|
1
|
Testoni PA, Testoni S. Endoscopic Management of Recurrent Acute Pancreatitis. J Clin Med 2025; 14:2150. [PMID: 40217601 PMCID: PMC11989922 DOI: 10.3390/jcm14072150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/28/2025] [Accepted: 03/05/2025] [Indexed: 04/14/2025] Open
Abstract
This review aims to summarize the role of endoscopic therapy in the management and outcomes of recurrent acute pancreatitis (RAP). RAP is a clinical entity characterized by repeated episodes of acute pancreatitis in the setting of a normal gland or chronic pancreatitis (CP). The aetiology of RAP can be identified in about 70% of cases; for the remaining cases, the term "idiopathic" (IRAP) is used. However, advanced diagnostic techniques may reduce the percentage of IRAP to 10%. Recognized causes of RAP are gallstone disease, including microlithiasis and biliary sludge, sphincter of Oddi dysfunction (SOD), pancreatic ductal abnormalities (either congenital or acquired) interfering with pancreatic juice or bile outflow, genetic mutations, and alcohol consumption. SOD, as a clinical entity, was recently revised in the Rome IV consensus, which only recognized type 1 dysfunction as a true pathological condition, while type 2 SOD was defined as a suspected functional biliary sphincter disorder requiring the documentation of elevated basal sphincter pressure to be considered a true clinical entity and type 3 was abandoned as a diagnosis and considered functional pain. Endoscopic therapy by retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) has been proven effective when a mechanical obstruction is found and can be removed. If an obstruction is not documented, few treatment options are available to prevent the recurrence of pancreatitis and progression toward chronic disease. In gallstone disease, endoscopic biliary sphincterotomy (EBS) is effective when a dilated common bile duct or biliary sludge/microlithiasis is documented. In type 1 SOD, biliary or dual sphincterotomy is generally successful, while in type 2 SOD, endotherapy should be reserved for patients with documented sphincter dysfunction. However, in recent years, doubts have been expressed about the real efficacy of sphincterotomy in this setting. When sphincter dysfunction is not confirmed, endotherapy should be discouraged. In pancreas divisum (PD), minor papilla sphincterotomy is effective when there is a dilated dorsal duct, and the success rate is the highest in RAP patients. In the presence of obstructive conditions of the main pancreatic duct, pancreatic endotherapy is generally successful if RAP depends on intraductal hypertension. However, despite the efficacy of endotherapy, progression toward CP has been shown in some of these patients, mainly in the presence of PD, very likely depending on underlying genetic mutations. In patients with IRAP, the real utility of endotherapy still remains unclear; this is because several unknown factors may play a role in the disease, and data on outcomes are few, frequently contradictory or uncontrolled, and, in general, limited to a short period of time.
Collapse
Affiliation(s)
- Pier Alberto Testoni
- Gastroenterology and Gastrointestinal Endoscopy, La Madonnina Clinic, Vita-Salute San Raffaele University, 20100 Milan, Italy
| | - Sabrina Testoni
- Unit of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Policlinico San Donato, Vita-Salute San Raffaele University, 20100 Milan, Italy;
| |
Collapse
|
|
2
|
Parra Villasmil MG, Bellin MD. Risk Factors and Mechanisms for Diabetes in Pancreatitis. Gastroenterol Clin North Am 2025; 54:175-188. [PMID: 39880526 PMCID: PMC11780253 DOI: 10.1016/j.gtc.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Diabetes (DM) can occur as a complication of acute, acute recurrent, or chronic pancreatitis, affecting more than 30% of adults with chronic pancreatitis. Data on the pathophysiology and management are limited, especially in pediatric population. Proposed mechanisms include insulin deficiency, insulin resistance, decreased pancreatic polypeptide, and possible beta-cell autoimmunity (in a small subset). Risk factors for developing diabetes in those with pancreatitis may include hypertriglyceridemia, obesity, necrotizing pancreatitis, exocrine pancreatic insufficiency, and pancreatic calcifications, among others. Further studies are required to understand pathophysiology of pancreatogenic DM, in order to define optimal treatment approaches.
Collapse
Affiliation(s)
- María Graciela Parra Villasmil
- Department of Pediatrics, Stead Family Children's Hospital, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Melena D Bellin
- Department of Pediatrics, University of Minnesota, MMC 391, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
| |
Collapse
|
|
3
|
Mohamed G, Munir M, Rai A, Gaddam S. Pancreatic Cancer: Screening and Early Detection. Gastroenterol Clin North Am 2025; 54:205-221. [PMID: 39880528 DOI: 10.1016/j.gtc.2024.09.006] [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] [Indexed: 01/31/2025]
Abstract
Pancreatic cancer, often diagnosed at advanced stages, has poor survival rates. Effective screening aims to detect the disease early, improving outcomes. Current guidelines recommend screening high-risk groups, including those with a family history or genetic predispositions, using methods like endoscopic ultrasound and MRI. The American Gastroenterological Association and other organizations advise annual surveillance for high-risk individuals, typically starting at the age of 50 or 10 years younger than the youngest affected relative. For certain genetic syndromes, such as Peutz-Jeghers syndrome or hereditary pancreatitis, screening may begin as early as the age of 35 to 40 years.
Collapse
Affiliation(s)
- Ghada Mohamed
- Department of Internal Medicine, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA 01805, USA
| | - Malak Munir
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, ST, Suite 7705, Los Angeles, CA 90048, USA
| | - Amar Rai
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, ST, Suite 7705, Los Angeles, CA 90048, USA
| | - Srinivas Gaddam
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, ST, Suite 7705, Los Angeles, CA 90048, USA.
| |
Collapse
|
|
4
|
von Widdern JC, Rosendahl J, Ammer‐Herrmenau C. Chronic and Idiopathic Pancreatitis-A Personalized Treatment Approach. United European Gastroenterol J 2025; 13:116-124. [PMID: 39704081 PMCID: PMC11866313 DOI: 10.1002/ueg2.12741] [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: 07/02/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 12/21/2024] Open
Abstract
Chronic pancreatitis is a fibroinflammatory disease of the pancreas with heterogeneous clinical features and a significant socioeconomic burden. Assessing its aetiology and early diagnosis of associated complications remain challenging. Personalized therapy necessitates precise knowledge of the genetic, biological, and clinical differences within a patient population. In this context, the identification of the underlying aetiology represents an essential cornerstone. This review elucidates current standards for identifying underlying aetiologies and the diagnostic work-up for idiopathic cases. It provides an overview of general therapeutic approaches and highlights individual treatment options. Additionally, the follow-up management of pancreatitis-associated complications, namely exocrine pancreatic insufficiency, post-pancreatitis diabetes mellitus, pain management, pancreatic fluid collections, and pancreatic cancer risk, is summarized.
Collapse
Affiliation(s)
- Julian Cardinal von Widdern
- Department for Internal Medicine I (Gastroenterology, Pulmonology)University Hospital Halle (Saale)Halle (Saale)Germany
| | - Jonas Rosendahl
- Department for Internal Medicine I (Gastroenterology, Pulmonology)University Hospital Halle (Saale)Halle (Saale)Germany
| | - Christoph Ammer‐Herrmenau
- Department of GastroenterologyGastrointestinal Oncology and EndocrinologyUniversity Medical Center GoettingenGöttingenGermany
| |
Collapse
|
|
5
|
Fujiwara M. Diagnosis of Hereditary Pancreatitis Following the Initial Acute Episode With Multiple Pseudocyst Complications. Cureus 2024; 16:e73653. [PMID: 39677196 PMCID: PMC11645519 DOI: 10.7759/cureus.73653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2024] [Indexed: 12/17/2024] Open
Abstract
Hereditary pancreatitis (HP) is an unusual form of pancreatitis inherited as an autosomal dominant disorder. Patients typically present with recurrent acute pancreatitis-like symptoms that eventually progress to chronic pancreatitis, resulting in pancreatic exocrine insufficiency or diabetes mellitus, and a high risk of developing pancreatic cancer. As such, early diagnosis is crucial. Herein, we present the case of an 11-year-old boy with no significant medical history, but a family history of type 1 diabetes and pancreatic cancer, who presented with intermittent epigastric pain and nausea. Imaging revealed multiple pancreatic pseudocysts, pancreatic stones, and pancreatic duct dilation, resulting in the diagnosis of acute-on-chronic pancreatitis. Genetic testing confirmed the presence of a mutation in the PRSS1 gene, ultimately resulting in the diagnosis of HP. The patient remained symptom-free for five years during follow-up post-treatment. This case highlights the importance of considering HP in young patients presenting with pseudocysts and other signs of chronic pancreatitis even during the initial acute episode.
Collapse
Affiliation(s)
- Michimasa Fujiwara
- Pediatrics, National Hospital Organization Fukuyama Medical Center, Fukuyama, JPN
| |
Collapse
|
|
6
|
Kupnicka P, Król M, Żychowska J, Łagowski R, Prajwos E, Surówka A, Chlubek D. GLP-1 Receptor Agonists: A Promising Therapy for Modern Lifestyle Diseases with Unforeseen Challenges. Pharmaceuticals (Basel) 2024; 17:1470. [PMID: 39598383 PMCID: PMC11597758 DOI: 10.3390/ph17111470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 10/27/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
Modern lifestyle diseases remain a persistent challenge in healthcare. Currently, about 422 million people worldwide are affected by diabetes, while 1 in 8 people are living with obesity. The development of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has marked a significant milestone in treating these conditions. Interest in GLP-1RAs has grown due to evidence that, beyond their established role in diabetes management, these drugs influence other metabolic disorders. This is attributed to the fact that GLP-1 receptors are found in various healthy human tissues. However, a potential cause for concern is the expression of GLP-1 receptors in certain cancers. This review focuses on the most recent findings concerning the actions of GLP-1RAs, detailing their documented impact on the thyroid gland and pancreas. It addresses concerns about the long-term use of GLP-1RAs in relation to the development of pancreatitis, pancreatic cancer, and thyroid neoplasms by exploring the mechanisms and long-term effects in different patient subgroups and including data not discussed previously. This review was conducted through an examination of the literature available in the MedLine (PubMed) database, covering publications from 1978 to 10 May 2024. The collected articles were selected based on their relevance to studies of GLP-1 agonists and their effects on the pancreas and thyroid and assessed to meet the established inclusion criteria. The revised papers suggest that prolonged use of GLP-1RA could contribute to the formation of thyroid tumors and may increase the risk of acute inflammatory conditions such as pancreatitis, particularly in high-risk patients. Therefore, physicians should advise patients on the need for more frequent and detailed follow-ups.
Collapse
Affiliation(s)
- Patrycja Kupnicka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Małgorzata Król
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Justyna Żychowska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Ryszard Łagowski
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Eryk Prajwos
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| | - Anna Surówka
- Department of Plastic, Endocrine and General Surgery, Pomeranian Medical University, 72-010 Szczecin, Poland
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland
| |
Collapse
|
|
7
|
Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
| |
Collapse
|
|
8
|
Villaca CBP, Mastracci TL. Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function. Compr Physiol 2024; 14:5371-5387. [PMID: 39109973 PMCID: PMC11425433 DOI: 10.1002/cphy.c230008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology. Therefore, it is necessary to investigate how exocrine-endocrine "crosstalk" may impact pancreatic function. In this article, we discuss common exocrine diseases, including cystic fibrosis, acute, hereditary, and chronic pancreatitis, and the impact of these exocrine diseases on endocrine function. Additionally, we review how obesity and fatty pancreas influence exocrine function and the impact on cellular communication between the exocrine and endocrine compartments. Interestingly, in all pathologies, there is evidence that signals from the exocrine disease contribute to endocrine dysfunction and the progression to diabetes. Continued research efforts to identify the mechanisms that underlie the crosstalk between various cell types in the pancreas are critical to understanding normal pancreatic physiology as well as disease states. © 2024 American Physiological Society. Compr Physiol 14:5371-5387, 2024.
Collapse
Affiliation(s)
| | - Teresa L Mastracci
- Department of Biology, Indiana University Indianapolis, Indianapolis, Indiana, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, Indiana, USA
| |
Collapse
|
|
9
|
Yu B, Yu Y, Wang X, Xu C, Xiao Y. A narrative review on the role of genetics in children with acute recurrent pancreatitis and chronic pancreatitis. Pediatr Investig 2023; 7:268-276. [PMID: 38050536 PMCID: PMC10693666 DOI: 10.1002/ped4.12404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 09/27/2023] [Indexed: 12/06/2023] Open
Abstract
The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis.
Collapse
Affiliation(s)
- Bo Yu
- School of Clinical MedicineShanghai University of Medicine and Health SciencesShanghaiChina
| | - Yi Yu
- Pediatric DepartmentRuijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Xinqiong Wang
- Pediatric DepartmentRuijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
- Pediatric DepartmentRuijin Hospital NorthSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Chundi Xu
- Pediatric DepartmentRuijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
- Pediatric DepartmentRuijin Hospital NorthSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Yuan Xiao
- Pediatric DepartmentRuijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina
- Pediatric DepartmentXin Rui Hospital (Wuxi Branch of Ruijin Hospital)JiangsuChina
| |
Collapse
|
|
10
|
Masson E, Zou WB, Pu N, Rebours V, Génin E, Wu H, Lin JH, Wang YC, Abrantes A, Aguilera Munoz L, Albouys J, Alric L, Amiot X, Archambeaud I, Audiau S, Bastide L, Baudon J, Bellaiche G, Bellon S, Bertrand V, Bideau K, Billiemaz K, Billioud C, Bonnefoy S, Borderon C, Bournet B, Breton E, Brugel M, Buscail L, Cadiot G, Camus M, Causse X, Chamouard P, Chaput U, Cholet F, Ciocan DM, Clavel C, Coffin B, Coimet-Berger L, Creveaux I, Culetto A, Daboussi O, Mestier LDE, Degand T, D'Engremont C, Denis B, Dermine S, Desgrippes R, D'Aubigny AD, Enaud R, Fabre A, Gargot D, Gelsi E, Gentilcore E, Gincul R, Ginglinger-Favre E, Giovannini M, Gomercic C, Gondran H, Grainville T, Grandval P, Grasset D, Grimaldi S, Grimbert S, Hagege H, Heissat S, Hentic O, Herber-Mayne A, Hervouet M, Hoibian S, Jacques J, Jais B, Kaassis M, Koch S, Lacaze E, Lacroute J, Lamireau T, Laurent L, Guillou XLE, Rhun MLE, Leblanc S, Levy P, Lievre A, Lorenzo D, Maire F, Marcel K, Matias C, Mauillon J, Morgant S, Moussata D, Muller N, Nambot S, Napoleon B, Olivier A, Pagenault M, Pelletier AL, Pennec O, Pinard F, Pioche M, Prost B, et alMasson E, Zou WB, Pu N, Rebours V, Génin E, Wu H, Lin JH, Wang YC, Abrantes A, Aguilera Munoz L, Albouys J, Alric L, Amiot X, Archambeaud I, Audiau S, Bastide L, Baudon J, Bellaiche G, Bellon S, Bertrand V, Bideau K, Billiemaz K, Billioud C, Bonnefoy S, Borderon C, Bournet B, Breton E, Brugel M, Buscail L, Cadiot G, Camus M, Causse X, Chamouard P, Chaput U, Cholet F, Ciocan DM, Clavel C, Coffin B, Coimet-Berger L, Creveaux I, Culetto A, Daboussi O, Mestier LDE, Degand T, D'Engremont C, Denis B, Dermine S, Desgrippes R, D'Aubigny AD, Enaud R, Fabre A, Gargot D, Gelsi E, Gentilcore E, Gincul R, Ginglinger-Favre E, Giovannini M, Gomercic C, Gondran H, Grainville T, Grandval P, Grasset D, Grimaldi S, Grimbert S, Hagege H, Heissat S, Hentic O, Herber-Mayne A, Hervouet M, Hoibian S, Jacques J, Jais B, Kaassis M, Koch S, Lacaze E, Lacroute J, Lamireau T, Laurent L, Guillou XLE, Rhun MLE, Leblanc S, Levy P, Lievre A, Lorenzo D, Maire F, Marcel K, Matias C, Mauillon J, Morgant S, Moussata D, Muller N, Nambot S, Napoleon B, Olivier A, Pagenault M, Pelletier AL, Pennec O, Pinard F, Pioche M, Prost B, Queneherve L, Rebours V, Reboux N, Rekik S, Riachi G, Rohmer B, Roquelaure B, Hezode IR, Rostain F, Saurin JC, Servais L, Stan-Iuga R, Subtil C, Texier C, Thomassin L, Tougeron D, Tsakiris L, Valats JC, Vuitton L, Wallenhorst T, Wangerme M, Zanaldi H, Zerbib F. Classification of PRSS1 variants responsible for chronic pancreatitis: An expert perspective from the Franco-Chinese GREPAN study group. Pancreatology 2023; 23:491-506. [PMID: 37581535 DOI: 10.1016/j.pan.2023.04.004] [Show More Authors] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/06/2023] [Accepted: 04/13/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND PRSS1 was the first reported chronic pancreatitis (CP) gene. The existence of both gain-of-function (GoF) and gain-of-proteotoxicity (GoP) pathological PRSS1 variants, together with the fact that PRSS1 variants have been identified in CP subtypes spanning the range from monogenic to multifactorial, has made the classification of PRSS1 variants very challenging. METHODS All currently reported PRSS1 variants (derived primarily from two databases) were manually reviewed with respect to their clinical genetics, functional analysis and population allele frequency. They were classified by variant type and pathological mechanism within the framework of our recently proposed ACMG/AMP guidelines-based seven-category system. RESULTS The total number of distinct germline PRSS1 variants included for analysis was 100, comprising 3 copy number variants (CNVs), 12 5' and 3' variants, 19 intronic variants, 5 nonsense variants, 1 frameshift deletion variant, 6 synonymous variants, 1 in-frame duplication, 3 gene conversions and 50 missense variants. Based upon a combination of clinical genetic and functional analysis, population data and in silico analysis, we classified 26 variants (all 3 CNVs, the in-frame duplication, all 3 gene conversions and 19 missense) as "pathogenic", 3 variants (missense) as "likely pathogenic", 5 variants (four missense and one promoter) as "predisposing", 13 variants (all missense) as "unknown significance", 2 variants (missense) as "likely benign", and all remaining 51 variants as "benign". CONCLUSIONS We describe an expert classification of the 100 PRSS1 variants reported to date. The results have immediate implications for reclassifying many ClinVar-registered PRSS1 variants as well as providing optimal guidelines/standards for reporting PRSS1 variants.
Collapse
Affiliation(s)
- Emmanuelle Masson
- Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; Service de Génétique Médicale et de Biologie de la Reproduction, CHRU Brest, F-29200, Brest, France
| | - Wen-Bin Zou
- Department of Gastroenterology, Changhai Hospital, The Secondary Military Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Na Pu
- Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Vinciane Rebours
- Pancreatology and Digestive Oncology Department, Beaujon Hospital, APHP - Clichy, Université Paris Cité, Paris, France
| | - Emmanuelle Génin
- Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; Service de Génétique Médicale et de Biologie de la Reproduction, CHRU Brest, F-29200, Brest, France
| | - Hao Wu
- Department of Gastroenterology, Changhai Hospital, The Secondary Military Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Jin-Huan Lin
- Department of Gastroenterology, Changhai Hospital, The Secondary Military Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Yuan-Chen Wang
- Department of Gastroenterology, Changhai Hospital, The Secondary Military Medical University, Shanghai, China; Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Marc Hervouet
- Hôpital d'instruction des armées Percy, Clamart, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
11
|
Garutti M, Foffano L, Mazzeo R, Michelotti A, Da Ros L, Viel A, Miolo G, Zambelli A, Puglisi F. Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool. Genes (Basel) 2023; 14:1025. [PMID: 37239385 PMCID: PMC10218093 DOI: 10.3390/genes14051025] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could be challenging because of a lack of validated testing criteria or because of their suboptimal performance. In addition, many clinicians are not sufficiently well trained to identify and select patients that could benefit from a genetic test. Herein, we searched the available literature to comprehensively review and categorize hereditary cancer syndromes affecting adults with the aim of helping clinicians in their daily clinical practice through a visual tool.
Collapse
Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Lorenzo Foffano
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Roberta Mazzeo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Anna Michelotti
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Lucia Da Ros
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alessandra Viel
- Unit of Oncogenetics and Genomics CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Gianmaria Miolo
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Alberto Zambelli
- Medical Oncology and Hematology Unit, IRCCS—Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy
- Department of Medicine, University of Udine, 33100 Udine, Italy
| |
Collapse
|
|
12
|
van Wilpe R, Hulst AH, Siegelaar SE, DeVries JH, Preckel B, Hermanides J. Type 1 and other types of diabetes mellitus in the perioperative period. What the anaesthetist should know. J Clin Anesth 2023; 84:111012. [PMID: 36427486 DOI: 10.1016/j.jclinane.2022.111012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 10/31/2022] [Accepted: 11/15/2022] [Indexed: 11/23/2022]
Abstract
Diabetes mellitus is often treated as a uniform disease in the perioperative period. Type 2 diabetes is most commonly encountered, and only a minority of surgical patients have been diagnosed with another type of diabetes. Patients with a specific type of diabetes can be particularly prone to perioperative glycaemic dysregulation. In addition, certain type-related features and pitfalls should be taken into account in the operating theatre. In this narrative review, we discuss characteristics of types of diabetes other than type 2 diabetes relevant to the anaesthetist, based on available literature and data from our clinic.
Collapse
Affiliation(s)
- Robert van Wilpe
- Department of Anaesthesiology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands
| | - Abraham H Hulst
- Department of Anaesthesiology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands
| | - Sarah E Siegelaar
- Department of Endocrinology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands
| | - J Hans DeVries
- Department of Endocrinology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands
| | - Benedikt Preckel
- Department of Anaesthesiology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands.
| | - Jeroen Hermanides
- Department of Anaesthesiology, Amsterdam UMC location AMC, University of Amsterdam, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, the Netherlands
| |
Collapse
|
|
13
|
Pancreatic Cancer in Chronic Pancreatitis: Pathogenesis and Diagnostic Approach. Cancers (Basel) 2023; 15:cancers15030761. [PMID: 36765725 PMCID: PMC9913572 DOI: 10.3390/cancers15030761] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/20/2023] [Accepted: 01/24/2023] [Indexed: 01/28/2023] Open
Abstract
Chronic pancreatitis is one of the main risk factors for pancreatic cancer, but it is a rare event. Inflammation and oncogenes work hand in hand as key promoters of this disease. Tobacco is another co-factor. During alcoholic chronic pancreatitis, the cumulative risk of cancer is estimated at 4% after 15 to 20 years. This cumulative risk is higher in hereditary pancreatitis: 19 and 12% in the case of PRSS1 and SPINK1 mutations, respectively, at an age of 60 years. The diagnosis is difficult due to: (i) clinical symptoms of cancer shared with those of chronic pancreatitis; (ii) the parenchymal and ductal remodeling of chronic pancreatitis rendering imaging analysis difficult; and (iii) differential diagnoses, such as pseudo-tumorous chronic pancreatitis and paraduodenal pancreatitis. Nevertheless, the occurrence of cancer during chronic pancreatitis must be suspected in the case of back pain, weight loss, unbalanced diabetes, and jaundice, despite alcohol withdrawal. Imaging must be systematically reviewed. Endoscopic ultrasound-guided fine-needle biopsy can contribute by targeting suspicious tissue areas with the help of molecular biology (search for KRAS, TP53, CDKN2A, DPC4 mutations). Short-term follow-up of patients is necessary at the clinical and paraclinical levels to try to diagnose cancer at a surgically curable stage. Pancreatic surgery is sometimes necessary if there is any doubt.
Collapse
|
|
14
|
Greeley SAW, Polak M, Njølstad PR, Barbetti F, Williams R, Castano L, Raile K, Chi DV, Habeb A, Hattersley AT, Codner E. ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2022; 23:1188-1211. [PMID: 36537518 PMCID: PMC10107883 DOI: 10.1111/pedi.13426] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 09/30/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Siri Atma W. Greeley
- Section of Pediatric and Adult Endocrinology, Diabetes and Metabolism, Kovler Diabetes Center and Comer Children's HospitalUniversity of Chicago MedicineChicagoIllinoisUSA
| | - Michel Polak
- Hôpital Universitaire Necker‐Enfants MaladesUniversité de Paris Cité, INSERM U1016, Institut IMAGINEParisFrance
| | - Pål R. Njølstad
- Department of Clinical ScienceUniversity of Bergen, and Children and Youth Clinic, Hauk eland University HospitalBergenNorway
| | - Fabrizio Barbetti
- Clinical Laboratory UnitBambino Gesù Children's Hospital, IRCCSRomeItaly
| | - Rachel Williams
- National Severe Insulin Resistance ServiceCambridge University Hospitals NHS TrustCambridgeUK
| | - Luis Castano
- Endocrinology and Diabetes Research Group, Biocruces Bizkaia Health Research InstituteCruces University Hospital, CIBERDEM, CIBERER, Endo‐ERN, UPV/EHUBarakaldoSpain
| | - Klemens Raile
- Department of Paediatric Endocrinology and DiabetologyCharité – UniversitätsmedizinBerlinGermany
| | - Dung Vu Chi
- Center for Endocrinology, Metabolism, Genetics and Molecular Therapy, Departement of Pediatric Endocrinology and DiabetesVietnam National Children's HospitalHanoiVietnam
- Department of Pediatrics and Department of Biology and Medical GeneticsHanoi Medical UniversityHanoiVietnam
| | - Abdelhadi Habeb
- Department of PediatricsPrince Mohamed bin Abdulaziz Hopsital, National Guard Health AffairsMadinahSaudi Arabia
| | - Andrew T. Hattersley
- Institute of Biomedical and Clinical SciencesUniversity of Exeter Medical SchoolExeterUK
| | - Ethel Codner
- Institute of Maternal and Child ResearchSchool of Medicine, University of ChileSantiagoChile
| |
Collapse
|
|
15
|
Samuel SM, Varghese E, Kubatka P, Büsselberg D. Tirzepatide-Friend or Foe in Diabetic Cancer Patients? Biomolecules 2022; 12:1580. [PMID: 36358930 PMCID: PMC9687454 DOI: 10.3390/biom12111580] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/12/2022] [Accepted: 10/25/2022] [Indexed: 09/25/2023] Open
Abstract
It is a well-accepted fact that obesity and diabetes increase the risk of incidence of different cancers and their progression, leading to a decrease in the quality of life among affected cancer patients. In addition to decreasing the risk of cancers, maintaining a healthy body mass index (BMI)/body weight and/or blood glucose levels within the normal range critically impacts the response to anti-cancer therapy among affected individuals. A cancer patient managing their body weight and maintaining blood glucose control responds better to anti-cancer therapy than obese individuals and those whose blood glucose levels remain higher than normal during therapeutic intervention. In some cases, anti-diabetic/glucose-lowering drugs, some of which are also used to promote weight loss, were found to possess anti-cancer potential themselves and/or support anti-cancer therapy when used to treat such patients. On the other hand, certain glucose-lowering drugs promoted the cancer phenotype and risked cancer progression when used for treatment. Tirzepatide (TRZD), the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) agonist, has recently gained interest as a promising injectable drug for the treatment of type 2 diabetes and was approved by the FDA after successful clinical trials (SURPASS 1/2/3/4 and 5, NCT03954834, NCT03987919, NCT03882970, NCT03730662, and NCT04039503). In addition, the reports from the SURMOUNT-1 clinical trial (NCT04184622) support the use of TRZD as an anti-obesity drug. In the current review article, we examine the possibility and molecular mechanisms of how TRZD intervention could benefit cancer therapeutics or increase the risk of cancer progression when used as an anti-diabetic drug in diabetic patients.
Collapse
Affiliation(s)
- Samson Mathews Samuel
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar
| | - Elizabeth Varghese
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar
| |
Collapse
|
|
16
|
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
|
|
17
|
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
|
|
18
|
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
|
|
19
|
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: 6] [Impact Index Per Article: 2.0] [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
|
|
20
|
Losurdo G, Gravina AG, Maroni L, Gabrieletto EM, Ianiro G, Ferrarese A. Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective. Dig Liver Dis 2022; 54:583-597. [PMID: 34509394 DOI: 10.1016/j.dld.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.
Collapse
Affiliation(s)
- Giuseppe Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari; PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari.
| | - Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Maroni
- Department of Gastroenterology, Marche Polytechnic University, Ancona, Italy
| | | | - Gianluca Ianiro
- Digestive Disease Center, Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Alberto Ferrarese
- Gastroenterology and Hepatology, Azienda Ospedaliera Universitaria Integrata, Ospedale Borgo Trento, Verona, Italy
| |
Collapse
|
|
21
|
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
|
|
22
|
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
|
|
23
|
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
|
|
24
|
Mehta V, Hopson PE, Smadi Y, Patel SB, Horvath K, Mehta DI. Development of the human pancreas and its exocrine function. Front Pediatr 2022; 10:909648. [PMID: 36245741 PMCID: PMC9557127 DOI: 10.3389/fped.2022.909648] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 08/11/2022] [Indexed: 11/25/2022] Open
Abstract
The pancreas has both endocrine and exocrine function and plays an important role in digestion and glucose control. Understanding the development of the pancreas, grossly and microscopically, and the genetic factors regulating it provides further insight into clinical problems that arise when these processes fail. Animal models of development are known to have inherent issues when understanding human development. Therefore, in this review, we focus on human studies that have reported gross and microscopic development including acinar-, ductal-, and endocrine cells and the neural network. We review the genes and transcription factors involved in organ formation using data from animal models to bridge current understanding where necessary. We describe the development of exocrine function in the fetus and postnatally. A deeper review of the genes involved in pancreatic formation allows us to describe the development of the different groups (proteases, lipids, and amylase) of enzymes during fetal life and postnatally and describe the genetic defects. We discuss the constellation of gross anatomical, as well as microscopic defects that with genetic mutations lead to pancreatic insufficiency and disease states.
Collapse
Affiliation(s)
- Vijay Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Puanani E Hopson
- Department of Children Center, Pediatric and Adolescent Medicine, Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Yamen Smadi
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Samit B Patel
- Pediatric Gastroenterology and Nutrition of Tampa Bay, Tampa Bay, FL, United States
| | - Karoly Horvath
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| | - Devendra I Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, FL, United States
| |
Collapse
|
|
25
|
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
|
|
26
|
Saad M, Vitale DS. Endoscopic Advancements in Pediatric Pancreatitis. Front Pediatr 2022; 10:937136. [PMID: 35783303 PMCID: PMC9240213 DOI: 10.3389/fped.2022.937136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 05/27/2022] [Indexed: 11/22/2022] Open
Affiliation(s)
- Michelle Saad
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
| | - David S Vitale
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| |
Collapse
|
|
27
|
Inherited pancreatic exocrine insufficiency and pancreatitis: When children transition to adult care. Best Pract Res Clin Gastroenterol 2021; 56-57:101782. [PMID: 35331395 DOI: 10.1016/j.bpg.2021.101782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/09/2021] [Accepted: 12/07/2021] [Indexed: 01/31/2023]
Abstract
Hereditary pancreatitis (HP) encompasses two distinct disease groups: the first manifests as congenital exocrine pancreatic insufficiency (EPI), and the second includes hereditary forms of pancreatitis. EPI represents the ultimate expression of gland function loss. Cystic fibrosis is by far the most frequent aetiology of early-onset EPI; genetics and a growing understanding of the disease mechanisms have paved the way for innovative and personalized treatment approaches. Efforts are ongoing to further decipher the pathophysiology and explore new therapies for other causes of EPI. HP occurs in patients carrying mutations in genes encoding digestive proteases or proteins playing an important role in proper pancreatic function and homeostasis. Improved sequencing techniques have led to the discovery of several causal and disease promoting genes. Most forms of HP have a paediatric onset but complications usually manifest during adulthood. Surveillance in experienced centres is mandatory to diagnose and address these complications in a timely manner.
Collapse
|
|
28
|
Xu F, Yang C, Tang M, Wang M, Cheng Z, Chen D, Chen X, Liu K. The Role of Gut Microbiota and Genetic Susceptibility in the Pathogenesis of Pancreatitis. Gut Liver 2021; 16:686-696. [PMID: 34911043 PMCID: PMC9474482 DOI: 10.5009/gnl210362] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/06/2021] [Accepted: 09/17/2021] [Indexed: 11/22/2022] Open
Abstract
Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.
Collapse
Affiliation(s)
- Fumin Xu
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Chunmei Yang
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Mingcheng Tang
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Ming Wang
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Zhenhao Cheng
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Dongfeng Chen
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Xiao Chen
- Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China
| | - Kaijun Liu
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| |
Collapse
|
|
29
|
Cowan RW, Pratt ED, Kang JM, Zhao J, Wilhelm JJ, Abdulla M, Qiao EM, Brennan LP, Ulintz PJ, Bellin MD, Rhim AD. Pancreatic Cancer-Related Mutational Burden Is Not Increased in a Patient Cohort With Clinically Severe Chronic Pancreatitis. Clin Transl Gastroenterol 2021; 12:e00431. [PMID: 34797250 PMCID: PMC8604013 DOI: 10.14309/ctg.0000000000000431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/30/2021] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Chronic pancreatitis is associated with an increased risk of developing pancreatic cancer, and patients with inherited forms of pancreatitis are at greatest risk. We investigated whether clinical severity of pancreatitis could also be an indicator of cancer risk independent of etiology by performing targeted DNA sequencing to assess the mutational burden in 55 cancer-associated genes. METHODS Using picodroplet digital polymerase chain reaction and next-generation sequencing, we reported the genomic profiles of pancreases from severe clinical cases of chronic pancreatitis that necessitated palliative total pancreatectomy with islet autotransplantation. RESULTS We assessed 57 tissue samples from 39 patients with genetic and idiopathic etiologies and found that despite the clinical severity of disease, there was no corresponding increase in mutational burden. The average allele frequency of somatic variants was 1.19% (range 1.00%-5.97%), and distinct regions from the same patient displayed genomic heterogeneity, suggesting that these variants are subclonal. Few oncogenic KRAS mutations were discovered (7% of all samples), although we detected evidence of frequent cancer-related variants in other genes such as TP53, CDKN2A, and SMAD4. Of note, tissue samples with oncogenic KRAS mutations and samples from patients with PRSS1 mutations harbored an increased total number of somatic variants, suggesting that these patients may have increased genomic instability and could be at an increased risk of developing pancreatic cancer. DISCUSSION Overall, we showed that even in those patients with chronic pancreatitis severe enough to warrant total pancreatectomy with islet autotransplantation, pancreatic cancer-related mutational burden is not appreciably increased.
Collapse
Affiliation(s)
- Robert W. Cowan
- Ahmed Cancer Center for Pancreatic Cancer Research, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
- Department of Gastroenterology, Hepatology & Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
| | - Erica D. Pratt
- Ahmed Cancer Center for Pancreatic Cancer Research, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
- Department of Gastroenterology, Hepatology & Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
| | - Jin Muk Kang
- Ahmed Cancer Center for Pancreatic Cancer Research, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
- Department of Gastroenterology, Hepatology & Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
| | - Jun Zhao
- Ahmed Cancer Center for Pancreatic Cancer Research, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
- Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA
| | - Joshua J. Wilhelm
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA;
- Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, Minnesota, USA;
| | - Muhamad Abdulla
- Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, Minnesota, USA;
| | - Edmund M. Qiao
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA;
| | - Luke P. Brennan
- University of Michigan Medical School, Ann Arbor, Michigan, USA;
| | - Peter J. Ulintz
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA;
- BRCF Bioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA.
| | - Melena D. Bellin
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA;
- Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, Minnesota, USA;
| | - Andrew D. Rhim
- Ahmed Cancer Center for Pancreatic Cancer Research, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
- Department of Gastroenterology, Hepatology & Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA;
| |
Collapse
|
|
30
|
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
|
|
31
|
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
|
|
32
|
Genetic Risk Factors in Early-Onset Nonalcoholic Chronic Pancreatitis: An Update. Genes (Basel) 2021; 12:genes12050785. [PMID: 34065437 PMCID: PMC8160726 DOI: 10.3390/genes12050785] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/15/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic pancreatitis (CP) is a progressive, irreversible inflammatory disorder of the pancreas, which results from interrelations between different genetic and environmental factors. Genetic variants are the primary cause of the disease in early-onset nonalcoholic CP patients. Novel CP-associated genes are continuously emerging from genetic studies on CP cohorts, providing important clues for distinct mechanisms involved in CP development. On the basis of functional studies, the genetic alterations have been sub-grouped into CP-driving pathological pathways. This review focuses on the concept of CP as a complex disease driven by multiple genetic factors. We will discuss only well-defined genetic risk factors and distinct functional pathways involved in CP development, especially in the context of the early-onset nonalcoholic CP group. The diagnostic implications of the genetic testing will be addressed as well.
Collapse
|
|
33
|
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
|
|
34
|
Andersson R, Löhr JM. Swedish national guidelines for chronic pancreatitis. Scand J Gastroenterol 2021; 56:469-483. [PMID: 33617407 DOI: 10.1080/00365521.2021.1881815] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/11/2021] [Accepted: 01/20/2021] [Indexed: 02/04/2023]
Abstract
Chronic pancreatitis (CP) should be suspected in the case of recurrent upper abdominal pain of unknown origin and/or clinical signs of exocrine pancreatic insufficiency (EPI). Alcohol is the most common etiological factor associated with CP, others being smoking, male gender, and hereditary forms. CP is often associated with recurrent episodes of acute exacerbations.As of today, there is no accepted clinical definition of CP. However, irreversible morphological changes within the pancreas often occur, including dilatation of the main and branch pancreatic ducts, calcifications in ducts and parenchyma, parenchymal atrophy, and development of pseudocysts, though less so in the early phase of CP.
Collapse
|
|
35
|
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
|
|
36
|
Jones TE, Bellin MD, Yadav D, Freeman ML, Schwarzenberg SJ, Slivka A, Chennat JS, Beilman GJ, Chinnakotla S, Pruett TL, Kirchner V, Humar A, Wijkstrom M, Zureikat AH, Nikiforova MN, Wald AI, Whitcomb DC, Singhi AD. The histopathology of SPINK1-associated chronic pancreatitis. Pancreatology 2020; 20:1648-1655. [PMID: 33097431 PMCID: PMC7704661 DOI: 10.1016/j.pan.2020.10.030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 09/20/2020] [Accepted: 10/08/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The identification of genetic risk factors for chronic pancreatitis, such as PRSS1, CFTR and SPINK1, provides the opportunity to define key pathologic hallmarks and etiologic-specific changes. For example, pancreata from PRSS1 and CFTR patients exhibit progressive lipomatous atrophy without significant fibrosis. Considering the pathology of SPINK1-associated pancreatitis is ill-defined, we examined the pancreata of SPINK1 patients with chronic pancreatitis. METHODS Histologic sections after total pancreatectomy with islet autotransplantation and associated clinicopathologic data were collected from 28 patients with SPINK1 germline alterations. Clinical findings, germline data, anatomic anomalies and pathologic findings were descriptively evaluated. RESULTS Patients ranged in age from 5 to 48 years (median, 21.6 years) with abdominal pain between 2 and 25 years (median, 5.8 years). Most patients were SPINK1 heterozygous and 14 (50%) had co-occurring CFTR (n = 12) and CTRC (n = 2) mutations. Other pancreatitis risk factors included anatomic anomalies (n = 9) and tobacco use (n = 1). Overall, 24 (86%) patients had additional pancreatitis-associated germline alterations, SPINK1 homozygosity, anatomic anomalies or environmental factors. Examination of pancreata revealed a sequential pattern of exocrine parenchymal loss and replacement by prominent fibrosis, dependent on the duration of abdominal pain. No malignancies were identified, but low-grade pancreatic intraepithelial neoplasia was present for 2 cases. CONCLUSIONS Within this descriptive study, SPINK1-associated pancreatitis is characterized by parenchymal fibrosis and suggests divergent pathophysiologic mechanisms from PRSS1 and CFTR-associated pancreatitis. Moreover, SPINK1 patients frequently had additional etiologic factors that did not impact the development of pancreatic fibrosis and may implicate SPINK1 as a disease modifier gene.
Collapse
Affiliation(s)
- Terrell E Jones
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melena D Bellin
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Dhiraj Yadav
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Martin L Freeman
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Sarah J Schwarzenberg
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Adam Slivka
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Jennifer S Chennat
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Gregory J Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Srinath Chinnakotla
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Timothy L Pruett
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Varvara Kirchner
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Abhinav Humar
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Martin Wijkstrom
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Marina N Nikiforova
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Abigail I Wald
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David C Whitcomb
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| |
Collapse
|
|
37
|
Greenhalf W, Lévy P, Gress T, Rebours V, Brand RE, Pandol S, Chari S, Jørgensen MT, Mayerle J, Lerch MM, Hegyi P, Kleeff J, Castillo CFD, Isaji S, Shimosegawa T, Sheel A, Halloran CM, Garg P, Takaori K, Besselink MG, Forsmark CE, Wilcox CM, Maisonneuve P, Yadav D, Whitcomb D, Neoptolemos J. International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 2020; 20:910-918. [PMID: 32624419 DOI: 10.1016/j.pan.2020.05.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 05/14/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. METHODS The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. CONCLUSIONS Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation.
Collapse
Affiliation(s)
- William Greenhalf
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Philippe Lévy
- Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l'Appareil Digestif, DHU UNITY, Hôpital Beaujon, APHP, 92118 Clichy Cedex, and Université Paris 7, France
| | - Thomas Gress
- Department of Gastroenterology, Endocrinology and Metabolism, University Hospital, Philipps-Universität Marburg, Marburg, Germany
| | - Vinciane Rebours
- Service de Pancréatologie-Gastroentérologie, Pôle des Maladies de l'Appareil Digestif, DHU UNITY, Hôpital Beaujon, APHP, 92118 Clichy Cedex, and Université Paris 7, France
| | - Randall E Brand
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Pittsburgh Medical Center, 5200 Centre Avenue, Suite 409, Pittsburgh, PA, 15232, USA
| | - Steve Pandol
- Cedars-Sinai Medical Center, Los Angeles, CA, United States Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine, University of California, Los Angeles, CA, USA
| | - Suresh Chari
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Julia Mayerle
- Department of Medicine II, University Hospital, LMU, Munich, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, D-17475, Greifswald, Germany
| | - Péter Hegyi
- Institute for Translational Medicine &Department of Translational Medicine/1st Department of Medicine, Medical School, Pécs, H-7624, Hungary
| | - Jörg Kleeff
- Department of Surgery, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany
| | | | - Shuiji Isaji
- Department of Surgery, Mie University Graduate School of Medicine, Japan.
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Andrea Sheel
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Christopher M Halloran
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Pramod Garg
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Kyoichi Takaori
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Marc G Besselink
- Department of Surgery, Amsterdam Gastroenterology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Chris E Forsmark
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA
| | | | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy.
| | - Dhiraj Yadav
- Department of Medicine University of Pittsburgh and UPMC, Pittsburgh, PA, USA
| | - David Whitcomb
- Department of Medicine University of Pittsburgh and UPMC, Pittsburgh, PA, USA
| | - John Neoptolemos
- Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
| |
Collapse
|
|
38
|
Zhang JY, Deng ZH, Gong B. Pancreaticopleural fistula in children with chronic pancreatitis: a case report and literature review. BMC Pediatr 2020; 20:274. [PMID: 32493299 PMCID: PMC7268358 DOI: 10.1186/s12887-020-02174-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/27/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Pancreaticopleural fistula (PPF) is a very rare and critical complication of pancreatitis in children. The majority of publications relevant to PPF are case reports. No pooled analyses of PPF cases are available. Little is known about the pathogenesis and optimal therapeutic schedule. The purpose of this study was to identify the pathogenesis and optimal therapeutic schedule of PPF in children. CASE PRESENTATION The patient was a 13-year-old girl who suffered from intermittent chest tightness and dyspnea for more than 3 months; she was found to have chronic pancreatitis complicated by PPF. The genetic screening revealed SPINK1 mutation. She was treated with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic retrograde pancreatic drainage (ERPD); her symptoms improved dramatically after the procedures. CONCLUSIONS PPF is a rare pancreatic complication in children and causes significant pulmonary symptoms that can be misdiagnosed frequently. PPF in children is mainly associated with chronic pancreatitis (CP); therefore, we highlight the importance of genetic testing. Endoscopic treatment is recommended when conservative treatment is ineffective.
Collapse
Affiliation(s)
- Jia-Yu Zhang
- Department of Pediatric Digestive Diseases, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Zhao-Hui Deng
- Department of Pediatric Digestive Diseases, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Biao Gong
- Department of Digestive Diseases, Shanghai Shuguang Hospital, Shanghai University of Chinese Medicine, Shanghai, 201203, China.
| |
Collapse
|
|
39
|
Asai A, Konno M, Kawamoto K, Isotani A, Mori M, Eguchi H, Doki Y, Arai T, Ishii H. Hereditary pancreatitis model by blastocyst complementation in mouse. Oncotarget 2020; 11:2061-2073. [PMID: 32547704 PMCID: PMC7275788 DOI: 10.18632/oncotarget.27595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 04/03/2020] [Indexed: 12/15/2022] Open
Abstract
The application of pluripotent stem cells is expected to contribute to the elucidation of unknown mechanism of human diseases. However, in vitro induction of organ-specific cells, such as pancreas and liver, is still difficult and the reproduction of their disorders in a model has been unfeasible. To study the mechanism of human hereditary pancreatitis (HP), we here performed the blastocyst complementation (BC) method. In the BC method, mouse embryonic stem (ES) cells harboring CRISPR/CAS9-mediated mutations in the Prss1 gene were injected into blastocysts with deficient Pdx1 gene, which is a critical transcription factor in the development of pancreas. The results showed that trypsin was activated extremely in Prss1-mutant mice. This implied that the mouse phenotype mimics that of human HP and that the BC method was useful for the reproduction and study of pancreatic disorders. The present study opens the possibility of investigating uncharacterized human diseases by utilizing the BC method.
Collapse
Affiliation(s)
- Ayumu Asai
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Medical Data Science, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| | - Masamitsu Konno
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Medical Data Science, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| | - Koichi Kawamoto
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| | - Ayako Isotani
- Organ Developmental Engineering, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192 Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| | | | - Hideshi Ishii
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan.,Department of Medical Data Science, Graduate School of Medicine, Osaka University, Suita 565-0871 Japan
| |
Collapse
|
|
40
|
Pagliari D, Ainora ME, Brizi MG, Cintoni M, Rinninella E, Attili F, Mancarella FA, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Manfredi R, Zocco MA. A new ultrasound score for the assessment and follow-up of chronic pancreatitis: The 'Gemelli USCP score'. Dig Liver Dis 2020; 52:644-650. [PMID: 32273171 DOI: 10.1016/j.dld.2020.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 01/31/2020] [Accepted: 03/04/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Ultrasound (US) is frequently the first line imaging technique used in patients with abdominal pain and clinical suspicion of chronic pancreatitis (CP), but its role in the diagnosis and follow-up of CP is still controversial. AIMS We aimed to develop a dedicated score for the US staging of CP and to evaluate the agreement of this score with standard imaging techniques. METHODS Ninety consecutive patients with a diagnosis of CP referred to the pancreatic outpatient clinic of A. Gemelli Hospital between June and September 2018 were recruited in the study. Patients underwent pancreatic US to evaluate different morphological parameters to develop an US based score system, called the Gemelli UltraSound Chronic Pancreatitis (USCP) score. RESULTS The Gemelli USCP score significantly increased according to the Cambridge score for both mean value (p<0.0001) and each parameter evaluated (p<0.0001). Moreover, we found a significant correlation between the score and laboratory parameters related to pancreatic exocrine insufficiency such as vitamin D, B9, and B12 deficiency and fecal elastase values (p<0.0001). CONCLUSIONS The development of a dedicated US score could be useful in the follow up of patients with CP as alternative non-invasive technique to standard radiological imaging.
Collapse
Affiliation(s)
- Danilo Pagliari
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy; Pancreatic Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy.
| | - Maria Elena Ainora
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Maria Gabriella Brizi
- Department of Radiology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Marco Cintoni
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Emanuele Rinninella
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Fabia Attili
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Francesco A Mancarella
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Matteo Garcovich
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Laura Riccardi
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Maurizio Pompili
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Riccardo Manfredi
- Department of Radiology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| | - Maria Assunta Zocco
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Catholic University of the Sacred Heart, Rome, Italy
| |
Collapse
|
|
41
|
O'Brien CM, O'Brien AC, Gleeson L, Conlon K, Feeney J, Malone DE. Imaging of genetically-mediated pancreatitis. Clin Imaging 2020; 65:113-118. [PMID: 32387800 DOI: 10.1016/j.clinimag.2020.04.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 03/12/2020] [Accepted: 04/07/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To review the imaging of patients with Genetically-Mediated Pancreatitis (GMP), identify common imaging findings in this cohort and assess phenotypical characteristics of specific genotypes. MATERIALS AND METHODS Retrospective review of the databases of the Irish National Surgical Centre for Pancreatic Cancer (NSCPC) and Cystic Fibrosis (CF) from November 2010 to January 2018. Retrospective imaging and chart review for the patients with positive genetics for GMP. RESULTS The NSCPC database contained 699 patients; the CF database included 352 patients. Of these 1051, 14 were identified as having GMP (age range: 20-65, M:F ratio of 1:1). 14 of 1051 patients from the database had positive genetics for GMP. 10 had imaging to support a diagnosis of hereditary pancreatitis or familial recurrent pancreatitis (1.3%) and 4 had imaging to support a diagnosis of CF-related pancreatitis. Imaging findings were considered in 3 categories, determined by genotype - PRSS1 hereditary pancreatitis, SPINK 1 autosomal recessive pancreatitis and those for CFTR - cystic fibrosis related pancreatitis. Imaging findings in PRSS1 hereditary pancreatitis patients included: pancreatic atrophy, calcification and main pancreatic duct (MPD) dilatation, referred to as the PRSS1 imaging triad. Patients with the SPINK1 gene mutation had less severe imaging manifestations (pancreatic atrophy 33%, MPD dilatation 33%, pancreatic calcification 33%). CFTR patients with imaging findings had pancreatic atrophy (100%). CONCLUSION GMP should be suspected when the features of 'chronic pancreatitis' are seen in young adults with no history of excess alcohol intake. Genetic testing, endocrinology review and long-term imaging follow-up for pancreatic carcinoma are indicated.
Collapse
Affiliation(s)
- Ciara M O'Brien
- St. Vincent's University Hospital, 196 Merrion Rd, Elm Park, Dublin, D04T6F4, Ireland.
| | - Amy C O'Brien
- St. Vincent's University Hospital, 196 Merrion Rd, Elm Park, Dublin, D04T6F4, Ireland.
| | - Laura Gleeson
- St. Vincent's University Hospital, 196 Merrion Rd, Elm Park, Dublin, D04T6F4, Ireland.
| | - Kevin Conlon
- St. Vincent's University Hospital, 196 Merrion Rd, Elm Park, Dublin, D04T6F4, Ireland; Tallaght University Hospital, Tallaght, Dublin D24 NR0A, Ireland.
| | - John Feeney
- Tallaght University Hospital, Tallaght, Dublin D24 NR0A, Ireland.
| | - Dermot E Malone
- St. Vincent's University Hospital, 196 Merrion Rd, Elm Park, Dublin, D04T6F4, Ireland.
| |
Collapse
|
|
42
|
Chou CY, Chang CT, Chen CJ. Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2020; 34 Suppl 1:e8580. [PMID: 31502717 DOI: 10.1002/rcm.8580] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/28/2019] [Accepted: 09/03/2019] [Indexed: 06/10/2023]
Abstract
RATIONALE Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis and pancreatic cancer (PC) is one of the most lethal types of cancer that is symptomless in the early stage. Because the clinical and image findings of CP can overlap that of pancreatic cancer (PC) which leads to confusion in the diagnosis and treatment of PC, discovery/verification/validation of more accurate protein biomarkers to diagnose CP and PC is in urgent need. METHODS The PubMed, Web of Science, and Google Scholar were searched using the keywords: 'biomarker', 'marker', 'chronic pancreatitis', "pancreatic cancer" or "proteomics" for highly related researches. We focused on the articles published after the year 2005 in this review. RESULTS We introduce the background to CP and PC and summarize the diagnosis of CP and PC, analytically validated protein biomarkers, and proteomic approaches for discovery/verification/validation. The potential use of mass spectrometry (MS) in clinical diagnosis is also discussed. CONCLUSIONS Continuously improving sensitivity of MS can provide deeper proteome for new marker discovery and high reliability for protein marker verification, validation, and clinical diagnosis. The analytically validated protein markers could be considered as targeted protein biomarkers for developing a MS platform in the clinical validation process or clinical diagnosis of CP and PC.
Collapse
Affiliation(s)
- Che-Yi Chou
- Division of Nephrology, Asia University Hospital, Taichung, Taiwan
- Department of Post-baccalaureate Veterinary Medicine, Asia University, Taichung, Taiwan
| | - Chiz-Tzung Chang
- College of Medicine, China Medical University, Taichung, Taiwan
- Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40447, Taiwan
| | - Chao-Jung Chen
- Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, 40402, Taiwan
| |
Collapse
|
|
43
|
Sirtl S, Oehrle B, Mayerle J, Goni E. [Diabetes and pancreatic cancer - state of the art]. MMW Fortschr Med 2020; 162:42-46. [PMID: 32342372 DOI: 10.1007/s15006-020-0428-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Affiliation(s)
- Simon Sirtl
- Medizinische Klinik und Poliklinik II, Klinikum der Ludwig-Maximilians, Universität München, Deutschland
| | - Bettina Oehrle
- Medizinische Klinik und Poliklinik II, Klinikum der Ludwig-Maximilians, Universität München, Deutschland
| | - Julia Mayerle
- Medizinische Klinik und Poliklinik II, Klinikum der Ludwig-Maximilians-Universität München Campus Großhadern, Marchioninistr. 15, D-81377, München, Deutschland.
| | - Elisabetta Goni
- Medizinische Klinik und Poliklinik II, Klinikum der Ludwig-Maximilians, Universität München, Deutschland
| |
Collapse
|
|
44
|
Agarwal S, Sharma S, Gunjan D, Singh N, Kaushal K, Poudel S, Anand A, Gopi S, Mohta S, Sonika U, Saraya A. Natural course of chronic pancreatitis and predictors of its progression. Pancreatology 2020; 20:347-355. [PMID: 32107194 DOI: 10.1016/j.pan.2020.02.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/26/2020] [Accepted: 02/06/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP. METHODS This study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model. RESULTS A total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5-7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4-2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34-0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66-1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03-1.7); p = 0.028] and diabetes[HR:2.7(2.2-3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7-31.2); p < 0.001], smoking-history[HR:6.5(2.2-19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05-0.4); p < 0.001]. CONCLUSION ACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.
Collapse
Affiliation(s)
- Samagra Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Kanav Kaushal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Shekhar Poudel
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Srikant Gopi
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Srikant Mohta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ujjwal Sonika
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India.
| |
Collapse
|
|
45
|
Abstract
PURPOSE OF REVIEW The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features. RECENT FINDINGS Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.
Collapse
Affiliation(s)
- Gabriel Xavier Ramalho
- School of Medicine, Faculty of Education and Health Sciences, University Center of Brasilia (UniCEUB), Brasilia, Brazil
| | - Marcio Garrison Dytz
- School of Medicine, Faculty of Education and Health Sciences, University Center of Brasilia (UniCEUB), Brasilia, Brazil.
- Endocrinology Division, Department of Intern Medicine, Sobradinho Regional Hospital, Brasilia, Brazil.
- Endocrinology and Metabolism Medical Residency, Superior School of Health Sciences (ESCS), Brasilia, Brazil.
- Institute of Diabetes and Endocrinology of Brasilia, SHS Qd. 6 Cj. A Bl. E Sl 1119, Brasilia, DF, 70316-902, Brazil.
| |
Collapse
|
|
46
|
Abstract
Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.
Collapse
|
|
47
|
Shelton CA, Grubs RE, Umapathy C, Yadav D, Whitcomb DC. Impact of hereditary pancreatitis on patients and their families. J Genet Couns 2020; 29:971-982. [PMID: 32026589 DOI: 10.1002/jgc4.1221] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/08/2020] [Accepted: 01/12/2020] [Indexed: 12/15/2022]
Abstract
Hereditary pancreatitis (HP), a highly penetrant (~80%) autosomal dominant disease associated with PRSS1 variants, causes acute pancreatitis in childhood and chronic pancreatitis by early adulthood. Other clinical features include pain, diabetes, and risk of pancreatic cancer. HP kindreds were prospectively recruited from 1995 to 2015. At enrollment, study participants completed medical and family history questionnaires, and provided samples for genotyping. Participants were recontacted between 2015 and 2017 and asked to complete a survey on concerns and experiences related to HP, PRSS1 testing, and genetic counseling. Data were analyzed with descriptive and thematic methods. Thirty-nine affected participants with HP and 21 unaffected family members completed the survey. Among unaffected family members, 'worry' and 'helplessness' were frequently described as the most difficult problem in their family because of HP, particularly with regard to pain. Three participants described the impact of drug addiction on their family. 'School or work limitations' was the leading financial concern, with 65.5% (36/55) rating it as 'moderately' or 'extremely important.' Unexpectedly, only 62% (21/34) of affected PRSS1 carriers believed the chance for a parent to pass HP to his or her children was 50%, whereas 18% (6/34) believed the chance was 100%. The impact of HP on individuals and families varied, which may reflect the highly unpredictable nature of HP severity and outcomes. Based on current and previously reported findings, an overview of important issues for genetic counselors to consider for counseling HP families is included.
Collapse
Affiliation(s)
- Celeste A Shelton
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.,Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Robin E Grubs
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Chandraprakash Umapathy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Dhiraj Yadav
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David C Whitcomb
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.,Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| |
Collapse
|
|
48
|
Aslam M, Vijayasarathy K, Talukdar R, Sasikala M, Nageshwar Reddy D. Reduced pancreatic polypeptide response is associated with early alteration of glycemic control in chronic pancreatitis. Diabetes Res Clin Pract 2020; 160:107993. [PMID: 31877344 DOI: 10.1016/j.diabres.2019.107993] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/25/2019] [Accepted: 12/20/2019] [Indexed: 01/24/2023]
Abstract
AIM To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT). METHODS We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant. RESULTS Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls. CONCLUSION Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.
Collapse
Affiliation(s)
- Mohsin Aslam
- Clinical Endocrinologist, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India.
| | | | - Rupjyothi Talukdar
- Clinical Pancreatologist, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India
| | - M Sasikala
- Director, Research, Institute of Basic Sciences and Translational Research, Asian Healthcare Foundation, Somajiguda, Hyderabad, India
| | - D Nageshwar Reddy
- Chairman and Chief of Gastroenterology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, India
| |
Collapse
|
|
49
|
Diabetes Mellitus in Children with Acute Recurrent and Chronic Pancreatitis: Data From the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort. J Pediatr Gastroenterol Nutr 2019; 69:599-606. [PMID: 31651815 PMCID: PMC6834233 DOI: 10.1097/mpg.0000000000002482] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry. METHODS We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373). RESULTS Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3-5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33-17.05)], coexisting autoimmune disease [OR 3.94 (0.88-13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)]. CONCLUSION Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.
Collapse
|
|
50
|
Muller N, Sarantitis I, Rouanet M, de Mestier L, Halloran C, Greenhalf W, Férec C, Masson E, Ruszniewski P, Lévy P, Neoptolemos J, Buscail L, Rebours V. Natural history of SPINK1 germline mutation related-pancreatitis. EBioMedicine 2019; 48:581-591. [PMID: 31628023 PMCID: PMC6838417 DOI: 10.1016/j.ebiom.2019.09.032] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 09/29/2019] [Accepted: 09/30/2019] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND The aim was to describe genetic, clinical and morphological features in a large, multicentre European cohort of patients with SPINK1 related pancreatitis, in comparison with patients with idiopathic pancreatitis (IP). METHODS All SPINK1 mutation carriers with pancreatic symptoms from two French and one English centers were included. Patients with IP were included in a control group. Genetic, clinical, radiological and biochemical data were collected. FINDINGS 209 and 302 patients were included in the SPINK1 and control groups (median follow-up: 8.3 years (3.7-17.4) vs 5.3 (2.5-8.8)). The median age at onset of symptoms was 20.1 years (17.5-22.8) in the SPINK1 group versus 41.2 (35.2-45.2). The age of exocrine pancreatic insufficiency (EPI) onset in the SPINK1 group was 49.5 (44.5-54.6) years vs. 65.2 (62.1-68.3), p < 0.001. SPINK1 patients with EPI were 5.3%, 14.7%, 28.3% and 52.4% at 20, 30, 40 and 50 years. Diabetes occurred 37.7 (33.3-42.1) years following the onset of symptoms in the SPINK1 group vs. 30.6 (17.3-43.8) (p = 0.002). SPINK1 patients with diabetes were 7.8%, 13.4%, 26.3% and 43.4% at 30, 40, 50 and 60 years. Seven patients (3.3%) developed pancreatic cancer in the SPINK1 group (versus 3 (0.99%), p = 0.1), at a median age of 60 vs 66 years. The cancer risk was 0.8% before 50 years, 11.9%, 27.7%, 51.8% at 60, 70 and 80 years and was 12 times higher than in controls (Cox HR 12.0 (3.0-47.8), p < 0.001). INTERPRETATION SPINK1 related pancreatitis is associated with earlier onset and pancreatic insufficiencies. p.N34S SPINK1 may well be associated with cancer.
Collapse
Affiliation(s)
- Nelly Muller
- Department of Gastroenterology and Pancreatology, Beaujon Hospital, APHP, Clichy, and Paris-Diderot University, Paris, France
| | - Ioannis Sarantitis
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Royal Liverpool University Hospital, Liverpool, England United Kingdom
| | - Marie Rouanet
- Department of Gastroenterology and Pancreatology, INSERM U1037, University of Toulouse 3, CHU Rangueil, Toulouse, France
| | - Louis de Mestier
- Department of Gastroenterology and Pancreatology, Beaujon Hospital, APHP, Clichy, and Paris-Diderot University, Paris, France
| | - Christopher Halloran
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Royal Liverpool University Hospital, Liverpool, England United Kingdom
| | - William Greenhalf
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Royal Liverpool University Hospital, Liverpool, England United Kingdom
| | - Claude Férec
- UMR1078 Génétique, Génomique Fonctionnelle et Biotechnologies, INSERM, EFS - Bretagne, Université de Brest, CHRU Brest, Brest, France
| | - Emmanuelle Masson
- UMR1078 Génétique, Génomique Fonctionnelle et Biotechnologies, INSERM, EFS - Bretagne, Université de Brest, CHRU Brest, Brest, France
| | - Philippe Ruszniewski
- Department of Gastroenterology and Pancreatology, Beaujon Hospital, APHP, Clichy, and Paris-Diderot University, Paris, France
| | - Philippe Lévy
- Department of Gastroenterology and Pancreatology, Beaujon Hospital, APHP, Clichy, and Paris-Diderot University, Paris, France
| | - John Neoptolemos
- Department of General Surgery and transplantation, University of Heidelberg, Heidelberg, Germany
| | - Louis Buscail
- Department of Gastroenterology and Pancreatology, INSERM U1037, University of Toulouse 3, CHU Rangueil, Toulouse, France
| | - Vinciane Rebours
- Department of Gastroenterology and Pancreatology, Beaujon Hospital, APHP, Clichy, and Paris-Diderot University, Paris, France.
| |
Collapse
|