General- and Visceral Surgery, University of Freiburg Medical Center, Faculty of Medicine, Freiburg, Germany
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Geoffrey Talmon
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Benjamin J Swanson
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shailender Singh
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
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Ivry SL, Knudsen GM, Caiazza F, Sharib JM, Jaradeh K, Ravalin M, O’Donoghue AJ, Kirkwood KS, Craik CS. The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts. Biol Chem 2019; 400:1629-1638. [DOI: 10.1515/hsz-2019-0103] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/27/2019] [Indexed: 12/15/2022]
Abstract
Abstract
Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers.
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Affiliation(s)
- Sam L. Ivry
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
- Pharmaceutical Sciences and Pharmacogenomics Graduate Program , University of California , San Francisco, San Francisco, CA , USA
| | - Giselle M. Knudsen
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Francesco Caiazza
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Jeremy M. Sharib
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Katrin Jaradeh
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Matthew Ravalin
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Anthony J. O’Donoghue
- Skaggs School of Pharmacy and Pharmaceutical Chemistry , University of California , San Diego, La Jolla, CA , USA
| | - Kimberly S. Kirkwood
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
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Lopes CV. Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts. World J Gastroenterol 2019; 25:2271-2278. [PMID: 31148899 PMCID: PMC6529890 DOI: 10.3748/wjg.v25.i19.2271] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 03/30/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cystic lesions (PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts (pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions, it is imperative to identify mucinous cysts (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen (CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.
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Affiliation(s)
- César Vivian Lopes
- Department of Gastroenterology and Digestive Endoscopy, Santa Casa Hospital, Porto Alegre 91410-000, Brazil
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Raman A, Lennon AM. Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas. Visc Med 2018; 34:178-181. [PMID: 30140682 DOI: 10.1159/000490137] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Pancreatic cysts are common, and are identified in 2-13% of individuals undergoing cross-sectional imaging. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are pancreatic cysts which are precursors to pancreatic adenocarcinoma. Currently available tools are imperfect at differentiating IPMNs and MCNs from other, benign types of pancreatic cysts. The role of molecular markers in the evaluation of pancreatic cysts and the identification of cysts with high-grade dysplasia or invasive adenocarcinoma is reviewed.
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Affiliation(s)
- Aadhithya Raman
- Department of Medicine, Surgery, Radiology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anne Marie Lennon
- Department of Medicine, Surgery, Radiology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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