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Jafarnezhad-Ansariha F, Contran N, Cristofori C, Simonato M, Davanzo V, Moz S, Galozzi P, Fogar P, Nordi E, Padoan A, Aita A, Fassan M, Fantin A, Sartori A, Sperti C, Correani A, Carnielli V, Cogo P, Basso D. Cystic Fluid Total Proteins, Low-Density Lipoprotein Cholesterol, Lipid Metabolites, and Lymphocytes: Worrisome Biomarkers for Intraductal Papillary Mucinous Neoplasms. Cancers (Basel) 2025; 17:643. [PMID: 40002238 PMCID: PMC11853297 DOI: 10.3390/cancers17040643] [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: 12/30/2024] [Revised: 02/06/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration.
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Affiliation(s)
- Fahimeh Jafarnezhad-Ansariha
- Department of Surgery, Oncology and Gastroenterology-DISCOG, University of Padua, 35128 Padua, Italy; (F.J.-A.); (C.S.)
| | - Nicole Contran
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
| | - Chiara Cristofori
- Department of Gastroenterology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy; (C.C.); (A.F.)
| | - Manuela Simonato
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
- Pediatric Research Institute “Citta’ della Speranza”, Critical Care Biology and PCare Laboratories, 35127 Padua, Italy;
| | - Veronica Davanzo
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
| | - Stefania Moz
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
| | - Paola Galozzi
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
| | - Paola Fogar
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
| | - Evelyn Nordi
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
| | - Andrea Padoan
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
| | - Ada Aita
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
| | - Matteo Fassan
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
| | - Alberto Fantin
- Department of Gastroenterology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy; (C.C.); (A.F.)
| | - Anna Sartori
- Pediatric Research Institute “Citta’ della Speranza”, Critical Care Biology and PCare Laboratories, 35127 Padua, Italy;
| | - Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology-DISCOG, University of Padua, 35128 Padua, Italy; (F.J.-A.); (C.S.)
| | - Alessio Correani
- Department of Odontostomatologic and Specialized Clinical Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (A.C.); (V.C.)
| | - Virgilio Carnielli
- Department of Odontostomatologic and Specialized Clinical Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (A.C.); (V.C.)
- Division of Neonatology, Mother and Child Department, G. Salesi University Hospital, 60123 Ancona, Italy
| | - Paola Cogo
- Department of Medicine, Division of Pediatrics, S. Maria della Misericordia University Hospital, University of Udine, 33100 Udine, Italy;
| | - Daniela Basso
- Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy; (N.C.); (V.D.); (S.M.); (P.F.); (E.N.); (A.P.); (A.A.); (D.B.)
- Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (M.S.); (M.F.)
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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] [Download PDF] [Figures] [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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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:874-995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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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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Scheyda-Yoo K, Hofer U, Várnai-Händel A, Maus MKH, Dumoulin FL. [Rapid growth and malignant transformation of a mucinous cystic neoplasm during pregnancy - a case report]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1048-1052. [PMID: 38657617 DOI: 10.1055/a-2239-7898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
BACKGROUND Mucinous-cystic neoplasms (MCN) account for 10% of all pancreatic cystic lesions. They are found almost exclusively in females. MCN have an ovarian-like stroma and often estrogen and progesterone receptors. During pregnancy, they can massively increase in size and transform into malignancy. CASE REPORT We report on a 29-year-old woman in whom a 35mm cyst in the pancreatic tail had been diagnosed several years ago. After workup the lesions had been classified as a pseudocyst. During pregnancy, the cyst massively increased in size and finally was resected. Histology showed a mucinous-cystic neoplasia with focal malignant transformation. CONCLUSION Cystic neoplasms of the pancreas require a differentiated management. While overtreatment should be avoided, malignant transformation always merits consideration - in particular if the cystic lesion is located in the pancreatic tail. Women with suspected MCN or cystic pancreatic lesions of uncertain etiology should be informed about the (rare) risk of a malignant transformation of an MCN and should be closely monitored during pregnancy.
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Affiliation(s)
- Katharina Scheyda-Yoo
- Abteilung für Innere Medizin, Gemeinschaftskrankenhaus St Elisabeth St Petrus St Johannes gGmbH, Bonn, Germany
| | - Ulrich Hofer
- Abteilung für Radiologie, Interventionelle Radiologie und Neuroradiologie, Gemeinschaftskrankenhaus St Elisabeth St Petrus St Johannes gGmbH, Bonn, Germany
| | | | - Martin K-H Maus
- Funktionelle OGI Chirurgie, Evangelisches Krankenhaus Kalk, Koln, Germany
| | - Franz Ludwig Dumoulin
- Abteilung für Innere Medizin, Gemeinschaftskrankenhaus St Elisabeth St Petrus St Johannes gGmbH, Bonn, Germany
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Seyfedinova SS, Freylikhman OA, Sokolnikova PS, Samochernykh KA, Kostareva AA, Kalinina OV, Solonitsyn EG. Fine-needle aspiration technique under endoscopic ultrasound guidance: A technical approach for RNA profiling of pancreatic neoplasms. World J Gastrointest Oncol 2024; 16:2663-2672. [PMID: 38994174 PMCID: PMC11236257 DOI: 10.4251/wjgo.v16.i6.2663] [Citation(s) in RCA: 1] [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: 12/26/2023] [Revised: 02/18/2024] [Accepted: 04/07/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) has been a longstanding challenge. The prognosis of patients with PDAC depends on the stage at diagnosis. It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis. Most molecular studies are done using paraffin-embedded blocks; however, the integrity of DNA and RNA is often compromised in this format. Moreover, RNA isolated from human pancreatic tissue samples is generally of low quality, in part, because of the high concentration of endogenous pancreatic RNAse activity present. AIM To assess the potential of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling, including next-generation sequencing (NGS). METHODS Thirty-four EUS-FNA samples were included in this study: PDAC (n = 15), chronic pancreatitis (n = 5), pancreatic cysts (n = 14), mucinous cysts (mucinous cystic neoplasia/intraductal papillary mucinous neoplasia) n = 7, serous cystic neoplasms n = 5, and pseudocysts n = 2. Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy (TTNB). Samples were stored at -80 °C until analysis. RNA purity (A260/230, A260/280 ratios), concentration, and integrity (RIN) were assessed. Real-time polymerase chain reaction was conducted on all samples, and small RNA libraries were prepared from solid mass samples. RESULTS RNA was successfully extracted from 29/34 (85%) EUS-FNA samples: 100% pancreatic adenocarcinoma samples, 100% chronic pancreatitis samples, 70% pancreatic fluid cyst samples, and 50% TTNB samples. The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples (n = 29) including low-quality RNA specimens. Low concentration and nonoptimal RIN values (no less than 3) of RNA extracted from EUS-FNA samples did not prevent NGS library preparation. The suitability of cyst fluid samples for RNA profiling varied. The quality of RNA extracted from mucinous cyst fluid had a median RIN of 7.7 (5.0-8.2), which was compatible with that from solid neoplasms [6.2 (0-7.8)], whereas the quality of the RNA extracted from all fluids of serous cystic neoplasms and TTNB samples had a RIN of 0. CONCLUSION The results demonstrate the high potential of EUS-FNA material for RNA profiling of various pancreatic lesions, including low-quality RNA specimens.
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Affiliation(s)
| | | | - Polina Sergeevna Sokolnikova
- Research Laboratory of Molecular and Cellular Modeling and Gene Therapy, Almazov Medical Research Centre, Saint-Petersburg 197341, Russia
| | - Konstantin Aleksandrovich Samochernykh
- Head of Russian Neurosurgical Institute Named after Prof. A. L. Polenova, Russian Neurosurgical Institute Named after Prof. A. L. Polenova, Saint-Petersburg 191014, Russia
| | - Anna Aleksandrovna Kostareva
- Head of Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
| | - Olga Viktorovna Kalinina
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
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Seyfedinova SS, Freylikhman OA, Sokolnikova PS, Samochernykh KA, Kostareva AA, Kalinina OV, Solonitsyn EG. Fine-needle aspiration technique under endoscopic ultrasound guidance: A technical approach for RNA profiling of pancreatic neoplasms. World J Gastrointest Oncol 2024; 16:2651-2660. [DOI: 10.4251/wjgo.v16.i6.2651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 02/18/2024] [Accepted: 04/07/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) has been a longstanding challenge. The prognosis of patients with PDAC depends on the stage at diagnosis. It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis. Most molecular studies are done using paraffin-embedded blocks; however, the integrity of DNA and RNA is often compromised in this format. Moreover, RNA isolated from human pancreatic tissue samples is generally of low quality, in part, because of the high concentration of endogenous pancreatic RNAse activity present.
AIM To assess the potential of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling, including next-generation sequencing (NGS).
METHODS Thirty-four EUS-FNA samples were included in this study: PDAC (n = 15), chronic pancreatitis (n = 5), pancreatic cysts (n = 14), mucinous cysts (mucinous cystic neoplasia/intraductal papillary mucinous neoplasia) n = 7, serous cystic neoplasms n = 5, and pseudocysts n = 2. Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy (TTNB). Samples were stored at -80 °C until analysis. RNA purity (A260/230, A260/280 ratios), concentration, and integrity (RIN) were assessed. Real-time polymerase chain reaction was conducted on all samples, and small RNA libraries were prepared from solid mass samples.
RESULTS RNA was successfully extracted from 29/34 (85%) EUS-FNA samples: 100% pancreatic adenocarcinoma samples, 100% chronic pancreatitis samples, 70% pancreatic fluid cyst samples, and 50% TTNB samples. The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples (n = 29) including low-quality RNA specimens. Low concentration and nonoptimal RIN values (no less than 3) of RNA extracted from EUS-FNA samples did not prevent NGS library preparation. The suitability of cyst fluid samples for RNA profiling varied. The quality of RNA extracted from mucinous cyst fluid had a median RIN of 7.7 (5.0-8.2), which was compatible with that from solid neoplasms [6.2 (0-7.8)], whereas the quality of the RNA extracted from all fluids of serous cystic neoplasms and TTNB samples had a RIN of 0.
CONCLUSION The results demonstrate the high potential of EUS-FNA material for RNA profiling of various pancreatic lesions, including low-quality RNA specimens.
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Affiliation(s)
| | | | - Polina Sergeevna Sokolnikova
- Research Laboratory of Molecular and Cellular Modeling and Gene Therapy, Almazov Medical Research Centre, Saint-Petersburg 197341, Russia
| | - Konstantin Aleksandrovich Samochernykh
- Head of Russian Neurosurgical Institute Named after Prof. A. L. Polenova, Russian Neurosurgical Institute Named after Prof. A. L. Polenova, Saint-Petersburg 191014, Russia
| | - Anna Aleksandrovna Kostareva
- Head of Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
| | - Olga Viktorovna Kalinina
- Research Laboratory of Autoimmune and Autoinflammatory Diseases, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russia
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Gopakumar H, Puli SR. Value of Endoscopic Ultrasound-Guided Through-the-Needle Biopsy in Pancreatic Cystic Lesions. A Systematic Review and Meta-Analysis. J Gastrointest Cancer 2024; 55:15-25. [PMID: 37341913 DOI: 10.1007/s12029-023-00949-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND AND AIM Endoscopic ultrasound-guided through-the-needle biopsy (EUS-TTNB) has been used over the past few years to increase diagnostic accuracy for pancreatic cystic lesions (PCLs). However, many concerns remain regarding its widespread use. This systematic review and meta-analysis aimed to pool the data from high-quality studies to evaluate the utility of EUS-TTNB in diagnosing PCLs. METHODS Electronic databases (PubMed, Embase, and Cochrane Library) from January 2010 through October 2022 were searched for publications addressing the diagnostic performance of EUS-TTNB in the diagnosis of pancreatic cystic lesions. Pooled proportions were calculated using fixed (inverse variance) and random-effects (DerSimonian-Laird) models. RESULTS The initial search identified 635 studies, of which 35 relevant articles were reviewed. We extracted data from 11 studies that met the inclusion criterion, comprising a total of 575 patients. Mean patient age was 62.25 years ± 6.12 with females constituting 61.39% of the study population. Pooled sensitivity of EUS-TTNB in differentiating a PCL as neoplastic or non-neoplastic was 76.60% (95% CI = 72.60-80. 30). For the same indication, EUS TTNB had a pooled specificity of 98.90% (95% CI = 93.80-100.00). The positive likelihood ratio was 10.28 (95% CI = 4.77-22.15), and the negative likelihood ratio was 0.26 (95% CI = 0.22-0.31). The pooled diagnostic odds ratio for EUS-TTNB in diagnosing PCLs as malignant/pre-malignant vs. non-malignant was 41.34 (95% CI = 17.42-98.08). Pooled adverse event rates were 3.04% (95% CI = 1.83-4.54) for pancreatitis, 4.02% (95% CI = 2.61-5.72) for intra-cystic bleeding, 0.94% (95% CI = 0.33-1.86) for fever, and 1.73% (95% CI = 0.85-2.91) for other minor events. CONCLUSIONS EUS-TTNB has good sensitivity with excellent specificity in accurately classifying PCLs as neoplastic or non-neoplastic. Adding EUS-TTNB to EUS-FNA increases the accuracy of EUS-guided approach in diagnosing PCLs. However, it could significantly increase the risk of post-procedural pancreatitis.
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Affiliation(s)
- Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, USA.
| | - Srinivas R Puli
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, USA
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Benke M, Zeöld A, Kittel Á, Khamari D, Hritz I, Horváth M, Keczer B, Borka K, Szücs Á, Wiener Z. MiR-200b categorizes patients into pancreas cystic lesion subgroups with different malignant potential. Sci Rep 2023; 13:19820. [PMID: 37963969 PMCID: PMC10646105 DOI: 10.1038/s41598-023-47129-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 11/09/2023] [Indexed: 11/16/2023] Open
Abstract
Extracellular vesicles (EV) carry their cargo in a membrane protected form, however, their value in early diagnostics is not well known. Although pancreatic cysts are heterogeneous, they can be clustered into the larger groups of pseudocysts (PC), and serous and mucinous pancreatic cystic neoplasms (S-PCN and M-PCN, respectively). In contrast to PCs and S-PCNs, M-PCNs may progress to malignant pancreatic cancers. Since current diagnostic tools do not meet the criteria of high sensitivity and specificity, novel methods are urgently needed to differentiate M-PCNs from other cysts. We show that cyst fluid is a rich source of EVs that are positive and negative for the EV markers CD63 and CD81, respectively. Whereas we found no difference in the EV number when comparing M-PCN with other pancreatic cysts, our EV-based biomarker identification showed that EVs from M-PCNs had a higher level of miR-200b. We also prove that not only EV-derived, but also total cyst fluid miR-200b discriminates patients with M-PCN from other pancreatic cysts with a higher sensitivity and specificity compared to other diagnostic methods, providing the possibility for clinical applications. Our results show that measuring miR-200b in cyst fluid-derived EVs or from cyst fluid may be clinically important in categorizing patients.
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Affiliation(s)
- Márton Benke
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Anikó Zeöld
- Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
| | - Ágnes Kittel
- Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
- HUN-REN Institute of Experimental Medicine, Budapest, Hungary
| | - Delaram Khamari
- Department of Genetics, Cell and Immunobiology, and HUN-REN-SU Translational Extracellular Vesicle Research Group, Semmelweis University, Budapest, Hungary
| | - István Hritz
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Miklós Horváth
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Bánk Keczer
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Katalin Borka
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Ákos Szücs
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary.
| | - Zoltán Wiener
- Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
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10
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Cheung TT, Lee YT, Tang RSY, She WH, Cheng KC, Cheung CC, Chiu KWH, Chok KSH, Chow WS, Lai TW, Seto WK, Yau T. The Hong Kong consensus recommendations on the diagnosis and management of pancreatic cystic lesions. Hepatobiliary Surg Nutr 2023; 12:715-735. [PMID: 37886207 PMCID: PMC10598309 DOI: 10.21037/hbsn-22-471] [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] [Received: 10/07/2022] [Accepted: 02/10/2023] [Indexed: 10/28/2023]
Abstract
Background The finding of pancreatic cystic lesions (PCL) on incidental imaging is becoming increasingly common. International studies report a prevalence of 2.2-44.7% depending on the population, imaging modality and indication for imaging, and the prevalence increases with age. Patients with PCL are at risk of developing pancreatic cancer, a disease with a poor prognosis. This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency (PEI) from a group of local specialists. Methods Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022. The expert panel included gastroenterologists, hepatobiliary surgeons, oncologists, radiologists, and endocrinologists. Results Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions. They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient. Where indicated, patients should undergo pancreatectomy to excise PCL. Following pancreatectomy, patients are at risk of PEI, leading to gastrointestinal dysfunction and malnutrition. Therefore, such patients should be monitored for symptoms of PEI, and promptly treated with pancreatic enzyme replacement therapy (PERT). Patients with poor response to PERT may require increases in dose, addition of a proton pump inhibitor, and/or further investigation, including tests for pancreatic function. Patients are also at risk of new-onset diabetes mellitus after pancreatectomy; they should be screened and treated with insulin if indicated. Conclusions These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.
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Affiliation(s)
- Tan-To Cheung
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Yuk Tong Lee
- Gastroenterologist in private practice, Hong Kong, China
| | - Raymond Shing-Yan Tang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Kai Chi Cheng
- Department of Surgery, Kwong Wah Hospital, Hong Kong, China
| | | | - Keith Wan Hang Chiu
- Department of Radiology & Imaging, Queen Elizabeth Hospital, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Wing Sun Chow
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tak Wing Lai
- Department of Surgery, Princess Margaret Hospital, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Thomas Yau
- Department of Medicine, The University of Hong Kong, Hong Kong, China
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11
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van Huijgevoort NCM, Halfwerk HBG, Lekkerkerker SJ, Reinten RJ, Ramp F, Fockens P, Besselink MG, Busch OR, van Noesel CJM, van de Vijver MJ, Verheij J, van Hooft JE, Dijk F. Detecting KRAS mutations in pancreatic cystic neoplasms: droplet digital PCR versus targeted next-generation sequencing. HPB (Oxford) 2023; 25:155-159. [PMID: 36328896 DOI: 10.1016/j.hpb.2022.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 10/04/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Nadine C M van Huijgevoort
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Hans B G Halfwerk
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Selma J Lekkerkerker
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Roy J Reinten
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Frederique Ramp
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Carel J M van Noesel
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Marc J van de Vijver
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Joanne Verheij
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Frederike Dijk
- Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.
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12
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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13
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Oyedeji O, Rodgers S, Wrubel A, Shah R, Husain S. Pancreatic lymphoepithelial cyst with concurrent HIV infection: A case report and review of the literature. SAGE Open Med Case Rep 2022; 10:2050313X221131166. [PMID: 36274859 PMCID: PMC9580076 DOI: 10.1177/2050313x221131166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/19/2022] [Indexed: 11/15/2022] Open
Abstract
Pancreatic lymphoepithelial cysts are rare, benign, non-neoplastic unilocular or multilocular cystic lesions. These circumscribed pancreatic lesions are filled with keratinous material grossly and exhibit distinct microscopic features. Pancreatic lymphoepithelial cysts are like the more common lymphoepithelial cysts of the parotid glands, which have been associated with the diffuse infiltrative lymphocytosis syndrome often seen in patients with HIV infection. However, pancreatic lymphoepithelial cysts are rare and their association with HIV infection has not been established. The presence of secondary changes in non-neoplastic cysts such as goblet cell metaplasia that was present in our case is an important feature to be included in the differential diagnosis and not to be interpreted as a mucinous neoplasm, particularly on fine-needle aspiration specimen microscopic evaluation that would impact further management. Here we describe the diagnosis and treatment of lymphoepithelial cysts in a patient who was on highly active antiretroviral therapy for HIV infection and we provide a brief literature review. Defining the clinical characteristics of lymphoepithelial cysts in patients with HIV and determining accurate preoperative diagnostic procedures will be critical for establishing effective surgical and medical approaches to treating these cysts, which differ substantially from other more serious pancreatic cystic lesions.
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Affiliation(s)
- Oluwayomi Oyedeji
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI, USA,Oluwayomi Oyedeji, Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
| | - Shannon Rodgers
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI, USA
| | - Allen Wrubel
- Department of Diagnostic Radiology, Henry Ford Hospital, Detroit, MI, USA
| | - Rupen Shah
- Division of Surgical Oncology, Department of Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Sanam Husain
- Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI, USA
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14
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Pan S, Liu J, Guo J, Zhu Q, Wang L, Shi X. The clinical impact of endoscopic ultrasound-guided fine-needle aspiration on the patients with low-risk pancreatic cystic lesions. Front Oncol 2022; 12:961293. [PMID: 35992791 PMCID: PMC9389355 DOI: 10.3389/fonc.2022.961293] [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: 06/04/2022] [Accepted: 07/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background and aimsEndoscopic ultrasound (EUS) is playing a more and more important role in the management of pancreatic cystic lesion (PCLs). The aim of our study was to evaluate the clinical impact of EUS and EUS guided fine needle aspiration (FNA) on patients with low-risk PCLs.Materials and methodsLow-risk PCL patients who underwent EUS-FNA in 2 edoscopic centers were retrospectively collected and analyzed. The clinical impact of EUS-FNA on these patients was analyzed and the predictors for significance EUS-FNA (defined by diagnosis and treatment method change, new high-risk feature identified after imaging scans) were analyzed by logistic regression analyses.ResultsFrom July 2004 to February 2017, 186 patients with low-risk PCLs were included. The study cohort had a mean age of 52.4 ± 15.9 years (range: 19-86 years) with 89 (47.8%) male patients included. The clinical significance of EUS-FNAs was observed in 74 patients (39.8%). The presumed diagnoses of PCLs by imaging were changed in 51 (51/74, 68.9%) patients. Nineteen (19/74, 25.7%) new high-risk features were identified by EUS-FNA, and four patients (4/74, 5.4%) underwent surgery due to suspicious or malignant cytology. Based on multivariate analysis, large cyst size [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.02–1.19, P = 0.033], young age (OR: 0.94, 95% CI: 0.91–0.99, P = 0.041) and BMI over 25 (OR: 3.15, 95% CI: 1.29–7.86, P = 0.013) were independent predictors of clinical significance for EUS-FNA. The optimal age and cyst size to predict significance EUS-FNA was 46.0 years and 2.3cm.ConclusionsOn the basis of a 2-center retrospective study, EUS-FNA was clinically significant in about 40% of low-risk PCLs, especially in young, large cyst size, and overweight patients.
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Affiliation(s)
- Shubo Pan
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital, Jiangsu, China
| | - Jie Liu
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital, Jiangsu, China
| | - Jiefang Guo
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Qilin Zhu
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital, Jiangsu, China
| | - Liangjing Wang
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital, Jiangsu, China
| | - Xiaohua Shi
- Department of Gastroenterology, Suzhou Science and Technology Town Hospital, Jiangsu, China
- *Correspondence: Xiaohua Shi,
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15
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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: 11] [Impact Index Per Article: 3.7] [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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16
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Chidambaram S, Kawka M, Gall TM, Cunningham D, Jiao LR. Can we predict the progression of premalignant pancreatic cystic tumors to ductal adenocarcinoma? Future Oncol 2022; 18:2605-2612. [PMID: 35730473 DOI: 10.2217/fon-2021-1545] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent malignant pancreatic tumor. Few studies have shown how often PDACs arise from cystic precursor lesions. This special report aims to summarize the evidence on the progression of precancerous lesions to PDAC. A review of the literature found four studies that discussed pancreatic intraepithelial lesions (PanINs), three that discussed mucinous cystic neoplasms (MCN) and five that discussed intraductal papillary neoplasms (IPMNs). PanINs were the most common precursors lesion, with approximately 80% of PDACs originating from this lesion. The lack of evidence characterizing the features of PDAC precursor cystic lesions potentially leads to a subset of patients undergoing surgery unnecessarily. Advancements in molecular techniques could allow the study of cystic lesions at a genetic level, leading to more personalized management.
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Affiliation(s)
- Swathikan Chidambaram
- Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College, London, W12 0HS, UK
- Imperial College London, Exhibition Road, South Kensington, London, SW7 2BU, UK
| | - Michal Kawka
- Imperial College London, Exhibition Road, South Kensington, London, SW7 2BU, UK
| | - Tamara Mh Gall
- Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College, London, W12 0HS, UK
- Imperial College London, Exhibition Road, South Kensington, London, SW7 2BU, UK
| | - David Cunningham
- Department of Academic Surgery, The Royal Marsden Hospital, 203 Fulham Road, London, SW3 6JJ, UK
| | - Long R Jiao
- Imperial College London, Exhibition Road, South Kensington, London, SW7 2BU, UK
- Department of Academic Surgery, The Royal Marsden Hospital, 203 Fulham Road, London, SW3 6JJ, UK
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17
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Liu J, Xing Y, Sun L. Commentary: The Tumor Markers and Blood Inflammation Markers Are More Likely to Be the Indicators for Differentiating Benign and Malignant Pancreatic Mucinous Cystic Neoplasms. Front Oncol 2022; 12:901010. [PMID: 35720014 PMCID: PMC9200991 DOI: 10.3389/fonc.2022.901010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/16/2022] [Indexed: 11/30/2022] Open
Affiliation(s)
- Jiang Liu
- Department of Gastroenterology, Huzhou Hospital of Zhejiang University, Affiliated Central Hospital Huzhou University, Huzhou, China
| | - Ying Xing
- Department of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou, China
| | - Liqi Sun
- Department of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou, China
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18
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Gorris M, Janssen QP, Besselink MG, van den Broek BLJ, van Eijck CHJ, van Gils MJ, Koerkamp BG, Struik F, van Driel LMJW, van Hooft JE. Sensitivity of CT, MRI, and EUS-FNA/B in the preoperative workup of histologically proven left-sided pancreatic lesions. Pancreatology 2022; 22:136-141. [PMID: 34857486 DOI: 10.1016/j.pan.2021.11.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Left-sided pancreatic lesions are often treated surgically. Accurate diagnostic work-up is therefore essential to prevent futile major abdominal surgery. Large series focusing specifically on the preoperative work-up of left-sided pancreatic lesions are lacking. This surgical cohort analysis describes the sensitivity of CT, MRI, and EUS-FNA/B in the diagnostic work-up of left-sided pancreatic lesions. METHODS We performed a post-hoc analysis of patients who underwent surgery for a left-sided pancreatic lesion between April 2010 and August 2017 and participated in the randomized CPR trial. Primary outcome was the sensitivity of CT, MRI, and EUS-FNA/B. Sensitivity was determined as the most likely diagnosis of each modality compared with the postoperative histopathological diagnosis. Additionally, the change in sensitivity of EUS versus EUS-FNA/B (i.e., cyst fluid analysis, and/or tissue acquisition) was measured. RESULTS Overall, 181 patients were included (benign: 23%, premalignant: 27%, malignant: 50%). Most patients had solid lesions (65%). Preoperative imaging included CT (86%), MRI (41%), EUS (68%). Overall, CT and EUS-FNA/B reached a sensitivity of both 71%, compared with 66% for MRI. When EUS was combined with FNA/B, sensitivity rose from 64% to 71%. For solid lesions, CT reached the highest sensitivity (75%) when compared with MRI (70%) and EUS-FNA/B (69%). For cystic lesions, EUS-FNA/B reached the highest sensitivity (75%) when compared with CT and MRI (both 62%). CONCLUSIONS CT is the most sensitive diagnostic modality for solid and EUS-FNA/B for cystic left-sided pancreatic lesions. EUS-FNA/B was associated with an increased sensitivity when compared to EUS alone.
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Affiliation(s)
- Myrte Gorris
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands; Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
| | - Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Bram L J van den Broek
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Marjon J van Gils
- Department of Radiology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Femke Struik
- Department of Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
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19
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Jabłońska B, Szmigiel P, Mrowiec S. Pancreatic intraductal papillary mucinous neoplasms: Current diagnosis and management. World J Gastrointest Oncol 2021; 13:1880-1895. [PMID: 35070031 PMCID: PMC8713311 DOI: 10.4251/wjgo.v13.i12.1880] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) represent approximately 1% of all pancreatic neoplasms and 25% of cystic neoplasms. They are divided into three types: main duct-IPMN (MD-IPPMN), branch duct-IPMN (BD-IPMN), and mixed type-IPMN. In this review, diagnostics, including clinical presentation and radiological investigations, were described. Magnetic resonance imaging is the most useful for most IPMNs. Management depends on the type and radiological features of IPMNs. Surgery is recommended for MD-IPMN. For BD-IPMN, management involves surgery or surveillance depending on the tumor size, cyst growth rate, solid components, main duct dilatation, high-grade dysplasia in cytology, the presence of symptoms (jaundice, new-onset diabetes, pancreatitis), and CA 19.9 serum level. The patient's age and comorbidities should also be taken into consideration. Currently, there are different guidelines regarding the diagnosis and management of IPMNs. In this review, the following guidelines were presented: Sendai International Association of Pancreatology guidelines (2006), American Gastroenterological Association guidelines, revised international consensus Fukuoka guidelines (2012), revised international consensus Fukuoka guidelines (2017), and European evidence-based guidelines according to the European Study Group on Cystic Tumours of the Pancreas (2018). The Verona Evidence-Based Meeting 2020 was also presented and discussed.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, Katowice 40-752, Poland
| | - Paweł Szmigiel
- Department of Digestive Tract Surgery, Medical University of Silesia, Katowice 40-752, Poland
| | - Sławomir Mrowiec
- Department of Digestive Tract Surgery, Medical University of Silesia, Katowice 40-752, Poland
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20
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Stigliano S, Covotta F, Di Matteo FM. A new micro‐forceps for endoscopic ultrasound‐guided through‐the‐needle biopsy in the diagnosis of pancreatic cystic lesions: Single center experience. JGH Open 2021; 5:1004-1008. [PMID: 34584967 PMCID: PMC8454469 DOI: 10.1002/jgh3.12601] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 12/15/2022]
Affiliation(s)
- Serena Stigliano
- Operative Endoscopy Department Campus Bio‐Medico University Hospital Rome Italy
- Department of Translational and Precision Medicine Sapienza University Rome Italy
| | - Francesco Covotta
- Operative Endoscopy Department Campus Bio‐Medico University Hospital Rome Italy
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21
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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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22
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Guzmán-Calderón E, Martinez-Moreno B, Casellas JA, de Madaria E, Aparicio JR. Endoscopic ultrasound-guided, through-the-needle forceps biopsy for diagnosis of pancreatic cystic lesions: a systematic review. Endosc Int Open 2020; 8:E1123-E1133. [PMID: 32904862 PMCID: PMC7458739 DOI: 10.1055/a-1149-1647] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Pancreatic cystic lesions (PCL), are a heterogeneous group of cystic lesions. Some patients with PCLs have a significantly higher overall risk of pancreatic cancer and the only test that can differentiate benign and malignnat PCL is fine-needle aspiration plus cytological analysis, but its sensitivity is very low. Through-the-needle direct intracystic biopsy is a technique that allows acquisition of targeted tissue from PCLs and it may improve the diagnostic yield for them. The aim of this study was to review articles about endoscopic ultrasound (EUS)-guided through-the-needle intracystic biopsy for targeted tissue acquisition and diagnosis of PCLs. Methods A systematic review of computerized bibliographic databases was carried out for studies of EUS-guided through-the-needle forceps biopsy (EUS-TTNB) of PCLs. The percentages and their 95 % confidence intervals (CIs) were calculated for all the considered endpoints (technical success, adequate specimens, adverse events (AEs), and overall diagnosis). Results Overall, eight studies with a total of 423 patients were identified. Pooled technical success was 95.6 % of the cases (399/423), (95 % CI, 93.2 %-97.3 %). Technical failure rate was 5.1 % (24 cases). Frequency of adequate specimens was 82.2 %, (95 % CI, 78.5 %-85.8 %). Adverse events were reported in seven of the eight studies. Forty-two total adverse events were reported (10.1 %) (95 % CI, 7.3 %-13.6 %). The overall ability to provide a specific diagnosis with EUS-TTNB for diagnosis of pancreatic cystic lesions was 74.6 % (313 cases), (95 % CI: 70.2 %-78.7 %). The most frequent diagnoses found with EUS-TTNB were mucinous cystic neoplasms (MCN) in 96 cases (30.6 %), IPMN in 80 cases (25.5 %), and serous cystoadenoma neoplasm (SCN) in 48 cases (15.3 %). Conclusions Through-the-needle forceps biopsy appears to be effective and safe, with few AE for diagnosis of pancreatic cystic lesions. This technique had acceptable rates of technical and clinical success and an excellent safety profile. TTNB is associated with a high tissue acquisition yield and provided additional diagnostic yield for mucinous pancreatic lesions. TTNB may be a useful adjunctive tool for EUS-guided assessment of PCLs.
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Affiliation(s)
- Edson Guzmán-Calderón
- Gastroenterology Unit of Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru,Universidad Peruana de Ciencias Aplicadas (UPC), Alicante, Spain
| | | | - Juan A. Casellas
- Gastroenterology Unit oh Hospital General Universitario de Alicante, Alicante, Spain
| | - Enrique de Madaria
- 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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23
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Ohno E, Hirooka Y, Kawashima H, Ishikawa T, Fujishiro M. Endoscopic ultrasonography for the evaluation of pancreatic cystic neoplasms. J Med Ultrason (2001) 2020; 47:401-411. [PMID: 31605262 DOI: 10.1007/s10396-019-00980-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/11/2019] [Indexed: 12/12/2022]
Abstract
Endoscopic ultrasonography (EUS) is a modality with high spatial resolution that enables comprehensive observation of the entire pancreas and plays an important role in the diagnosis of pancreatic lesions. Recent advances in diagnostic imaging methods such as ultrasound, computed tomography, and magnetic resonance imaging have increased the incidental detection of pancreatic cystic lesions (PCLs). EUS has been recognized as an essential diagnostic method for the detection and evaluation of PCLs. EUS has two important roles: as a detailed (high-resolution) imaging diagnostic method and as an approach for collecting cyst fluid content by EUS-guided fine needle aspiration for pathological diagnosis or biomarker evaluation. Furthermore, in recent years, the usefulness of contrast-enhanced EUS for the differential diagnosis of PCLs or evaluation of grade of malignancy, and a novel imaging technique called needle-based confocal laser endomicroscopy to observe intraductal structures through a needle, has been reported. An understanding of the morphological characteristics of PCLs depicted by ultrasound imaging and of the benefits and limitations of EUS diagnosis in daily practice is needed.
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Affiliation(s)
- Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Yoshiki Hirooka
- Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, Aichi, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
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24
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Pan W, Chen M, Wu P, Chen C. Challenge in differentiation of pancreatic cystic neoplasms between intraductal papillary mucinous neoplasm and mucinous cystic neoplasm: A case report. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Wei‐Chin Pan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine MacKay Memorial Hospital Taipei Taiwan
| | - Ming‐Jen Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine MacKay Memorial Hospital Taipei Taiwan
- Department of Nursing MacKay Junior College of Medicine, Nursing, and Management Taipei Taiwan
- Department of Medicine MacKay Medical College New Taipei City Taiwan
| | - Pao‐Shu Wu
- Department of Medicine MacKay Medical College New Taipei City Taiwan
- Department of Pathology MacKay Memorial Hospital Taipei Taiwan
| | - Chih‐Jen Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine MacKay Memorial Hospital Taipei Taiwan
- Department of Nursing MacKay Junior College of Medicine, Nursing, and Management Taipei Taiwan
- Department of Medicine MacKay Medical College New Taipei City Taiwan
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Molecular Diagnosis of Cystic Neoplasms of the Pancreas: a Review. J Gastrointest Surg 2020; 24:1201-1214. [PMID: 32128679 DOI: 10.1007/s11605-020-04537-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 01/29/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prevalence of incidental pancreatic cystic neoplasms (PCNs) has increased dramatically with advancements in cross-sectional imaging. Diagnostic imaging is limited in differentiating between benign and malignant PCNs. The aim of this review is to provide an overview of biomarkers that can be used to distinguish PCNs. METHODS A review of the literature on molecular diagnosis of cystic neoplasms of the pancreas was performed. RESULTS Pancreatic cysts can be categorized into inflammatory and non-inflammatory lesions. Inflammatory cysts include pancreatic pseudocysts. Noninflammatory lesions include both mucinous and non-mucinous lesions. Mucinous lesions include intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm. Non-mucinous lesions include serous cystadenoma and solid-pseudopapillary tumor of the pancreas. Imaging, cyst aspiration, and histologic findings, as well as carcinoembryonic antigen and amylase are commonly used to distinguish between cyst types. However, molecular techniques to detect differences in genetic mutations, protein expression, glycoproteomics, and metabolomic profiling are important developments in distinguishing between cyst types. DISCUSSION Nomograms incorporating common clinical, laboratory, and imaging findings have been developed in a better effort to predict malignant IPMN. The incorporation of top molecular biomarker candidates to nomograms may improve the predictive ability of current models to more accurately diagnose malignant PCNs.
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Crippa S, Arcidiacono PG, De Cobelli F, Falconi M. Review of the diagnosis and management of intraductal papillary mucinous neoplasms. United European Gastroenterol J 2020; 8:249-255. [PMID: 32213017 PMCID: PMC7184662 DOI: 10.1177/2050640619894767] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 11/16/2019] [Indexed: 02/06/2023] Open
Abstract
Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.
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Affiliation(s)
- Stefano Crippa
- Division of Pancreatic Surgery, Vita e Salute University, Milan, Italy
| | - Paolo G Arcidiacono
- Division of Pancreato-Biliary Endoscopy and EUS, Vita e Salute University, Milan, Italy
| | | | - Massimo Falconi
- Division of Pancreatic Surgery, Vita e Salute University, Milan, Italy
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27
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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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Hashimoto R, Lee JG, Chang KJ, Chehade NEH, Samarasena JB. Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A large single center experience. World J Gastrointest Endosc 2019; 11:531-540. [PMID: 31798774 PMCID: PMC6875688 DOI: 10.4253/wjge.v11.i11.531] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 09/25/2019] [Accepted: 10/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Establishing a diagnosis of pancreatic cystic lesions (PCLs) preoperatively still remains challenging. Recently, endoscopic ultrasound (EUS)-through-the-needle biopsy (EUS-TTNB) using microforceps in PCLs has been made available. AIM To assess the efficacy and safety of EUS-TTNB in the diagnosis of PCLs. METHODS We retrospectively collected data of patients with PCLs who underwent both EUS-fine-needle aspiration (FNA) for cytology and EUS-TTNB at our institution since 2016. EUS-FNA for cytology was followed by EUS-TTNB in the same session. Evaluation of the cyst location, primary diagnosis, adverse events, and comparison between the cytologic fluid analyses and histopathology was performed. Technical success of EUS-TTNB was defined as visible tissue present after biopsy. Clinical success was defined as the presence of a specimen adequate to make a histologic or cytologic diagnosis. RESULTS A total of 56 patients (mean age 66.9 ± 11.7, 53.6% females) with PCLs were enrolled over the study period. The mean cyst size was 28.8 mm (12-85 mm). The EUS-TTNB procedure was technically successful in all patients (100%). The clinical success rate using EUS-TTNB was much higher than standard EUS-FNA, respectively 80.4% (45/56) vs 25% (14/56). Adverse events occurred in 2 patients (3.6%) who developed mild pancreatitis that resolved with medical therapy. Using TTNB specimens, 23 of 32 cases (71.9%) with intraductal papillary mucinous neoplasm were further differentiated into gastric type (19 patients) and pancreaticobiliary type (4 patients) based on immunochemical staining. CONCLUSION EUS-TTNB for PCLs was technically feasible and had a favorable safety profile. Furthermore, the diagnostic yield for PCLs was much higher with EUS-TTNB than standard EUS-FNA cytology and fluid carcinoembryonic antigen. EUS-TTNB should be considered as an adjunct to EUS-FNA and cytologic analysis in the diagnosis and management of PCLs.
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Affiliation(s)
- Rintaro Hashimoto
- H. H. Chao Comprehensive Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, Irvine, Orange, CA 92868, United States
| | - John G Lee
- H. H. Chao Comprehensive Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, Irvine, Orange, CA 92868, United States
| | - Kenneth J Chang
- H. H. Chao Comprehensive Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, Irvine, Orange, CA 92868, United States
| | - Nabil El Hage Chehade
- H. H. Chao Comprehensive Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, Irvine, Orange, CA 92868, United States
| | - Jason B Samarasena
- H. H. Chao Comprehensive Digestive Disease Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, Irvine, Orange, CA 92868, United States
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29
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Tanaka M, Heckler M, Liu B, Heger U, Hackert T, Michalski CW. Cytologic Analysis of Pancreatic Juice Increases Specificity of Detection of Malignant IPMN-A Systematic Review. Clin Gastroenterol Hepatol 2019; 17:2199-2211.e21. [PMID: 30630102 DOI: 10.1016/j.cgh.2018.12.034] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can progress to cancer. Biomarkers have been identified that were reported to increase the accuracy of identification of malignant lesions; we performed a systematic review of the accuracy of these markers. METHODS We performed a systematic review of published studies on biomarkers of malignant IPMNs by searching MEDLINE and Web of Science databases from January 2005 through December 2017. Our methods were developed based on the Meta-analysis Of Observational Studies in Epidemiology guidelines. Pooled sensitivity, specificity, receiver operating characteristic curves, and their respective areas under the curve (AUC) were calculated from groups of markers (cell-, protein-, or DNA-based) measured in samples collected before and after surgery. A hypothetical test model was developed to determine how to meaningfully amend the revised Fukuoka guidelines, focusing on increasing test specificity for patients with IPMNs that have worrisome features. RESULTS We collected data from 193 published studies, comprising 12,297 patients, that analyzed 7 preoperative and 21 postoperative markers of IPMNs. The 3 biomarkers that identified malignant IPMNs with the largest AUC values were pancreatic juice cytology (AUC, 0.84; sensitivity, 0.54; specificity, 0.91), serum protein carbohydrate antigen 19-9 (AUC, 0.81; sensitivity, 0.45; specificity, 0.90), and cyst fluid cytology (AUC, 0.82; sensitivity, 0.57; specificity, 0.84). A combination of cytologic and immunohistochemical analysis of MUC1 and MUC2 in pancreatic juice samples identified malignant IPMNs with the largest AUC and sensitivity values (AUC, 0.85; sensitivity, 0.85; specificity, 0.65). In a test model, inclusion of cytologic analysis of pancreatic juice in the guideline algorithm significantly increased the specificity of detection of malignant IPMNs. CONCLUSIONS In a systematic review, we found cytologic analysis of pancreatic juice to have the greatest effect in increasing the specificity of detection of malignant IPMNs. We propose addition of this test to the Fukuoka guidelines for assessment of patients with IPMNs with worrisome features.
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Affiliation(s)
- Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Bing Liu
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany.
| | - Christoph W Michalski
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany; Department of Surgery, Halle University Hospital, Martin Luther University Halle-Wittenberg, Halle, Germany
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30
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Laquière A, Lagarde A, Napoléon B, Bourdariat R, Atkinson A, Donatelli G, Pol B, Lecomte L, Curel L, Urena-Campos R, Helbert T, Valantin V, Mithieux F, Buono JP, Grandval P, Olschwang S. Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue. World J Gastroenterol 2019; 25:5530-5542. [PMID: 31576098 PMCID: PMC6767987 DOI: 10.3748/wjg.v25.i36.5530] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/16/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation.
AIM To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT.
METHODS Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated.
RESULTS Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively.
CONCLUSION Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.
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Affiliation(s)
- Arthur Laquière
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | - Arnaud Lagarde
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- AP-HM, Conception Hospital, Marseille 13385, France
| | | | | | | | | | - Bernard Pol
- Department of Digestive Surgery, Saint-Joseph Hospital, Marseille 13008, France
| | - Laurence Lecomte
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | - Laurence Curel
- Department of Clinical Research, Saint Joseph Hospital, Marseille 13008, France
| | - Romina Urena-Campos
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | | | | | | | | | - Philippe Grandval
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- AP-HM, Timone Hospital, Marseille 13005, France
| | - Sylviane Olschwang
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- European Hospital, Marseille 13003, France
- AP-HM, Timone Hospital, Marseille 13005, France
- RGDS, Clairval Hospital, Marseille 13009, France
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Pancreatic Cysts: Diagnostic Role of EUS-Guided Microforceps Biopsy and Confocal Laser Endomicroscopy. Gastroenterol Res Pract 2019; 2019:3431048. [PMID: 31611915 PMCID: PMC6757287 DOI: 10.1155/2019/3431048] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/22/2019] [Accepted: 08/06/2019] [Indexed: 02/08/2023] Open
Abstract
Frequent use of high-quality cross-sectional imaging has led to a significant rise in diagnosis of pancreatic cystic lesions (PCLs). Despite the fact that enormous effort has been put into the research of PCLs within the last two decades and multiple guidelines have been developed, our clinical decision-making especially in regard to mucinous lesions remains limited. Currently, clinical assessment, cross-sectional imaging and EUS with fluid analysis (if appropriate) belong to the standard care in patients with PCLs. For differentiation of mucinous from nonmucinous cysts, the sensitivity of cytological investigation and CEA in the cyst fluid is 42% and 52-79%, respectively. Due to the limited accuracy, further diagnostic tools are warranted. Two EUS-guided approaches have been introduced recently. Through-the-(19-gauge EUS) needle Moray microforceps have been developed, and several studies have acknowledged their contribution to the correct diagnosis as they help to overcome limited cellularity of the EUS-guided cyst fluid aspiration and traditional cytology. Confocal laser endomicroscopy offers real-time images and seems to be a promising method for the diagnosis and differential diagnosis of pancreatic PCLs. Example images of the needle-based confocal laser endomicroscopy criteria for the diagnosis of PCLs have been suggested recently. Before both, Moray microforceps and confocal laser endomicroscopy can be widely accepted, further studies are necessary to determine the real diagnostic yield and the clinical efficacy.
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Faias S, Pereira L, Luís Â, Chaves P, Cravo M. Genetic testing vs microforceps biopsy in pancreatic cysts: Systematic review and meta-analysis. World J Gastroenterol 2019; 25:3450-3467. [PMID: 31341368 PMCID: PMC6639554 DOI: 10.3748/wjg.v25.i26.3450] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/17/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.
AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.
METHODS We performed a literature search in Medline, Scopus, and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts, with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) prior to surgery and surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: 1- benign cysts; 2- mucinous low-risk cysts; 3- high-risk cysts, and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis. We also assessed publication bias, heterogeneity, and study quality.
RESULTS Eight studies, including 1206 patients, of which 203 (17%) referred for surgery who met the inclusion criteria were analyzed in the systematic review, and seven studies were included in the meta-analysis. Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts. Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts, with sensitivities of 0.89 (95%CI: 0.79-0.95) and 0.57 (95%CI: 0.42-0.71), specificities of 0.88 (95%CI: 0.75-0.95) and 0.88 (95%CI: 0.80-0.93) and AUC of 0.9555 and 0.92, respectively. The diagnostic yield was higher in microforceps biopsies than in genetic analysis (0.73 vs 0.54, respectively) but the rates of correctly identified cysts were identical (0.73 with 95%CI: 0.62-0.82 vs 0.71 with 95%CI: 0.49-0.86, respectively).
CONCLUSION Genetic testing and microforceps biopsies are useful second tests, with identical results in benign pancreatic cysts. Genetic analysis performs better for low- and high-risk cysts but has lower diagnostic yield.
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Affiliation(s)
- Sandra Faias
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Luisa Pereira
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Matemática e Aplicações (CMA-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Ângelo Luís
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Paula Chaves
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Department of Pathology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
| | - Marília Cravo
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa 1099-023, Portugal
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KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound-Fine-Needle Aspiration in Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis. Pancreas 2019; 48:749-758. [PMID: 31206466 DOI: 10.1097/mpa.0000000000001325] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53-0.65), specificity = 0.9 (95% CI, 0.76-0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27-0.48), specificity = 0.96 (95% CI, 0.93-0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34-0.43) and 0.46 (95% CI, 0.42-0.51), specificities = 0.62 (95% CI, 0.56-0.68) and 0.97 (95% CI, 0.92-0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.
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Şahin D, Çiçek B, Akpolat İ, Şişman G, Tekkeşin N. Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests? TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:903-909. [PMID: 31231069 DOI: 10.5152/tjg.2019.19006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.
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Affiliation(s)
- Davut Şahin
- Department of Pathology-Cytopathology, Acıbadem Health Group, İstanbul, Turkey
| | - Bahattin Çiçek
- Department of Gastroenterology, Acıbadem Mehmet Ali Aydınlar University, İstanbul, Turkey
| | - İlkser Akpolat
- Department of Pathology, Acıbadem Mehmet Ali Aydınlar University, İstanbul, Turkey
| | - Gürhan Şişman
- Department of Gastroenterology, Acıbadem Mehmet Ali Aydınlar University Atakent Hospital, İstanbul, Turkey
| | - Nilgün Tekkeşin
- Department of Biochemistry, Memorial Şişli Hospital, İstanbul, Turkey
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35
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Kamata K, Kitano M. Endoscopic diagnosis of cystic lesions of the pancreas. Dig Endosc 2019; 31:5-15. [PMID: 30085364 DOI: 10.1111/den.13257] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 08/02/2018] [Indexed: 12/13/2022]
Abstract
Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS-guided fine-needle aspiration cytology and EUS-guided fine needle-based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non-mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast-enhanced harmonic EUS (CH-EUS), as an add-on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH-EUS has a sensitivity of 60-100% and a specificity of 75-92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta-analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.
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Affiliation(s)
- Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Masayuki Kitano
- Second Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
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Abstract
The diagnostic approach to pancreaticobiliary disease requires a multidisciplinary team in which the cytopathologist plays a crucial role. Fine-needle aspiration, obtained by endoscopic ultrasound, is the diagnostic test of choice for pancreatic lesions. Preoperative clinical management depends on many factors, many of which rely on accurate cytologic assessment. Pancreaticobiliary cytology is wrought with diagnostic pitfalls. Clinical history, imaging studies, cytology samples, and ancillary tests, including immunohistochemistry, biochemical analysis, and genetic sequencing, are integral to forming a complete diagnosis and guiding optimal patient management. This article reviews clinical aspects and the diagnostic work-up of commonly encountered diagnostic entities within the field of pancreatic cytology.
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Affiliation(s)
- Raza S Hoda
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
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Faias S, Duarte M, Albuquerque C, da Silva JP, Fonseca R, Roque R, Dias Pereira A, Chaves P, Cravo M. Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA. Dig Dis Sci 2018; 63:2351-2361. [PMID: 29796909 DOI: 10.1007/s10620-018-5128-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 05/17/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/blood
- Biomarkers, Tumor/genetics
- Carcinoembryonic Antigen/blood
- Carcinoma/blood
- Carcinoma/genetics
- Carcinoma/pathology
- Carcinoma/therapy
- Chromogranins/genetics
- DNA Mutational Analysis
- Endoscopic Ultrasound-Guided Fine Needle Aspiration
- Exons
- Female
- GTP-Binding Protein alpha Subunits, Gs/genetics
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Mutation
- Neoplasms, Cystic, Mucinous, and Serous/blood
- Neoplasms, Cystic, Mucinous, and Serous/genetics
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/therapy
- Pancreatic Cyst/blood
- Pancreatic Cyst/genetics
- Pancreatic Cyst/pathology
- Pancreatic Cyst/therapy
- Pancreatic Neoplasms/blood
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/therapy
- Phenotype
- Predictive Value of Tests
- Proto-Oncogene Proteins p21(ras)/genetics
- Retrospective Studies
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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.
| | - Marlene Duarte
- Molecular Pathobiology Investigation Center, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - Cristina Albuquerque
- Molecular Pathobiology Investigation Center, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, 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
| | - Ricardo Fonseca
- Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
| | - Ruben Roque
- Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal
| | - Antonio Dias Pereira
- 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
| | - Marília Cravo
- Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal
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The European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018; 67:789-804. [PMID: 29574408 PMCID: PMC5890653 DOI: 10.1136/gutjnl-2018-316027] [Citation(s) in RCA: 870] [Impact Index Per Article: 124.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 02/13/2018] [Accepted: 02/13/2018] [Indexed: 02/07/2023]
Abstract
Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic Cancer. Cancers (Basel) 2018; 10:cancers10020035. [PMID: 29382047 PMCID: PMC5836067 DOI: 10.3390/cancers10020035] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 01/24/2018] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Advanced pancreatic cancer (PC) is an aggressive malignancy with few effective therapeutic options. While the evolution of precision medicine in recent decades has changed the treatment landscape in many cancers, at present no targeted therapies are used in the routine management of PC. Only a minority of patients with PC present with surgically resectable disease, and in the remainder obtaining high quality biopsy material for both diagnosis and molecular testing can prove challenging. Endoscopic ultrasound-guided fine needle aspiration (EUS FNA) is a widely used diagnostic procedure in PC, and allows tumour sampling in patients with both early and late stage disease. This review will provide an update on the role of EUS FNA as a diagnostic tool, as well as a source of genetic material which can be used both for molecular analysis and for the creation of valuable preclinical disease models. We will also consider relevant clinical applications of EUS FNA in the management of PC, and the path towards bringing precision medicine closer to the clinic in this challenging disease.
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40
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Aronsson L, Andersson R, Swahn F, Ansari D. Does next-generation sequencing of cyst fluid improve management of pancreatic cystic neoplasms? Scand J Gastroenterol 2017; 52:1049-1051. [PMID: 28678564 DOI: 10.1080/00365521.2017.1349175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Pancreatic cystic lesions represent a heterogeneous group of diseases ranging from benign to malignant lesions. They are increasingly being detected due to the widespread use of cross-sectional imaging. Their management is a challenge because it is often not possible to reliably discriminate between malignant and nonmalignant lesions using current imaging technology. Next-generation sequencing (NGS) has the ability of both whole genome and targeted sequencing at a low cost and from a limited amount of DNA. NGS of cyst fluid aspired by endoscopic ultrasonography-guided fine-needle aspiration provides a valuable tool in biomarker research and may in the future help improve diagnosis and management of pancreatic cystic lesions.
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MESH Headings
- Cyst Fluid/chemistry
- High-Throughput Nucleotide Sequencing
- Humans
- Neoplasms, Cystic, Mucinous, and Serous/diagnosis
- Neoplasms, Cystic, Mucinous, and Serous/genetics
- Neoplasms, Cystic, Mucinous, and Serous/therapy
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/therapy
- Sequence Analysis, DNA
- Sequence Analysis, RNA
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Affiliation(s)
- Linus Aronsson
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Roland Andersson
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Fredrik Swahn
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
| | - Daniel Ansari
- a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden Surgery
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Du C, Chai NL, Linghu EQ, Li HK, Sun YF, Xu W, Wang XD, Tang P, Yang J. Incidents and adverse events of endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions. World J Gastroenterol 2017; 23:5610-5618. [PMID: 28852320 PMCID: PMC5558124 DOI: 10.3748/wjg.v23.i30.5610] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 06/12/2017] [Accepted: 06/18/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the diagnostic value and safety mainly regarding incidents of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cystic lesions (PCLs). METHODS A total of 150 consecutive patients with suspected PCLs were prospectively enrolled from April 2015 to November 2016. We finally enrolled 140 patients undergoing EUS-FNA. We compared the diagnostic accuracy of EUS-FNA and pathological diagnosis, which is regarded as the gold standard, for PCLs. Patients undergoing EUS-FNA at least 1 wk preoperatively were monitored for incidents and adverse events to evaluate its safety. RESULTS There were 88 (62.9%) women and 52 (37.1%) men among 140 patients, with a mean age of 50.1 (± 15.4) years. There were 67 cysts located in the head/uncinate of the pancreas and 67 in the body/tail, and 6 patients had at least 1 cyst in the pancreas. There were 75 patients undergoing surgery and 55 undergoing EUS-FNA with interval at least 1 wk before other operations, with 3 patients undergoing the procedure twice. The accuracy of EUS-FNA in differentiating benign and malignant lesions was 97.3% (73/75), while the accuracy of characterizing PCL subtype was 84.0% (63/75). The incident rate was 37.9% (22/58), whereas only 1 AE was observed in 58 cases. CONCLUSION EUS-FNA is effective and safe for diagnosis of PCLs, however procedure-related incidents are common. Caution should be taken in patients undergoing EUS-FNA.
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Abstract
Pancreatic cysts are commonly found on cross-sectional imaging. The question arises in determining which lesions are premalignant or malignant and may require further testing, intervention, or follow-up. In pancreatic cysts without obvious malignancy on imaging, we approach them using the Four "S" Criteria. These are (1) symptoms that may be originating from the pancreatic cyst; (2) size of the cyst 2 cm or larger and/or main pancreatic duct greater than 5 mm; (3) survival of the patient, based on comorbidity index to determine surgical fitness; and then endoscopic ultrasound with fine needle aspiration (FNA) recommended to determine (4) solid component presence in the cyst, namely, nodule or thick walls, as well as to perform FNA to obtain cyst content. Current cyst fluid analysis options include use of cytology to determine presence of malignancy and carcinoembryonic antigen and fluid genetics to identify potentially premalignant lesions. The aims of this article are to explore current management guidelines for pancreatic cysts, present a comprehensive approach to pancreatic cysts, and explain the advantages and disadvantages of each option for evaluation of pancreatic cysts including endoscopic ultrasound with FNA with cyst fluid analysis using an evidence-based approach.
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43
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Megibow AJ, Baker ME, Morgan DE, Kamel IR, Sahani DV, Newman E, Brugge WR, Berland LL, Pandharipande PV. Management of Incidental Pancreatic Cysts: A White Paper of the ACR Incidental Findings Committee. J Am Coll Radiol 2017; 14:911-923. [PMID: 28533111 DOI: 10.1016/j.jacr.2017.03.010] [Citation(s) in RCA: 209] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 02/27/2017] [Accepted: 03/13/2017] [Indexed: 12/12/2022]
Abstract
The ACR Incidental Findings Committee (IFC) presents recommendations for managing pancreatic cysts that are incidentally detected on CT or MRI. These recommendations represent an update from the pancreatic component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Pancreas Subcommittee-which included abdominal radiologists, a gastroenterologist, and a pancreatic surgeon-developed this algorithm. The recommendations draw from published evidence and expert opinion, and were finalized by informal iterative consensus. Algorithm branches successively categorize pancreatic cysts based on patient characteristics and imaging features. They terminate with an ascertainment of benignity and/or indolence (sufficient to discontinue follow-up), or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. Our goal is to improve quality of care by providing guidance on how to manage incidentally detected pancreatic cysts.
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Affiliation(s)
- Alec J Megibow
- Department of Radiology, NYU-Langone Medical Center, New York, New York.
| | - Mark E Baker
- Department of Radiology, Cleveland Clinic, Cleveland, Ohio
| | - Desiree E Morgan
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Ihab R Kamel
- Department of Radiology, Johns Hopkins Hospital, Baltimore, Maryland
| | - Dushyant V Sahani
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts
| | - Elliot Newman
- Department of Surgery, NYU-Langone Medical Center, New York, New York
| | - William R Brugge
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Lincoln L Berland
- Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Pari V Pandharipande
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts; Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts
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Best LMJ, Rawji V, Pereira SP, Davidson BR, Gurusamy KS, Cochrane Upper GI and Pancreatic Diseases Group. Imaging modalities for characterising focal pancreatic lesions. Cochrane Database Syst Rev 2017; 4:CD010213. [PMID: 28415140 PMCID: PMC6478242 DOI: 10.1002/14651858.cd010213.pub2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. OBJECTIVES To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. SEARCH METHODS We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. DATA COLLECTION AND ANALYSIS Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. MAIN RESULTS We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. AUTHORS' CONCLUSIONS We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.
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Affiliation(s)
- Lawrence MJ Best
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRowland Hill StreetLondonUKNW32PF
| | - Vishal Rawji
- University College London Medical SchoolLondonUK
| | - Stephen P Pereira
- Royal Free Hospital CampusUCL Institute for Liver and Digestive HealthUpper 3rd FloorLondonUKNW3 2PF
| | - Brian R Davidson
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRowland Hill StreetLondonUKNW32PF
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Kameta E, Sugimori K, Kaneko T, Ishii T, Miwa H, Sato T, Ishii Y, Sue S, Sasaki T, Yamashita Y, Shibata W, Matsumoto N, Maeda S. Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing. Oncol Lett 2016; 12:3875-3881. [PMID: 27895743 PMCID: PMC5104195 DOI: 10.3892/ol.2016.5168] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2015] [Accepted: 08/10/2016] [Indexed: 12/25/2022] Open
Abstract
Endoscopic ultrasound-guided fine-needle aspiration (EUF-FNA) has improved the diagnosis of pancreatic lesions. Next-generation sequencing (NGS) facilitates the production of millions of sequences concurrently. Therefore, in the current study, to improve the detectability of oncogenic mutations in pancreatic lesions, an NGS system was used to diagnose EUS-FNA samples. A total of 38 patients with clinically diagnosed EUS-FNA specimens were analyzed; 27 patients had pancreatic ductal adenocarcinoma (PDAC) and 11 had non-PDAC lesions. DNA samples were isolated and sequenced by NGS using an Ion Personal Genome Machine system. The Cancer Hotspot Panel v2, which includes 50 cancer-related genes and 2,790 COSMIC mutations, was used. A >2% mutation frequency was defined as positive. KRAS mutations were detected in 26 of 27 PDAC aspirates (96%) and 0 of 11 non-PDAC lesions (0%). The G12, G13, and Q61 KRAS mutations were found in 25, 0, and 1 of the 27 PDAC samples, respectively. Mutations were confirmed by TaqMan® polymerase chain reaction analysis. TP53 mutations were detected in 12 of 27 PDAC aspirates (44%). SMAD4 was observed in 3 PDAC lesions and cyclin-dependent kinase inhibitor 2A in 4 PDAC lesions. Therefore, the current study was successfully able to develop an NGS assay with high clinical sensitivity for EUS-FNA samples.
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Affiliation(s)
- Eri Kameta
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Kazuya Sugimori
- Gastroenterological Centre, Yokohama City University Medical Centre, Yokohama 232-0024, Japan
| | - Takashi Kaneko
- Gastroenterological Centre, Yokohama City University Medical Centre, Yokohama 232-0024, Japan
| | - Tomohiro Ishii
- Gastroenterological Centre, Yokohama City University Medical Centre, Yokohama 232-0024, Japan
| | - Haruo Miwa
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Takeshi Sato
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Yasuaki Ishii
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Tomohiko Sasaki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Yuki Yamashita
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Wataru Shibata
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
- Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
| | - Naomichi Matsumoto
- Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
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Gleeson FC, Levy MJ. The evolving field of genomic biomarkers to characterize pancreatic cystic neoplasia by EUS-guided FNA. Gastrointest Endosc 2016; 83:149-50. [PMID: 26227930 DOI: 10.1016/j.gie.2015.07.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 07/17/2015] [Indexed: 02/08/2023]
Affiliation(s)
- Ferga C Gleeson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael J Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Abstract
Cystic lesions of the pancreas (CLPs) are increasingly diagnosed due to the growing utilization of cross-sectional imaging modalities. The differentiation between true cysts (epithelial tumors) and nonepithelial lesions (such as pseudocysts) relies on clinical and imaging characteristics, but more reliably obtained by endoscopic ultrasound (EUS) fine-needle aspiration. Due to their malignant potential, some of the true pancreatic cysts require further assessment and periodic follow-up. Therefore, it is important to establish a solid diagnosis at the time of detection of the various types of pancreatic cysts. Due to the limitations of cytology and biochemical markers in accurately classifying cyst pathology, the search for specific molecular markers associated with each type of cyst is ongoing. In this chapter, we will review some of the emerging molecular markers in pancreatic cystic fluid and their potential impact on endosonography and pancreatic cyst management.
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Affiliation(s)
- Mohammad Al-Haddad
- Department of Gastroenterology, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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48
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Smith AL, Abdul-Karim FW, Goyal A. Cytologic categorization of pancreatic neoplastic mucinous cysts with an assessment of the risk of malignancy: A retrospective study based on the Papanicolaou Society of Cytopathology guidelines. Cancer Cytopathol 2015; 124:285-93. [DOI: 10.1002/cncy.21657] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 10/27/2015] [Accepted: 10/28/2015] [Indexed: 12/13/2022]
Affiliation(s)
- Amber L. Smith
- Department of Pathology; Cleveland Clinic; Cleveland Ohio
| | | | - Abha Goyal
- Department of Pathology; Cleveland Clinic; Cleveland Ohio
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Martin AK, Zhou Z. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic cysts by combined cytopathology and cystic content analysis. World J Gastrointest Endosc 2015; 7:1157-1169. [PMID: 26504505 PMCID: PMC4613805 DOI: 10.4253/wjge.v7.i15.1157] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/03/2015] [Accepted: 09/08/2015] [Indexed: 02/05/2023] Open
Abstract
Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUS-guided FNA and the cytological diagnosis for pancreatic cysts.
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50
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Abstract
BACKGROUND Pancreatic cystic lesions (PCL) are common. They are increasingly detected as an incidental finding of transabdominal ultrasound or cross-sectional imaging. In contrast to other parenchymal organs, dysontogenetic pancreatic cysts are extremely rare. In symptomatic patients the most frequent PCL are acute and chronic pseudocysts. The majority of incidental cystic lesions, however, are neoplasias which have different risks of malignancy. METHODS PubMed was searched for studies, reviews, meta-analyses, and guidelines using the following key words: ('pancreatic cystic lesions' OR 'cystic pancreatic lesions' OR 'intraductal papillary mucinous neoplasia' OR 'mucinous cystic neoplasia' OR 'pancreatic cyst' OR 'pancreatic pseudocyst') AND (management OR treatment OR outcome OR prognosis OR diagnosis OR imaging OR 'endoscopic ultrasound' EUS-FNA OR EUS OR 'endoscopic ultrasonography' OR CT OR MRI). Retrieved papers were reviewed with regard to the diagnostic and therapeutic management of incidental PCL. RESULTS In addition to clinical criteria, transabdominal ultrasonography including contrast-enhanced ultrasonography, cross-sectional radiological imaging, and endoscopic ultrasound (EUS) are used for diagnostic characterization and risk assessment. EUS plays an outstanding role in differential diagnosis and prognostic characterization of incidental PCL. In a single examination it is possible to perform high-resolution morphological description, perfusion imaging, as well as fine-needle aspiration of cyst content, cyst wall, and solid components. An international consensus guideline has defined worrisome and high-risk criteria for the risk assessment of mucinous pancreatic cysts, which are mainly based on the results of EUS and cross-sectional imaging. Nevertheless, despite diagnostic progress and guideline recommendations, differential diagnosis and management decisions remain difficult. This review will discuss problems in and approaches to the diagnosis of incidental PCL. CONCLUSION An evidence-based algorithm for the diagnosis of incidental PCL is proposed.
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Affiliation(s)
- Christian Jenssen
- Department of Internal Medicine, Märkisch Oderland Hospital GmbH, Strausberg/Wriezen, Germany
| | - Stefan Kahl
- Department of Internal Medicine, DRK Kliniken Berlin - Köpenick, Berlin, Germany
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