|
1
|
Thierens NDE, Verdonk RC, Löhr JM, van Santvoort HC, Bouwense SA, van Hooft JE. Chronic pancreatitis. Lancet 2025; 404:2605-2618. [PMID: 39647500 DOI: 10.1016/s0140-6736(24)02187-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 09/20/2024] [Accepted: 10/01/2024] [Indexed: 12/10/2024]
Abstract
Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.
Collapse
Affiliation(s)
- Naomi DE Thierens
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Research and Development, St Antonius Hospital, Nieuwegein, Netherlands.
| | - Robert C Verdonk
- Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands
| | - J Matthias Löhr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Hjalmar C van Santvoort
- Department of Surgery, St Antonius Hospital, Nieuwegein, Netherlands; Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands
| | - Stefan Aw Bouwense
- Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands
| |
Collapse
|
|
2
|
Heller M, Mann DA, Katona BW. Current Approaches of Pancreatic Cancer Surveillance in High-Risk Individuals. J Gastrointest Cancer 2025; 56:61. [PMID: 39932614 PMCID: PMC11814005 DOI: 10.1007/s12029-025-01184-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2025] [Indexed: 02/14/2025]
Abstract
Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for PC and increased use of PC surveillance in clinical practice, there has been increasing debate about who should undergo surveillance as well as how surveillance should be performed including use of imaging and blood-based testing. Furthermore, there is increasing interest in the outcomes of PC surveillance in high-risk individuals with some studies demonstrating that surveillance leads to downstaging of PC and improvements in survival. In this review, we summarize the current state of PC surveillance in high-risk individuals, providing an overview of the risk factors associated with PC, selection of high-risk individuals for PC surveillance, and the current, but non-uniform, recommendations for performing PC surveillance. Additionally, we review approaches to apply various imaging and blood-based tests to surveillance and the outcomes of PC surveillance.
Collapse
Affiliation(s)
- Melissa Heller
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Derek A Mann
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd., 751 South Pavilion, Philadelphia, PA, 19104, USA.
| |
Collapse
|
|
3
|
Milano RV, Morneault-Gill K, Kamal HY, Barkin JA, Chadwick CB. Pancreatitis in cystic fibrosis: Presentation, medical and surgical management, and the impact of modulator therapies. Pediatr Pulmonol 2024; 59 Suppl 1:S53-S60. [PMID: 38501345 DOI: 10.1002/ppul.26958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 01/19/2024] [Accepted: 03/01/2024] [Indexed: 03/20/2024]
Abstract
Patients with Cystic Fibrosis (CF) are at increased risk of acute (AP) and chronic (CP) pancreatitis, and their complications. The extent of remaining healthy pancreatic parenchyma determines the risk of developing future episodes of pancreatitis, as well as pancreatic exocrine or endocrine insufficiency. Pancreatitis may be the presenting symptom of CF, and genetic testing is especially important in pediatrics. AP and recurrent AP are managed with intravenous fluid hydration and pain control, in addition to early refeeding and treatment of complications. With the use of modulator therapy in CF, pancreatic function may be restored to some extent. CP related pain is managed with analgesics and neuromodulators, with surgery if indicated in specific situations including TPIAT as a possible type of surgical intervention. Long-term sequelae of CP in patients with CF include exocrine pancreatic insufficiency treated with pancreatic enzyme replacement therapy, fat-soluble vitamin deficiencies and associated metabolic complications such as bone disease/osteoporosis, pancreatogenic diabetes, and less commonly, pancreatic cancer. We review the presentation and etiologies of pancreatitis in CF patients as well as the management of AP and CP primarily in children.
Collapse
Affiliation(s)
- Reza V Milano
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA
| | - Kayla Morneault-Gill
- Department of Pediatrics, Division of Gastroenterology, University of Florida, College of Medicine, Gainesville, Florida, USA
| | - Hebat Y Kamal
- Department of Pediatrics, Division of Gastroenterology, University of Florida, College of Medicine, Gainesville, Florida, USA
| | - Jodie A Barkin
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA
| | - Christina Baldwin Chadwick
- Department of Pediatrics, Division of Gastroenterology, University of Florida, College of Medicine, Gainesville, Florida, USA
| |
Collapse
|
|
4
|
Jacobs MF, Stoffel EM. Genetic and other risk factors for pancreatic ductal adenocarcinoma (PDAC). Fam Cancer 2024; 23:221-232. [PMID: 38573398 DOI: 10.1007/s10689-024-00372-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/07/2024] [Indexed: 04/05/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in poor prognosis and low 5-year survival rates. While early evidence suggests increased long-term survival in those with screen-detected resectable cancers, surveillance imaging is currently only recommended for individuals with a lifetime risk of PDAC ≥ 5%. Identification of risk factors for PDAC provides opportunities for early detection, risk reducing interventions, and targeted therapies, thus potentially improving patient outcomes. Here, we summarize modifiable and non-modifiable risk factors for PDAC. We review hereditary cancer syndromes associated with risk for PDAC and their implications for patients and their relatives. In addition, other biologically relevant pathways and environmental and lifestyle risk factors are discussed. Future work may focus on elucidating additional genetic, environmental, and lifestyle risk factors that may modify PDAC risk to continue to identify individuals at increased risk for PDAC who may benefit from surveillance and risk reducing interventions.
Collapse
Affiliation(s)
- Michelle F Jacobs
- Division of Genetic Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Elena M Stoffel
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
| |
Collapse
|
|
5
|
Angyal D, Kleinfelder K, Ciciriello F, Groeneweg TA, De Marchi G, de Pretis N, Bernardoni L, Rodella L, Tomba F, De Angelis P, Surace C, Pintani E, Alghisi F, de Jonge HR, Melotti P, Sorio C, Lucidi V, Bijvelds MJC, Frulloni L. CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants. Pancreatology 2024; 24:394-403. [PMID: 38493004 DOI: 10.1016/j.pan.2024.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 03/07/2024] [Accepted: 03/08/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). RESULTS Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. CONCLUSIONS CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.
Collapse
Affiliation(s)
- Dora Angyal
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, the Netherlands
| | - Karina Kleinfelder
- Department of Medicine, University of Verona, Division of General Pathology, Verona, Italy
| | - Fabiana Ciciriello
- Cystic Fibrosis Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio 4, 00165, Rome, Italy
| | - Tessa A Groeneweg
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, the Netherlands
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, Borgo Roma Hospital, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Nicolò de Pretis
- Gastroenterology Unit, Department of Medicine, Borgo Roma Hospital, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology Unit, Department of Medicine, Borgo Roma Hospital, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Luca Rodella
- Endoscopy Surgery Unit, Azienda Ospedaliera Universitaria Integrata Verona, 37126, Verona, Italy
| | - Francesco Tomba
- Endoscopy Surgery Unit, Azienda Ospedaliera Universitaria Integrata Verona, 37126, Verona, Italy
| | - Paola De Angelis
- Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Cecilia Surace
- Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, 00146, Rome, Italy
| | - Emily Pintani
- Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Federico Alghisi
- Cystic Fibrosis Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio 4, 00165, Rome, Italy
| | - Hugo R de Jonge
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, the Netherlands
| | - Paola Melotti
- Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Claudio Sorio
- Department of Medicine, University of Verona, Division of General Pathology, Verona, Italy
| | - Vincenzina Lucidi
- Cystic Fibrosis Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio 4, 00165, Rome, Italy
| | - Marcel J C Bijvelds
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, P.O. Box 2040, 3000, CA, Rotterdam, the Netherlands.
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Borgo Roma Hospital, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| |
Collapse
|
|
6
|
Lanzillotta M, Belli LI, Belfiori G, Palumbo D, Schiavo-Lena M, Capurso G, Arcidiacono PG, Dagna L, Falconi M, Crippa S, Della-Torre E. Association of autoimmune pancreatitis and intraductal papillary mucinous neoplasm. A retrospective analysis from a tertiary care referral center. Pancreatology 2024; 24:456-462. [PMID: 38448348 DOI: 10.1016/j.pan.2024.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 02/05/2024] [Accepted: 02/24/2024] [Indexed: 03/08/2024]
Abstract
BACKGROUND Autoimmune Pancreatitis (AIP) is a rare chronic inflammatory disease affecting the pancreas. Chronic pancreatic inflammation represents a risk factor for pre-neoplastic conditions such as Intraductal Papillary Mucinous Neoplasia (IPMN). Due to the rarity of AIP, the incidence, and clinical features of IPMN occurring in AIP patients remains unknown. AIMS In the present study we aimed to explore the relationship between AIP and IPMN and to characterize the clinical features and outcomes of IPMN occurring in the context of AIP. METHODS We retrospectively (2008-2020) analyzed the clinical and radiological records of a large single center cohort of patients with AIP and investigated the prevalence of IPMN. We then compared the clinical, laboratory and radiological characteristics of patients with IPMN and AIP with a cohort of patients with isolated IPMN. RESULTS Five hundred and nineteen patients were included in this retrospective study. Sixteen patients had concomitant IPMN and AIP(3%); 61 patients had isolated AIP (12%); 442 patients had isolated IPMN (85%). The prevalence of IPMN in patients with AIP was higher than that observed in the general population (21%vs8-10%). Worrisome Features and High-Risk Stigmata were more frequently observed in IPMN occurring together with AIP compared to isolated IPMN(p < 0.05). Based on radiological features IPMN in the context of AIP was more frequently of main-duct type compared to isolated IPMN(p < 0.05). CONCLUSION Our data suggest that AIP represents a chronic inflammatory condition that might favor IPMN development with high-risk features. Prolonged surveillance of these patients and longitudinal studies are required to further test the association with AIP and malignant and pre-malignant conditions.
Collapse
Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Lino Iago Belli
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giulio Belfiori
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Diego Palumbo
- Department of Radiology, IRCCS, San Raffaele Scientific Institute, Milan, Italy
| | - Marco Schiavo-Lena
- Unit of Pathology, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Lorenzo Dagna
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Crippa
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| |
Collapse
|
|
7
|
Sirtl S, Vornhülz M, Hofmann FO, Mayerle J, Beyer G. [Pancreatic cancer-screening or surveillance?]. RADIOLOGIE (HEIDELBERG, GERMANY) 2023; 63:908-915. [PMID: 37878016 DOI: 10.1007/s00117-023-01227-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Abstract
BACKGROUND Despite continuous improvement of diagnostic and therapeutic procedures, the number of new pancreatic ductal adenocarcinoma (PDAC) cases diagnosed annually almost equals the number of PDAC-related deaths. Prerequisite for curative treatment is a resectable tumor at the time of diagnosis. Individuals with genetic and/or familial risk profiles should therefore be screened and included in structured surveillance programs. OBJECTIVES Description of the status quo and usefulness of current PDAC screening and surveillance concepts. METHODS A selective literature search of current national and international guidelines including underlying literature was performed. RESULTS Nearly half of pancreatic cancer cases are missed by currently available surveillance programs, even in high-risk cohorts. Magnetic resonance imaging and endoscopic ultrasound supplemented by CA19‑9 (± HbA1c) are not accurate enough to ensure robust earlier pancreatic cancer detection. Complementary biomarker panels will take on a crucial diagnostic role in the future.
Collapse
Affiliation(s)
- Simon Sirtl
- Medizinische Klinik und Poliklinik II, LMU Klinikum, 81377, München, Deutschland.
| | - Marlies Vornhülz
- Medizinische Klinik und Poliklinik II, LMU Klinikum, 81377, München, Deutschland
| | - Felix O Hofmann
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, LMU Klinikum, München, Deutschland
| | - Julia Mayerle
- Medizinische Klinik und Poliklinik II, LMU Klinikum, 81377, München, Deutschland.
| | - Georg Beyer
- Medizinische Klinik und Poliklinik II, LMU Klinikum, 81377, München, Deutschland
| |
Collapse
|
|
8
|
Mahapatra SJ, Garg PK. The Power of Population Cohorts and Modeling: Pancreatitis-A Case in Point. Gastroenterology 2023; 165:1329-1333. [PMID: 37806459 DOI: 10.1053/j.gastro.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 10/01/2023] [Indexed: 10/10/2023]
Affiliation(s)
| | - Pramod Kumar Garg
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
| |
Collapse
|
|
9
|
Stoffel EM, Brand RE, Goggins M. Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention. Gastroenterology 2023; 164:752-765. [PMID: 36804602 DOI: 10.1053/j.gastro.2023.02.012] [Citation(s) in RCA: 172] [Impact Index Per Article: 86.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/10/2023] [Accepted: 02/11/2023] [Indexed: 02/23/2023]
Abstract
Pancreatic cancer usually results in poor survival with limited options for treatment, as most affected individuals present with advanced disease. Early detection of preinvasive pancreatic neoplasia and identifying molecular therapeutic targets provide opportunities for extending survival. Although screening for pancreatic cancer is currently not recommended for the general population, emerging evidence indicates that pancreatic surveillance can improve outcomes for individuals in certain high-risk groups. Changes in the epidemiology of pancreatic cancer, experience from pancreatic surveillance, and discovery of novel biomarkers provide a roadmap for new strategies for pancreatic cancer risk assessment, early detection, and prevention.
Collapse
Affiliation(s)
- Elena M Stoffel
- Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan.
| | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Michael Goggins
- Departments of Medicine and Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
10
|
Mazer BL, Lee JW, Roberts NJ, Chu LC, Lennon AM, Klein AP, Eshleman JR, Fishman EK, Canto MI, Goggins MG, Hruban RH. Screening for pancreatic cancer has the potential to save lives, but is it practical? Expert Rev Gastroenterol Hepatol 2023; 17:555-574. [PMID: 37212770 PMCID: PMC10424088 DOI: 10.1080/17474124.2023.2217354] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/21/2023] [Accepted: 05/19/2023] [Indexed: 05/23/2023]
Abstract
INTRODUCTION Most patients with pancreatic cancer present with advanced stage, incurable disease. However, patients with high-grade precancerous lesions and many patients with low-stage disease can be cured with surgery, suggesting that early detection has the potential to improve survival. While serum CA19.9 has been a long-standing biomarker used for pancreatic cancer disease monitoring, its low sensitivity and poor specificity have driven investigators to hunt for better diagnostic markers. AREAS COVERED This review will cover recent advances in genetics, proteomics, imaging, and artificial intelligence, which offer opportunities for the early detection of curable pancreatic neoplasms. EXPERT OPINION From exosomes, to circulating tumor DNA, to subtle changes on imaging, we know much more now about the biology and clinical manifestations of early pancreatic neoplasia than we did just five years ago. The overriding challenge, however, remains the development of a practical approach to screen for a relatively rare, but deadly, disease that is often treated with complex surgery. It is our hope that future advances will bring us closer to an effective and financially sound approach for the early detection of pancreatic cancer and its precursors.
Collapse
Affiliation(s)
- Benjamin L. Mazer
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jae W. Lee
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
| | - Nicholas J. Roberts
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Linda C. Chu
- Department of Radiology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anne Marie Lennon
- Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alison P. Klein
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James R. Eshleman
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K. Fishman
- Department of Radiology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Marcia Irene Canto
- Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Michael G. Goggins
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ralph H. Hruban
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
11
|
Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022. [DOI: https://doi.org/10.5306/wjco.v13.i11.907] [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: 12/03/2022] Open
|
|
12
|
Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World J Clin Oncol 2022; 13:907-917. [PMID: 36483975 PMCID: PMC9724185 DOI: 10.5306/wjco.v13.i11.907] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/08/2022] [Accepted: 11/07/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Epidemiological studies of chronic pancreatitis (CP) and its association with pancreatic ductal adenocarcinoma (PDAC) are limited. Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.
AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC. The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.
METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases. Patients included in the study had ICD-10 codes for CP and PDAC. The ethnic, socioeconomic, and racial backgrounds of patients with CP and PDAC were analyzed.
RESULTS Hospital admissions for CP was 29 per 100000, and 2890 (0.78%) had PDAC. Blacks [adjusted odds ratio (aOR) 1.13], men (aOR 1.35), age 40 to 59 (aOR 2.60), and being overweight (aOR 1.34) were significantly associated with CP (all with P < 0.01). In patients with CP, Whites (aOR 1.23), higher income, older age (aOR 1.05), and being overweight (aOR 2.40) were all significantly associated with PDAC (all with P < 0.01). Men (aOR 1.81) and Asians (aOR 15.19) had significantly increased mortality (P < 0.05). Hispanics had significantly increased hospital length of stay (aOR 5.24) (P < 0.05).
CONCLUSION Based on this large, nationwide analysis, black men between 40-59 years old and overweight are at significantly increased risk for admission with CP. White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC. This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.
Collapse
Affiliation(s)
- Daniel Lew
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Fatima Kamal
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Khiem Phan
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Karamvir Randhawa
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Sam Cornwell
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Ayrton I Bangolo
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Simcha Weissman
- Department of Internal Medicine, Hackensack Meridian Health/Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Stephen J Pandol
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| |
Collapse
|
|
13
|
Kawamoto M, Yoshida T, Tamura K, Dbouk M, Canto MI, Burkhart R, He J, Roberts NJ, Klein AP, Goggins M. Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk. Pancreatology 2022; 22:959-964. [PMID: 35995657 PMCID: PMC9669157 DOI: 10.1016/j.pan.2022.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 08/04/2022] [Accepted: 08/07/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Endoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk. METHODS The prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress. RESULTS ER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant. CONCLUSION This case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer.
Collapse
Affiliation(s)
- Makoto Kawamoto
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Takeichi Yoshida
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Koji Tamura
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Mohamad Dbouk
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Marcia Irene Canto
- Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | | | - Jin He
- Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Nicholas J Roberts
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Alison P Klein
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; The Sol Goldman Pancreatic Cancer Research Center, And the Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Michael Goggins
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
| |
Collapse
|
|
14
|
Wells JL, Haase CM, Rothwell ES, Naugle KG, Otero MC, Brown CL, Lai J, Chen KH, Connelly DE, Grimm KJ, Levenson RW, Fredrickson BL. Positivity resonance in long-term married couples: Multimodal characteristics and consequences for health and longevity. J Pers Soc Psychol 2022; 123:983-1003. [PMID: 35099204 PMCID: PMC9339047 DOI: 10.1037/pspi0000385] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The Positivity Resonance Theory of coexperienced positive affect describes moments of interpersonal connection characterized by shared positive affect, caring nonverbal synchrony, and biological synchrony. The construct validity of positivity resonance and its longitudinal associations with health have not been tested. The current longitudinal study examined whether positivity resonance in conflict interactions between 154 married couples predicts health trajectories over 13 years and longevity over 30 years. We used couples' continuous ratings of affect during the interactions to capture coexperienced positive affect and continuous physiological responses to capture biological synchrony between spouses. Video recordings were behaviorally coded for coexpressed positive affect, synchronous nonverbal affiliation cues (SNAC), and behavioral indicators of positivity resonance (BIPR). To evaluate construct validity, we conducted a confirmatory factor analysis to test a latent factor of positivity resonance encompassing coexperienced positive affect, coexpressed positive affect, physiological linkage of interbeat heart intervals, SNAC, and BIPR. The model showed excellent fit. To evaluate associations with health and longevity, we used dyadic latent growth curve modeling and Cox proportional hazards modeling, respectively, and found that greater latent positivity resonance predicted less steep declines in health and increased longevity. Associations were robust when accounting for initial health symptoms, sociodemographic characteristics, health-related behaviors, and individually experienced positive affect. We repeated health and longevity analyses, replacing latent positivity resonance with BIPR, and found consistent results. Findings validate positivity resonance as a multimodal construct, support the utility of the BIPR measure, and provide initial evidence for the characterization of positivity resonance as a positive health behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Collapse
Affiliation(s)
- Jenna L. Wells
- Department of Psychology, University of California, Berkeley
| | - Claudia M. Haase
- School of Education and Social Policy and (by courtesy) Department of Psychology, Northwestern University
| | - Emily S. Rothwell
- Department of Psychology, University of California, Davis
- Department of Psychological and Brain Sciences, University of Massachusetts, Amherst
| | | | - Marcela C. Otero
- Sierra Pacific Mental Illness Research Education and Clinical Centers, VA Palo Alto Healthcare System
- Department of Psychiatry and Behavioral Sciences, Stanford University
| | - Casey L. Brown
- Department of Psychology, University of California, Berkeley
| | - Jocelyn Lai
- Department of Psychological Science, University of California, Irvine
| | - Kuan-Hua Chen
- Department of Psychology, University of California, Berkeley
- Institute of Personality and Social Research, University of California, Berkeley
| | | | | | - Robert W. Levenson
- Department of Psychology, University of California, Berkeley
- Institute of Personality and Social Research, University of California, Berkeley
| | | |
Collapse
|
|
15
|
Yang WJ, Cao RC, Xiao W, Zhang XL, Xu H, Wang M, Zhou ZT, Chen HJ, Xu J, Chen XM, Zeng JL, Li SJ, Luo M, Han YJ, Yang XB, Feng GD, Lu YH, Ni YY, Wu CG, Bai JJ, Yuan ZQ, Jin J, Zhang GW. Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development. Cell Death Dis 2022; 13:893. [PMID: 36273194 PMCID: PMC9588032 DOI: 10.1038/s41419-022-05322-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 09/23/2022] [Accepted: 10/05/2022] [Indexed: 11/04/2022]
Abstract
Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.
Collapse
Affiliation(s)
- Wan-jun Yang
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong-chang Cao
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wang Xiao
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao-lou Zhang
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hao Xu
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Meng Wang
- grid.284723.80000 0000 8877 7471Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhi-tao Zhou
- grid.284723.80000 0000 8877 7471Department of the Electronic Microscope Room, Central Laboratory, Southern Medical University, Guangzhou, China
| | - Huo-ji Chen
- grid.284723.80000 0000 8877 7471School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Jia Xu
- grid.284723.80000 0000 8877 7471Department of Pathophysiology, Southern Medical University, Guangzhou, China
| | - Xue-mei Chen
- grid.284723.80000 0000 8877 7471Department of Occupational Health and Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jun-ling Zeng
- grid.284723.80000 0000 8877 7471Laboratory Animal Research Center of Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shu-ji Li
- grid.284723.80000 0000 8877 7471Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China
| | - Min Luo
- grid.284723.80000 0000 8877 7471Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yan-jiang Han
- grid.284723.80000 0000 8877 7471Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao-bing Yang
- grid.284723.80000 0000 8877 7471Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Institute, Guangzhou, China
| | - Guo-dong Feng
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Yu-heng Lu
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Yuan-yuan Ni
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Chan-gui Wu
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Jun-jie Bai
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Zi-qi Yuan
- grid.284723.80000 0000 8877 7471Southern Medical University, Guangzhou, China
| | - Jin Jin
- grid.284723.80000 0000 8877 7471Department of Gynaecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guo-wei Zhang
- grid.284723.80000 0000 8877 7471Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
16
|
Gao M, Guo Y, Li J, Chen X, Yuan Y, Ma W. The Clinicopathological Significance and Prognostic Value of PD-L2 in Patients with HCC, ICC and PAAD: A Meta-Analysis. INTERNATIONAL JOURNAL OF SURGERY: ONCOLOGY 2022. [DOI: 10.29337/ijsonco.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
|
|
17
|
Girodon E, Rebours V, Chen JM, Pagin A, Levy P, Ferec C, Bienvenu T. WITHDRAWN: Clinical interpretation of PRSS1 gene variants in patients with pancreatitis. Clin Res Hepatol Gastroenterol 2022; 46:101531. [PMID: 36057185 DOI: 10.1016/j.clinre.2020.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 08/27/2020] [Indexed: 02/04/2023]
Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published in Clinics and Research in Hepatology and Gastroenterology, Volume 45, Issue 1, 2021, 101497. https://doi.org/10.1016/j.clinre.2020.07.004. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal
Collapse
Affiliation(s)
- Emmanuelle Girodon
- Laboratoire de G..n..tique et Biologie Mol..culaires, H..pital Cochin, APHP.Centre-Universit.. de Paris, France
| | - Vinciane Rebours
- Service de Pancr..atologie-Gastroent..rologie, P..le des Maladies de l'Appareil Digestif, Universit.. Denis Diderot, H..pital Beaujon, APHP, DHU UNITY, Clichy, and Centre de R..f..rence des Maladies Rares du Pancr..as...PAncreaticRaresDISeases (PaRaDis), France
| | - Jian Min Chen
- INSERM UMR1078 "G..n..tique, G..nomique Fonctionnelle et Biotechnologies", EFS - Bretagne, Universit.. de Brest, CHRU Brest, Brest, France
| | - Adrien Pagin
- CHU Lille, Service de Toxicologie et G..nopathies, Lille, France
| | - Philippe Levy
- Service de Pancr..atologie-Gastroent..rologie, P..le des Maladies de l'Appareil Digestif, Universit.. Denis Diderot, H..pital Beaujon, APHP, DHU UNITY, Clichy, and Centre de R..f..rence des Maladies Rares du Pancr..as...PAncreaticRaresDISeases (PaRaDis), France
| | - Claude Ferec
- INSERM UMR1078 "G..n..tique, G..nomique Fonctionnelle et Biotechnologies", EFS - Bretagne, Universit.. de Brest, CHRU Brest, Brest, France
| | - Thierry Bienvenu
- Laboratoire de G..n..tique et Biologie Mol..culaires, H..pital Cochin, APHP.Centre-Universit.. de Paris, France.
| |
Collapse
|
|
18
|
Labiner AJ, Aronson A, Lucas AL. Screening and Surveillance for Pancreatic Adenocarcinoma in High-Risk Individuals. Hematol Oncol Clin North Am 2022; 36:929-942. [DOI: 10.1016/j.hoc.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
|
|
19
|
Abstract
Individuals at increased risk of developing pancreatic cancer, including those with a significant family history of the disease and those with pancreatic cancer susceptibility gene variants, can benefit from pancreas surveillance. Most pancreatic cancers diagnosed during surveillance are early-stage and such patients can achieve long-term survival. Determining who should undergo pancreas surveillance is still a work-in-progress, but the main tools clinicians use to estimate an individual's risk of pancreatic cancer are patient's age, the extent of their family history of pancreatic cancer, and whether or not they have a pancreatic cancer susceptibility gene mutation.
Collapse
Affiliation(s)
- Helena Saba
- Departments of Pathology, Johns Hopkins Medical Institutions, CRB2 351, 1550 Orleans Street, Baltimore, MD 21231, USA
| | - Michael Goggins
- Departments of Pathology, Johns Hopkins Medical Institutions, CRB2 351, 1550 Orleans Street, Baltimore, MD 21231, USA; Departments of Medicine, Johns Hopkins Medical Institutions, CRB2 351, 1550 Orleans Street, Baltimore, MD 21231, USA; Departments of Oncology, Johns Hopkins Medical Institutions, CRB2 351, 1550 Orleans Street, Baltimore, MD 21231, USA; Bloomberg School of Public Health, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, CRB2 351, 1550 Orleans Street, Baltimore, MD 21231, USA.
| |
Collapse
|
|
20
|
Mohindroo C, De Jesus-Acosta A, Yurgelun MB, Maitra A, Mork M, McAllister F. The Evolving Paradigm of Germline Testing in Pancreatic Ductal Adenocarcinoma and Implications for Clinical Practice. Surg Pathol Clin 2022; 15:491-502. [PMID: 36049831 DOI: 10.1016/j.path.2022.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Identification of deleterious germline mutations in pancreatic ductal adenocarcinoma (PDAC) patients can have therapeutic implications for the patients and result in cascade testing and prevention in their relatives. Universal testing for germline mutations is now considered standard of care in patients with PDAC, regardless of family history, personal history, or age. Here, we highlight the commonly identified germline mutations in PDAC patients as well as the impact of multigene panel testing. We further discuss therapeutic implications of germline testing on the index cases, and the impact of cascade testing on cancer early detection and prevention in relatives.
Collapse
Affiliation(s)
- Chirayu Mohindroo
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 1360, Houston, TX 77030, USA; Department of Internal Medicine, Sinai Hospital of Baltimore, 2435 W. Belvedere Ave, Ste 56, Baltimore, MD 21215, USA
| | - Ana De Jesus-Acosta
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, 401 North Broadway, Baltimore, MD 21231, USA
| | - Matthew B Yurgelun
- Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA
| | - Anirban Maitra
- Department of Translational Molecular Pathology, Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, 2130 West Holcombe Boulevard, Houston, TX 77030, USA
| | - Maureen Mork
- Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA
| | - Florencia McAllister
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 1360, Houston, TX 77030, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| |
Collapse
|
|
21
|
Han SY, Conwell DL, Diaz PT, Ferketich A, Jeon CY, Yadav D, Hart PA. The deleterious effects of smoking on the development and progression of chronic pancreatitis. Pancreatology 2022; 22:683-687. [PMID: 35981948 PMCID: PMC9474634 DOI: 10.1016/j.pan.2022.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/05/2022] [Accepted: 08/07/2022] [Indexed: 12/11/2022]
Affiliation(s)
- Samuel Y Han
- Division of Gastroenterology, Hepatology, and Nutrition. the Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Darwin L Conwell
- Department of Internal Medicine. University of Kentucky College of Medicine, Lexington, KY, USA
| | - Philip T Diaz
- Division of Pulmonary, Critical Care, and Sleep Medicine. the Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Amy Ferketich
- Division of Epidemiology. the Ohio State University College of Public Health, Columbus, OH, USA
| | - Christie Y Jeon
- Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Phil A Hart
- Division of Gastroenterology, Hepatology, and Nutrition. the Ohio State University Wexner Medical Center, Columbus, OH, USA.
| |
Collapse
|
|
22
|
Clinical and translational markers of severity and prognosis in chronic pancreatitis. Curr Opin Gastroenterol 2022; 38:501-508. [PMID: 35881973 DOI: 10.1097/mog.0000000000000868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW The incidence of chronic pancreatitis as a progressive inflammation and fibrosis syndrome is on the rise due to increasing awareness and improved imaging modalities. Numerous classification systems have been suggested in recent years to describe the disease, but only few of them have been used to classify the severity and prognostic significance of the disease. Biomarkers for severity and (early) chronic pancreatitis diagnosis are not yet ready for clinical application. RECENT FINDINGS In using the M-ANNHEIM and Chronic Pancreatitis Prognosis Score (COPPS) classification system, the severity assessment and short- and medium-term disease progression is available. A prospectively validated biomarker for early chronic pancreatitis diagnosis is not yet available, metabolome-based approaches seem to have the greatest potential for clinical translation. SUMMARY Currently, due to the lack of universal definition for the early disease stage of chronic pancreatitis, it is difficult to accurately classify these patient cohorts in existing scoring systems. In principle, setting up a suitable scoring system would allow surveillance and establish a therapy approaches flanked by corresponding biomarker panel development. Therapy management of chronic pancreatitis and monitoring by means of scoring systems (such as the COPPS) would make a decisive contribution to improving patient treatment.
Collapse
|
|
23
|
Abstract
Background It is estimated that about 10% of pancreatic cancer cases have a genetic background. People with a familial predisposition to pancreatic cancer can be divided into 2 groups. The first is termed hereditary pancreatic cancer, which occurs in individuals with a known hereditary cancer syndrome caused by germline single gene mutations (e.g., BRCA1/2, CDKN2A). The second is considered as familial pancreatic cancer, which is associated with several genetic factors responsible for the more common development of pancreatic cancer in certain families, but the precise single gene mutation has not been found. Aim This review summarizes the current state of knowledge regarding the risk of pancreatic cancer development in hereditary pancreatic cancer and familial pancreatic cancer patients. Furthermore, it gathers the latest recommendations from the three major organizations dealing with the prevention of pancreatic cancer in high-risk groups and explores recent guidelines of scientific societies on screening for pancreatic cancers in individuals at risk for hereditary or familial pancreatic cancer. Conclusions In order to improve patients’ outcomes, authors of current guidelines recommend early and intensive screening in patients with pancreatic cancer resulting from genetic background. The screening should be performed in excellence centers. The scope, extent and cost-effectiveness of such interventions requires further studies.
Collapse
|
|
24
|
Wu D, Bampton TJ, Scott HS, Brown A, Kassahn K, Drogemuller C, De Sousa SMC, Moore D, Ha T, Chen JWC, Khurana S, Torpy DJ, Radford T, Couper R, Palmer L, Coates PT. The clinical and genetic features of hereditary pancreatitis in South Australia. Med J Aust 2022; 216:578-582. [PMID: 35578795 PMCID: PMC9321757 DOI: 10.5694/mja2.51517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 12/30/2021] [Accepted: 01/07/2022] [Indexed: 11/24/2022]
Abstract
Objective To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia. Design, setting, participants Cross‐sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 – 30 June 2021. Main outcome measures Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis. Results We identified 44 people from ten families who received molecular diagnoses of hereditary pancreatitis during 2006–21 (including 25 Indigenous people [57%] and 27 women [61%]): 36 with PRSS1, five with SPINK1, and three with PRSS1 and SPINK1 mutations (determined by whole exome sequencing). Symptom onset before the age of ten years was reported by 37 people (84%). Pancreatitis‐related pain during the preceding four weeks was described as moderate or high by 35 people (79%); 38 people regularly used opioids (86%). Fifteen patients had diabetes mellitus (34%), and eight had undergone pancreatic surgery (18%). The estimated prevalence of hereditary pancreatitis was 1.1 (95% CI, 0.72–1.4) cases per 100 000 population for non‐Indigenous and 71 (95% CI, 66–77) cases per 100 000 population for Indigenous South Australians. Among people with adult‐onset chronic pancreatitis admitted to South Australian public hospitals during 2001–2019, the proportions of Indigenous people (12%) and women (38%) were smaller than we report for hereditary pancreatitis. Conclusion The estimated prevalence of hereditary pancreatitis in South Australia is higher than in Europe. PRSS1 gene mutations are important causes, particularly among Indigenous young people.
Collapse
Affiliation(s)
- Denghao Wu
- Adelaide Medical School University of Adelaide Adelaide SA
| | - Tristan J Bampton
- The University of Adelaide Adelaide SA
- Royal Adelaide Hospital Adelaide SA
| | | | - Alex Brown
- Aboriginal Health Research South Australian Health and Medical Research Institute Adelaide SA
- University of South Australia Adelaide SA
| | - Karin Kassahn
- Adelaide Medical School University of Adelaide Adelaide SA
- SA Pathology Adelaide SA
| | - Christopher Drogemuller
- Adelaide Medical School University of Adelaide Adelaide SA
- Royal Adelaide Hospital Adelaide SA
| | - Sunita MC De Sousa
- Adelaide Medical School University of Adelaide Adelaide SA
- Royal Adelaide Hospital Adelaide SA
| | - David Moore
- Women's and Children's Hospital Adelaide Adelaide SA
| | | | | | | | | | | | | | | | - P Toby Coates
- Adelaide Medical School University of Adelaide Adelaide SA
- Royal Adelaide Hospital Adelaide SA
| |
Collapse
|
|
25
|
Klatte DCF, Wallace MB, Löhr M, Bruno MJ, van Leerdam ME. Hereditary pancreatic cancer. Best Pract Res Clin Gastroenterol 2022; 58-59:101783. [PMID: 35988957 DOI: 10.1016/j.bpg.2021.101783] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/09/2021] [Accepted: 12/15/2021] [Indexed: 01/31/2023]
Abstract
Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.
Collapse
Affiliation(s)
- Derk C F Klatte
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, United States.
| | - Michael B Wallace
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, United States; Division of Gastroenterology and Hepatology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
| | - Matthias Löhr
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands.
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
| |
Collapse
|
|
26
|
Calderwood AH, Sawhney MS, Thosani NC, Rebbeck TR, Wani S, Canto MI, Fishman DS, Golan T, Hidalgo M, Kwon RS, Riegert-Johnson DL, Sahani DV, Stoffel EM, Vollmer CM, Al-Haddad MA, Amateau SK, Buxbaum JL, DiMaio CJ, Fujii-Lau LL, Jamil LH, Jue TL, Law JK, Lee JK, Naveed M, Pawa S, Storm AC, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: methodology and review of evidence. Gastrointest Endosc 2022; 95:827-854.e3. [PMID: 35183359 DOI: 10.1016/j.gie.2021.12.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/02/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Timothy R Rebbeck
- Harvard TH Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Marcia I Canto
- Division of Gastroenterology and Hepatology, Johns Hopkins Medicine, Baltimore, Maryland, USA
| | - Douglas S Fishman
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Talia Golan
- Cancer Center, Sheba Medical Center, Yehuda, Israel
| | - Manuel Hidalgo
- Division of Hematology and Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Douglas L Riegert-Johnson
- Department of Clinical Genomics and Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Dushyant V Sahani
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Elena M Stoffel
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Charles M Vollmer
- Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania, USA
| | - Mohammad A Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Stuart K Amateau
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, California, USA
| | - Christopher J DiMaio
- Department of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
| | - Larissa L Fujii-Lau
- Department of Gastroenterology, The Queen's Medical Center, Honolulu, Hawaii, USA
| | - Laith H Jamil
- Section of Gastroenterology and Hepatology, Beaumont Health, Royal Oak, Michigan, and Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
| | - Terry L Jue
- Department of Gastroenterology, The Permanente Medical Group, San Francisco, California, USA
| | - Joanna K Law
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA
| | - Mariam Naveed
- Advent Health Medical Group, Gastroenterology/Hepatology, Advent Health Hospital Altamonte Springs, Altamonte Springs, Florida, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Andrew C Storm
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| |
Collapse
|
|
27
|
Beyer G, Hoffmeister A, Michl P, Gress TM, Huber W, Algül H, Neesse A, Meining A, Seufferlein TW, Rosendahl J, Kahl S, Keller J, Werner J, Friess H, Bufler P, Löhr MJ, Schneider A, Lynen Jansen P, Esposito I, Grenacher L, Mössner J, Lerch MM, Mayerle J. S3-Leitlinie Pankreatitis – Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – September 2021 – AWMF Registernummer 021-003. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:419-521. [PMID: 35263785 DOI: 10.1055/a-1735-3864] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Georg Beyer
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
| | - Albrecht Hoffmeister
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Patrick Michl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Deutschland
| | - Wolfgang Huber
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Hana Algül
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Albrecht Neesse
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Deutschland
| | - Alexander Meining
- Medizinische Klinik und Poliklinik II Gastroenterologie und Hepatologie, Universitätsklinikum Würzburg, Deutschland
| | | | - Jonas Rosendahl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Stefan Kahl
- Klinik für Innere Medizin m. Schwerpkt. Gastro./Hämat./Onko./Nephro., DRK Kliniken Berlin Köpenick, Deutschland
| | - Jutta Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - Jens Werner
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, Deutschland
| | - Helmut Friess
- Klinik und Poliklinik für Chirurgie, Klinikum rechts der Isar, München, Deutschland
| | - Philip Bufler
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Deutschland
| | - Matthias J Löhr
- Department of Gastroenterology, Karolinska, Universitetssjukhuset, Stockholm, Schweden
| | - Alexander Schneider
- Klinik für Gastroenterologie und Hepatologie, Klinikum Bad Hersfeld, Deutschland
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Irene Esposito
- Pathologisches Institut, Heinrich-Heine-Universität und Universitätsklinikum Duesseldorf, Duesseldorf, Deutschland
| | - Lars Grenacher
- Conradia Radiologie München Schwabing, München, Deutschland
| | - Joachim Mössner
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Markus M Lerch
- Klinik für Innere Medizin A, Universitätsmedizin Greifswald, Deutschland.,Klinikum der Ludwig-Maximilians-Universität (LMU) München, Deutschland
| | - Julia Mayerle
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
| | | |
Collapse
|
|
28
|
[Diagnostics and clinical management of premalignant diseases of the pancreas]. Internist (Berl) 2022; 63:401-413. [PMID: 35234978 DOI: 10.1007/s00108-022-01308-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 10/19/2022]
Abstract
Pancreatic cancer is one of the most aggressive solid tumors and still has a poor prognosis. A delayed diagnosis at advanced stages and a poor response to systemic treatment frequently make a curative treatment impossible. Therefore, the identification of high-risk patients and screening them regularly is the most promising approach to improve the prognosis. Chronic pancreatitis as well as neoplastic pancreatic cysts can greatly increase the risk of developing pancreatic cancer. Furthermore, familial syndromes and germline mutations also confer an increased risk for development of pancreatic cancer. This article provides an overview of the various premalignant diseases of the pancreas. The value of the various imaging modalities, such as magnetic resonance imaging and endosonography are particularly discussed as well as the screening interval and the indications for surgical treatment are explained.
Collapse
|
|
29
|
Comparative Panel Sequencing of DNA Variants in cf-, ev- and tumorDNA for Pancreatic Ductal Adenocarcinoma Patients. Cancers (Basel) 2022; 14:cancers14041074. [PMID: 35205822 PMCID: PMC8870073 DOI: 10.3390/cancers14041074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/08/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. To improve treatment, personalized medicine uses next-generation DNA sequencing to monitor disease and guide treatment decisions. Tumor samples for sequencing are usually obtained by invasive fine-needle biopsy. Recently, the focus has been increasingly shifting to blood-based liquid biopsies, including circulating free (cf)DNA or DNA isolated from extracellular vesicles (evDNA). To evaluate the detection performance of DNA alterations, we directly compared tumor-, cf- and evDNA from patients with advanced PDAC upon panel sequencing. Copy number variations (CNVs), single nucleotide variants (SNVs) and insertions and deletions (indels) were compared for their concordance with tumorDNA. Compared to cfDNA, evDNA contained significantly larger DNA fragments, which improved the concordance of SNVs and indels with tumorDNA. In line with previous observations, CNV detection was mostly uninformative for cf- and evDNA. However, the combination of both liquid biopsy analytes was clearly superior for SNV detection, pointing to potentially improved actionable variant prediction. Abstract Pancreatic ductal adenocarcinomas (PDACs) are tumors with poor prognosis and limited treatment options. Personalized medicine aims at characterizing actionable DNA variants by next-generation sequencing, thereby improving treatment strategies and outcomes. Fine-needle tumor biopsies are currently the gold standard to acquire samples for DNA profiling. However, liquid biopsies have considerable advantages as they are minimally invasive and frequently obtainable and thus may help to monitor tumor evolution over time. However, which liquid analyte works best for this purpose is currently unclear. Our study aims to directly compare tumor-, circulating free (cf-) and extracellular vesicle-derived (ev)DNA by panel sequencing of matching patient material. We evaluated copy number variations (CNVs), single nucleotide variants (SNVs) and insertions and deletions (indels). Our data show that evDNA contains significantly larger DNA fragments up to 5.5 kb, in line with previous observations. Stringent bioinformatic processing revealed a significant advantage of evDNA with respect to cfDNA concerning detection performance for SNVs and a numerical increase for indels. A combination of ev- and cfDNA was clearly superior for SNV detection, as compared to either single analyte, thus potentially improving actionable variant prediction upon further optimization. Finally, calling of CNVs from liquid biopsies still remained challenging and uninformative.
Collapse
|
|
30
|
Kasuga A, Okamoto T, Udagawa S, Mori C, Mie T, Furukawa T, Yamada Y, Takeda T, Matsuyama M, Sasaki T, Ozaka M, Ueki A, Sasahira N. Molecular Features and Clinical Management of Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer. Int J Mol Sci 2022; 23:1205. [PMID: 35163129 PMCID: PMC8835700 DOI: 10.3390/ijms23031205] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/16/2022] [Accepted: 01/18/2022] [Indexed: 12/17/2022] Open
Abstract
Hereditary pancreatic cancers are caused by several inherited genes. Familial pancreatic cancer is defined as pancreatic cancer arising in a patient with at least two first-degree relatives with pancreatic cancer in the absence of an identified genetic cause. Hereditary pancreatic cancer syndromes and familial pancreatic cancers account for about 10% of pancreatic cancer cases. Germline mutations in BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, and TP53 and mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) are among the well-known inherited susceptibility genes. Currently available targeted medications include poly (ADP-ribose) polymerase inhibitors (PARP) for cases with mutant BRCA and immune checkpoint inhibitors for cases with mismatch repair deficiency. Loss of heterozygosity of hereditary pancreatic cancer susceptibility genes such as BRCA1/2 plays a key role in carcinogenesis and sensitivity to PARP inhibitors. Signature 3 identified by whole genome sequencing is also associated with homologous recombination deficiency and sensitivity to targeted therapies. In this review, we summarize molecular features and treatments of hereditary pancreatic cancer syndromes and surveillance procedures for unaffected high-risk cases. We also review transgenic murine models to gain a better understanding of carcinogenesis in hereditary pancreatic cancer.
Collapse
Affiliation(s)
- Akiyoshi Kasuga
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Takeshi Okamoto
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Shohei Udagawa
- Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan;
| | - Chinatsu Mori
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Takafumi Mie
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Takaaki Furukawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Yuto Yamada
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Masato Matsuyama
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| | - Arisa Ueki
- Department of Clinical Genetics, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan;
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan; (T.O.); (C.M.); (T.M.); (T.F.); (Y.Y.); (T.T.); (M.M.); (T.S.); (M.O.); (N.S.)
| |
Collapse
|
|
31
|
Panchoo AV, VanNess GH, Rivera-Rivera E, Laborda TJ. Hereditary pancreatitis: An updated review in pediatrics. World J Clin Pediatr 2022; 11:27-37. [PMID: 35096544 PMCID: PMC8771313 DOI: 10.5409/wjcp.v11.i1.27] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/08/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Hereditary Pancreatitis (HP) has emerged as a significant cause of acute, acute recurrent and chronic pancreatitis in the pediatric population. Given that it presents similarly to other causes of pancreatitis, a positive family history and/or isolation of a gene mutation are vital in its designation. Inheritance patterns remain complex, but mutations involving the PRSS1, SPINK1, CFTR and CTRC genes are commonly implicated. Since being first described in 1952, dozens of genetic alterations that modify the action of pancreatic enzymes have been identified. Among children, these variants have been isolated in more than 50% of patients with chronic pancreatitis. Recent research has noted that such mutations in PRSS1, SPINK1 and CFTR genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis. Patients with HP are at increased risk of developing diabetes mellitus, exocrine pancreatic insufficiency, and pancreatic adenocarcinoma. Management follows a multi-disciplinary approach with avoidance of triggers, surveillance of associated conditions, treatment of pancreatic insufficiency and use of endoscopic and surgical interventions for complications. With significant sequela, morbidity and a progressive nature, a thorough understanding of the etiology, pathophysiologic mechanisms, diagnostic evaluation, current management strategies and future research considerations for this evolving disease entity in pediatrics is warranted.
Collapse
Affiliation(s)
- Arvind Vasant Panchoo
- Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of San Antonio, San Antonio, TX 78207, United States
- Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, United States
| | - Grant H VanNess
- Faculty of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Edgardo Rivera-Rivera
- Department of Pediatric Gastroenterology, Parkview Health, Fort Wayne, IN 46845, United States
| | - Trevor J Laborda
- Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of San Antonio, San Antonio, TX 78207, United States
- Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, United States
| |
Collapse
|
|
32
|
Abstract
Hereditary pancreatitis (HP) is a rare inherited chronic pancreatitis (CP) with strong genetic associations, with estimated prevalence ranging from 0.3 to 0.57 per 100,000 across Europe, North America, and East Asia. Apart from the most well-described genetic variants are PRSS1, SPINK1, and CFTR, many other genes, such as CTRC, CPA1, and CLDN2 and CEL have been found to associate with HP, typically in one of the 3 main mechanisms such as altered trypsin activity, pancreatic ductal cell secretion, and calcium channel regulation. The current mainstay of management for patients with HP comprises genetic testing for eligible individuals and families, alcohol and tobacco cessation avoidance, pain control, and judicious screening for complications, including exocrine and endocrine insufficiency and pancreatic cancer.
Collapse
Affiliation(s)
- Yichun Fu
- Henry D. Janowitz Division of Gastroenterology, One Gustave L. Levy Place, Box 1069, New York, NY 10029, USA; Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Aimee L Lucas
- Henry D. Janowitz Division of Gastroenterology, One Gustave L. Levy Place, Box 1069, New York, NY 10029, USA; Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
| |
Collapse
|
|
33
|
Kim K, Gaddam S, Liu Q. Pathogenesis, Epidemiology, and Prognosis of Pancreatic Adenocarcinomas. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:461-481. [DOI: 10.1007/978-3-030-41683-6_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
34
|
Kawamoto M, Kohi S, Abe T, Dbouk M, Macgregor-Das A, Koi C, Song KB, Borges M, Sugimine R, Laheru D, Hruban RH, Roberts N, Klein AP, Goggins M. Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis. Int J Cancer 2021; 150:1123-1133. [PMID: 34817877 DOI: 10.1002/ijc.33883] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 10/25/2021] [Accepted: 11/12/2021] [Indexed: 12/16/2022]
Abstract
Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio [OR]: 3.80 [1.92-7.51], P = .0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 [0.88-6.58], P = .087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 [2.74-18.01], P = .0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58-8.39], P < .023) and CPB1 (OR: 9.51 [3.46-26.15], P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.
Collapse
Affiliation(s)
- Makoto Kawamoto
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Shiro Kohi
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Toshiya Abe
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Mohamad Dbouk
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Anne Macgregor-Das
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Chiho Koi
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Ki-Byung Song
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Michael Borges
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Ryo Sugimine
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Daniel Laheru
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Nicholas Roberts
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Alison P Klein
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Bloomberg School of Public Health, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Michael Goggins
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| |
Collapse
|
|
35
|
Lin L, Li Z, Yan L, Liu Y, Yang H, Li H. Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990-2019. J Hematol Oncol 2021; 14:197. [PMID: 34809683 PMCID: PMC8607714 DOI: 10.1186/s13045-021-01213-z] [Citation(s) in RCA: 200] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/01/2021] [Indexed: 12/20/2022] Open
Abstract
Background and aims Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control.
Methods Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types. Results In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally. Conclusions The global cancer burden continues to increase, with substantial mortality and morbidity differences among the different regions, ages, countries, gender, and cancer types. Effective and locally tailored cancer prevention and control measures are essential in reducing the global cancer burden in the future. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01213-z.
Collapse
Affiliation(s)
- Longfei Lin
- Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhiyong Li
- Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China
| | - Lei Yan
- Fengtai District Community Health Center, Beijing, China
| | - Yuling Liu
- Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongjun Yang
- Experimental Medical Center, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Hui Li
- Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, China.
| |
Collapse
|
|
36
|
Biller LH, Wolpin BM, Goggins M. Inherited Pancreatic Cancer Syndromes and High-Risk Screening. Surg Oncol Clin N Am 2021; 30:773-786. [PMID: 34511196 DOI: 10.1016/j.soc.2021.06.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pancreatic cancer is the third leading cause of cancer death in the United States, with a 5-year survival rate of 9%. Individuals with inherited pancreatic cancer syndromes are at an increased risk for developing pancreatic cancer and may benefit from pancreatic cancer surveillance with the goal to detect and intervene on early-stage cancer or high-risk precursor lesions. Given the screening implications for family members and therapeutic implications for probands, all patients diagnosed with pancreatic cancer are recommended to undergo germline genetic testing.
Collapse
Affiliation(s)
- Leah H Biller
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, USA. https://twitter.com/leahbillermd
| | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, USA.
| | - Michael Goggins
- Johns Hopkins University, 1550 Orleans Street, Baltimore, MD, USA.
| |
Collapse
|
|
37
|
Ali AF, Liu J, Shang S, Chen Y. Multidisciplinary treatment of chronic active Epstein-Barr virus infection with multiple complications: a case report. Transl Pediatr 2021; 10:2402-2406. [PMID: 34733681 PMCID: PMC8506058 DOI: 10.21037/tp-21-154] [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: 04/07/2021] [Accepted: 06/17/2021] [Indexed: 11/06/2022] Open
Abstract
Chronic active Epstein-Barr virus (CAEBV) infection is a very rare and potentially life-threatening illness caused by long-term EBV infection. Globally, the prevalence is the highest among young children and adolescents with increased frequency in Asians and Native Americans, whereas it is sporadically encountered in European countries. Typically, patients present with nonspecific symptoms such as fever, lymphadenopathy, hepatosplenomegaly, and liver dysfunction. However, the complications of CAEBV and its treatment are quite complex and require great care. We report a case of a 3-year-old boy with CAEBV infection who was later diagnosed with pancreatic mass and recurrent pancreatitis. A multidisciplinary board was consulted for correct diagnosis and treatment plan making. The treatment included pharmaceutical and surgical (duodenum-preserving pancreatic head resection) approaches. The patient showed tremendous improvement following the third discharge from the hospital and is still free of any symptoms. In this case report, we discuss differential diagnosis and comprehensively examined the possibility of the development of pancreatitis caused by EBV infection, the possibility of autoimmune pancreatitis, and the possibility of hereditary pancreatitis. To confirm or rule out the first two etiologies, laboratory and pathology results were studied. We also performed exon sequencing using Agilent exome capture kit to rule out hereditary pancreatitis. The clinical course of this disease and the way it was handled deserves attention so that similar cases receive prompt treatment.
Collapse
Affiliation(s)
- Ahmed Faisal Ali
- Department of Infectious Diseases, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Juanjuan Liu
- Department of Infectious Diseases, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shiqiang Shang
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yinghu Chen
- Department of Infectious Diseases, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
38
|
Huang W, Xue L, Xu H, Kong Z, Xu J, Zhao H, Nie Y. Diagnostic value of neuronal pentraxin II methylation in patients with pancreatic cancer: Meta-analysis. Int J Clin Pract 2021; 75:e14443. [PMID: 34105851 DOI: 10.1111/ijcp.14443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/01/2020] [Accepted: 05/24/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Pancreatic cancer (PC) is a devasting disease of which mortality almost parallels its incidence. PC tissue may express aberrantly methylated neuronal pentraxin II (NPTX2), but it is unclear what the consequences of this are. METHODS We systematically searched PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), from inception to July 15, 2020, to identify if the detection of methylated NPTX2 have sufficient sensitivity and specificity to identify PC from other benign pancreatic diseases. RESULTS Majority of the studies obtained samples from pancreatic juice by endoscopy or surgery and composed of population with chronic pancreatitis, benign cystic lesion, intraductal papillary mucinous neoplasm, and healthy controls. Our results demonstrated that the diagnostic value of methylated NPTX2 is of widely various sensitivity and specificity and it shown higher specificity in differentiate PC from benign diseases. The lab method of quantitative real-time methylation-specific PCR (QMSP) has higher specificity than real-time methylation-specific PCR (MSP) in detecting the indicator. CONCLUSIONS NPTX2 methylation could serve as a promising molecular biomarker for pancreatic cancer diagnosis, for its high diagnostic value in differentiating pancreatic cancer from benign pancreatic disease with the lab method. The variable sensitivity of methylated NPTX2 was multifactorial, and it must be promoted before applied as screening test in clinical practice. Furthermore, experiments on methylated NPTX2 were needed to expanded for lower the heterogeneity.
Collapse
Affiliation(s)
- Wenqi Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - LiFeng Xue
- Department of Gastroenterology, People's Hospital of Shenzhen, Guangzhou, China
| | - Haoming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Zhiqian Kong
- Dongguan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Dongguan, China
| | - Jing Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hailan Zhao
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| |
Collapse
|
|
39
|
Abstract
OBJECTIVES Fatty pancreas (FP), previously believed to be without clinical significance, recently has been shown to be associated with comorbid diseases. We aimed to explore whether FP predispose to acute pancreatitis. METHODS Patients who underwent endoscopic ultrasound for hepatobiliary indications were included. Patients with pathological pancreato-biliary findings other than FP were excluded. The cohort was divided into patients with a history of pancreatitis (within 6 months of endoscopic ultrasound, group A) and patients without (group B). RESULTS Overall, 189 patients were included. Sixty-one (32.3%) patients were in group A, and 128 (67.7%) patients were in group B. The average age in group A was 55.5 (standard deviation, 17.7) versus 58.5 (standard deviation, 13.5) in group B. The prevalence of FP in group A (37.7%) was higher compared with group B (4.7%) (P = 0.001). On univariate analysis, FP showed significant correlation with a history of acute pancreatitis [odds ratio (OR), 5.14, P = 0.006] and hyperlipidemia (OR, 4.19; P = 0.002). On multivariate analysis, FP remained significantly associated with a history of acute pancreatitis after stratification for obesity and hyperlipidemia (OR, 10.78; 95% confidence interval, 3.75-30.89; P < 0.0001). CONCLUSIONS Fatty pancreas was associated with acute pancreatitis. Clinicians should be aware of this association.
Collapse
|
|
40
|
Ru N, Wu SY, Wang L, Zhu JH, Xu XN, Guo JY, Hu LH, Li ZS, Zou WB, Liao Z. SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort. Pancreatology 2021; 21:848-853. [PMID: 34140232 DOI: 10.1016/j.pan.2021.05.304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 05/27/2021] [Accepted: 05/30/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). METHODS This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. RESULTS PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. CONCLUSIONS CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.
Collapse
Affiliation(s)
- Nan Ru
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Sheng-Yong Wu
- Department of Health Statistics, Naval Medical University, Shanghai, China
| | - Lei Wang
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Jia-Hui Zhu
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Xiao-Nan Xu
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Ji-Yao Guo
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Liang-Hao Hu
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Wen-Bin Zou
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China.
| | - Zhuan Liao
- Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, Naval Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China.
| |
Collapse
|
|
41
|
Kalayarasan R, Narayanan S, Sahoo J, Mohan P. Impact of surgery for chronic pancreatitis on the risk of pancreatic cancer: Untying the Gordian knot. World J Gastroenterol 2021; 27:4371-4382. [PMID: 34366610 PMCID: PMC8316902 DOI: 10.3748/wjg.v27.i27.4371] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/10/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma is an aggressive tumor with poor long-term outcomes. Chronic pancreatitis (CP) is considered a risk factor for the development of pancreatic cancer (PC). Persistent pancreatic inflammation and activation of pancreatic stellate cells play a crucial role in the pathogenesis of CP-related PC by activating the oncogene pathway. While genetic mutations increase the possibility of recurrent and persistent pancreatic inflammation, they are not directly associated with the development of PC. Recent studies suggest that early surgical intervention for CP might have a protective role in the development of CP-related PC. Hence, the physician faces the clinical question of whether early surgical intervention should be recommended in patients with CP to prevent the development of PC. However, the varying relative risk of PC in different subsets of CP underlines the complex gene-environment interactions in the disease pathogenesis. Hence, it is essential to stratify the risk of PC in each individual patient. This review focuses on the complex relationship between CP and PC and the impact of surgical intervention on PC risk. The proposed risk stratification based on the genetic and environmental factors could guide future research and select patients for prophylactic surgery.
Collapse
Affiliation(s)
- Raja Kalayarasan
- Department of Surgical Gastroenterology, JIPMER, Puducherry 605006, India
| | - Sankar Narayanan
- Department of Surgical Gastroenterology, JIPMER, Puducherry 605006, India
| | | | - Pazhanivel Mohan
- Department of Medical Gastroenterology, JIPMER, Puducherry 605006, India
| |
Collapse
|
|
42
|
Abstract
Pancreatic cancer is a genetic disease, and the recurrent genetic alterations characteristic of pancreatic cancer indicate the cellular processes that are targeted for malignant transformation. In addition to somatic alterations in the most common driver genes (KRAS, CDKN2A, TP53 and SMAD4), large-scale studies have revealed major roles for genetic alterations of the SWI/SNF and COMPASS complexes, copy number alterations in GATA6 and MYC that partially define phenotypes of pancreatic cancer, and the role(s) of polyploidy and chromothripsis as factors contributing to pancreatic cancer biology and progression. Germline variants that increase the risk of pancreatic cancer continue to be discovered along with a greater appreciation of the features of pancreatic cancers with mismatch repair deficiencies and homologous recombination deficiencies that confer sensitivity to therapeutic targeting. Wild-type KRAS pancreatic cancers, some of which are driven by alternative oncogenic events affecting NRG1 or NTRK1 - for which targeted therapies exist - further underscore that pancreatic cancer is formally entering the era of precision medicine. Given the vast developments within this field, here we review the wide-ranging and most current information related to pancreatic cancer genomics with the goal of integrating this information into a unifying description of the life history of pancreatic cancer.
Collapse
|
|
43
|
Cai J, Chen H, Lu M, Zhang Y, Lu B, You L, Zhang T, Dai M, Zhao Y. Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett 2021; 520:1-11. [PMID: 34216688 DOI: 10.1016/j.canlet.2021.06.027] [Citation(s) in RCA: 224] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 06/09/2021] [Accepted: 06/25/2021] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer.
Collapse
Affiliation(s)
- Jie Cai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Hongda Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Ming Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Yuhan Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Bin Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| |
Collapse
|
|
44
|
Keihanian T, Barkin JA, Souto EO. Early Detection of Pancreatic Cancer: Risk Factors and the Current State of Screening Modalities. Gastroenterol Hepatol (N Y) 2021; 17:254-262. [PMID: 34776799 PMCID: PMC8576846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Pancreatic cancer (PC) is expected to become the second leading cause of cancer-related mortality in the United States within the next decade. Patients often present at late stages of the disease, when they become symptomatic; in many cases, these patients have unresectable disease that is associated with a poor prognosis. Considering the low incidence of PC in the general population, routine screening of average-risk individuals is not feasible and not recommended. Individuals with familial germline mutations or familial PC are at higher risk of developing PC. Improving detection of PC at an earlier stage entails the recognition of high-risk individuals who may benefit from a long-term screening program. This article identifies patients who may be at increased risk of developing PC, discusses PC screening recommendations, and compares imaging-based modalities and biomarkers for early detection of PC.
Collapse
Affiliation(s)
- Tara Keihanian
- Department of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida
| | - Jodie A Barkin
- Department of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida
| | - Enrico O Souto
- Department of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida
| |
Collapse
|
|
45
|
Bampton TJ, Holmes-Walker DJ, Drogemuller CJ, Radford T, Anderson P, Etherton C, Russell CH, Khurana S, Torpy DJ, Couper JJ, Couper RLT, Macintyre P, Neo EL, Benitez-Aguirre P, Thomas G, Loudovaris T, Thomas HE, Palmer LJ, Wu D, Rogers NM, Williams L, Hawthorne WJ, O'Connell PJ, Kay TW, Pleass H, Chen JW, Coates PT. Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis. ANZ J Surg 2021; 91:2663-2668. [PMID: 33956377 DOI: 10.1111/ans.16853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.
Collapse
Affiliation(s)
- Tristan J Bampton
- Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.,The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - D Jane Holmes-Walker
- Department of Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia.,Westmead Institute for Medical Research, Sydney, New South Wales, Australia
| | - Chris J Drogemuller
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Toni Radford
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Patricia Anderson
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia
| | - C Etherton
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - C H Russell
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - S Khurana
- Department of Gastroenterology, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - David J Torpy
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - J J Couper
- Department of Gastroenterology, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - R L T Couper
- Department of Gastroenterology, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - Pamela Macintyre
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - E L Neo
- Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Paul Benitez-Aguirre
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - G Thomas
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.,Westmead Children's Hospital, Sydney, New South Wales, Australia
| | - T Loudovaris
- Islet biology, St Vincent's Institute, Melbourne, Victoria, Australia
| | - H E Thomas
- Islet biology, St Vincent's Institute, Melbourne, Victoria, Australia
| | - Lyle J Palmer
- School of Public Health, The University of Adelaide, Adelaide, South Australia, Australia
| | - Denghao Wu
- Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
| | - Natasha M Rogers
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia.,Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia
| | - L Williams
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia
| | - W J Hawthorne
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia.,Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia.,Department of Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | - P J O'Connell
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia.,Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia
| | - Tom W Kay
- Islet biology, St Vincent's Institute, Melbourne, Victoria, Australia
| | - Henry Pleass
- Westmead Institute for Medical Research, Sydney, New South Wales, Australia.,Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.,Department of Renal Medicine, Westmead Hospital, Sydney, New South Wales, Australia.,Department of Surgery, Westmead Hospital, Sydney, New South Wales, Australia
| | - John W Chen
- The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia.,Department of Gastroenterology, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - P Toby Coates
- Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.,The Central and Northern Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | | |
Collapse
|
|
46
|
Khalaf N, El-Serag HB, Abrams HR, Thrift AP. Burden of Pancreatic Cancer: From Epidemiology to Practice. Clin Gastroenterol Hepatol 2021; 19:876-884. [PMID: 32147593 PMCID: PMC8559554 DOI: 10.1016/j.cgh.2020.02.054] [Citation(s) in RCA: 188] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 02/05/2020] [Accepted: 02/28/2020] [Indexed: 12/24/2022]
Abstract
Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with 432,242 related deaths in 2018. Unlike other cancers, the incidence of pancreatic cancer continues to increase, with little improvement in survival rates. We review the epidemiologic features of pancreatic cancer, covering surveillance and early detection in high-risk persons. We summarize data on worldwide incidence and mortality and analyze the 1975-2016 data from 9 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results study, on the overall burden of pancreatic cancer as well as age-, sex-, and race-specific incidence, survival rates and trends. It is important to increase our knowledge of the worldwide and regional epidemiologic features of and risk factors for pancreatic cancer, to identify new approaches for prevention, surveillance, and treatment.
Collapse
Affiliation(s)
- Natalia Khalaf
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Hannah R Abrams
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| |
Collapse
|
|
47
|
Hereditary pancreatitis in childhood: course of disease and complications. Wien Klin Wochenschr 2021; 133:669-673. [PMID: 33909107 DOI: 10.1007/s00508-021-01869-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 03/31/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Hereditary pancreatitis is rare. Pain therapy for juvenile symptom onset, child development and the risk of pancreatic carcinoma in adulthood must be considered. PATIENTS, MATERIAL AND METHODS Data from a cohort of 11 patients with disease onset in childhood (< 16 years) were analyzed retrospectively. The gene encoding cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1) and cystic fibrosis transmembrane conductance regulator (CFTR) genes were investigated as genetic factors. Treatment concept and complications were registered. Prognosis, treatment success and quality of life were objectified using the chronic pancreatitis prognosis score and a standardized questionnaire (KIDSCREEN-10 index). RESULTS The mean age of symptom onset was 7.5 ±4.2 years. The PRSS1 and SPINK1 mutations each occurred with 36.4%, 3 patients had a pancreas divisum and 2 a long common channel. The course of pancreatitis was obstructive in 90.9%. Exocrine pancreatic insufficiency occurred in seven patients so far (mean age 12.5 years). Stenting was performed in 72.7% and 18.2% needed pancreatic surgery. Currently the chronic prognosis score is on average 7.5 points, pain on numerical rating scale 0 (no pain). The mean KIDSCREEN‑T score of 66.9 confirms a very good quality of life. CONCLUSION Patients with genetically caused chronic pancreatitis are rare. Their care ranges from pain therapy in childhood and adolescence to questions concerning family planning and pancreatic cancer prevention from mid-adulthood onward. The disease is challenging for the interdisciplinary cooperation. We found the step-up strategy to be a good option for pain therapy. A national registry monitored by scientific societies with active recruitment for screening examinations will further improve and ensure care in the long term.
Collapse
|
|
48
|
Freeman AJ, Maqbool A, Bellin MD, Goldschneider KR, Grover AS, Hartzell C, Piester TL, Szabo F, Kiernan BD, Khalaf R, Kumar R, Rios M, Husain SZ, Morinville VD, Abu-El-Haija M. Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr 2021; 72:324-340. [PMID: 33230082 PMCID: PMC8054312 DOI: 10.1097/mpg.0000000000003001] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
ABSTRACT This position paper summarizes the current understanding of the medical management of chronic pancreatitis (CP) in children in light of the existing medical literature, incorporating recent advances in understanding of nutrition, pain, lifestyle considerations, and sequelae of CP. This article complements and is intended to integrate with parallel position papers on endoscopic and surgical aspects of CP in children. Concepts and controversies related to pancreatic enzyme replacement therapy (PERT), the use of antioxidants and other CP medical therapies are also reviewed. Highlights include inclusion of tools for medical decision-making for PERT, CP-related diabetes, and multimodal pain management (including an analgesia ladder). Gaps in our understanding of CP in children and avenues for further investigations are also reviewed.
Collapse
Affiliation(s)
- A. Jay Freeman
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA
| | - Asim Maqbool
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Melena D. Bellin
- Department of Pediatrics, Division of Endocrinology and Diabetes, University of Minnesota Masonic Children’s Hospital, Minneapolis, MN
| | | | - Amit S. Grover
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Cheryl Hartzell
- Division of Pediatric Anesthesiology, Department of Anesthesiology, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA
| | - Travis L. Piester
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA
| | - Flora Szabo
- Division of Pediatric Gastroenterology and Nutrition, Children’s Hospital of Richmond, Virginia Commonwealth University, Richmond, VA
| | - Bridget Dowd Kiernan
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Racha Khalaf
- Digestive Health Institute, Children’s Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, CO
| | - Rakesh Kumar
- Department of Gastroenterology, Hepatology and Nutrition, Promedica Toledo Children’s Hospital, Toledo, OH
| | - Mirta Rios
- Food and Nutrition Department, Nicklaus Children’s Hospital, Miami, FL
| | - Sohail Z. Husain
- Department of Pediatrics, Stanford University, and the Lucile Packard Children’s Hospital, Palo Alto, CA
| | - Veronique D. Morinville
- Division of Pediatric Gastroenterology and Nutrition, Montreal Children’s Hospital, McGill University Health Center, Montreal, Quebec, Canada
| | - Maisam Abu-El-Haija
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| |
Collapse
|
|
49
|
Clinical interpretation of PRSS1 variants in patients with pancreatitis. Clin Res Hepatol Gastroenterol 2021; 45:101497. [PMID: 33257277 DOI: 10.1016/j.clinre.2020.07.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/01/2020] [Indexed: 02/04/2023]
Abstract
Since the description of the PRSS1 gene encoding the cationic trypsinogen as being involved in dominant hereditary pancreatitis, more than 50 PRSS1 variants have been reported. Among the PRSS1 variants that have been classified as pathogenic, some have a high penetrance and others have a low penetrance. Assessing the clinical relevance of PRSS1 variants is often complicated in the absence of functional evidence and interpretation of rare variants is not very easy in clinical practice. The aim of this study was to review the different variants identified in the PRSS1 gene and to classify them according to their degree of deleterious effect. This classification was based on the results of several in vitro experiments and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected individuals. This review should help geneticists and clinicians in charge of patient's care and genetic counseling to interpret molecular results.
Collapse
|
|
50
|
Genetic Abnormalities in Pancreatitis: An Update on Diagnosis, Clinical Features, and Treatment. Diagnostics (Basel) 2020; 11:diagnostics11010031. [PMID: 33375361 PMCID: PMC7824215 DOI: 10.3390/diagnostics11010031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/12/2020] [Accepted: 12/22/2020] [Indexed: 02/07/2023] Open
Abstract
Several pancreatitis susceptibility genes have been identified to date. A relationship between a mutation in the cationic trypsinogen (protease serine 1, PRSS1) gene and hereditary pancreatitis (HP) was first identified in 1996. Currently, HP has been defined as either two or more individuals within a family exhibiting pancreatitis for two or more generations, or pancreatitis linked to mutation of the PRSS1 gene. In 2000, a mutation in the serine protease inhibitor gene (Kazal type 1: SPINK1) was reported to be related to sporadic pancreatitis of unknown etiology. This paper reviews and summarizes the current published data on the pancreatitis susceptibility genes, mainly PRSS1 and SPINK1 genes, and introduces a diagnostic and therapeutic approach for dealing with patients with these gene mutations. Patients with these genetic predispositions, both children and adults, have often been initially diagnosed with idiopathic acute pancreatitis, in approximately 20-50% of pediatric cases and 28-80% of adult cases. In such patients, where the etiology is unknown, genetic testing, which requires pre-test and post-test genetic counselling, may prove helpful. Patients with chronic pancreatitis (CP) due to SPINK1 gene mutation and HP patients have a potentially high risk of pancreatic exocrine insufficiency, diabetes mellitus, and, of particular importance, pancreatic cancer. Thus, these patients require careful long-term follow-up and management. Specifically, symptomatic CP patients often need endoscopic therapy or surgery, often following a step-up approach beginning with endoscopic therapy and progressing to surgery if necessary, which is similar to the therapeutic approach for patients with CP due to other etiologies. It is important that clinicians are aware of the characteristics of patients with pancreatitis susceptibility genetic abnormalities.
Collapse
|