{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:46:19Z","timestamp":1791549979657,"version":"4.3.4"},"reference-count":87,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:00:00Z","timestamp":1608940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor, and Welfare of Japan","award":["19FC1008"],"award-info":[{"award-number":["19FC1008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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\u201350% of pediatric cases and 28\u201380% 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.<\/jats:p>","DOI":"10.3390\/diagnostics11010031","type":"journal-article","created":{"date-parts":[[2020,12,27]],"date-time":"2020-12-27T20:04:58Z","timestamp":1609099498000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic Abnormalities in Pancreatitis: An Update on Diagnosis, Clinical Features, and Treatment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9969-3454","authenticated-orcid":false,"given":"Mitsuyoshi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-7058","authenticated-orcid":false,"given":"Kei","family":"Minowa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Isayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ng1096-141","article-title":"Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene","volume":"14","author":"Whitcomb","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jpeds.2017.03.063","article-title":"Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations","volume":"186","author":"Giefer","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s00535-017-1388-0","article-title":"Nationwide survey of hereditary pancreatitis in Japan","volume":"53","author":"Masamune","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1038\/ajg.2010.193","article-title":"Genetic; epidemiological; and clinical aspects of hereditary pancreatitis, a population-based cohort study in Denmark","volume":"105","author":"Joergensen","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/gut.2008.149179","article-title":"The natural history of hereditary pancreatitis, a national series","volume":"58","author":"Rebours","year":"2009","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1053\/j.gastro.2018.11.081","article-title":"Genetics, Cell Biology, and Pathophysiology of Pancreatitis","volume":"156","author":"Mayerle","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ebiom.2019.09.032","article-title":"Natural history of SPINK1 germline mutation related-pancreatitis","volume":"48","author":"Muller","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0016-5085(52)80120-9","article-title":"Pedigree of a family with hereditary chronic relapsing pancreatitis","volume":"21","author":"Comfort","year":"1952","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/0002-9343(62)90232-2","article-title":"Hereditary pancreatitis. Description of a fifth kindred and summary of clinical features","volume":"33","author":"Gross","year":"1962","journal-title":"Am. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene, cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJM199809033391002","article-title":"Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis","volume":"339","author":"Cohn","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJM199809033391001","article-title":"Mutations of the cystic fibrosis gene in patients with chronic pancreatitis","volume":"339","author":"Sharer","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/76088","article-title":"Mutations in the gene encoding the serine protease inhibitor; Kazal type 1 are associated with chronic pancreatitis","volume":"25","author":"Witt","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Felderbauer, P., Hoffmann, P., Einwachter, H., Bulut, K., Ansorge, N., Schmitz, F., and Schmidt, W.E. (2003). A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations. BMC Gastroenterol., 3.","DOI":"10.1186\/1471-230X-3-34"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/00365520510024214","article-title":"Mutations in the calcium-sensing receptor, a new genetic risk factor for chronic pancreatitis?","volume":"41","author":"Felderbauer","year":"2006","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.3748\/wjg.14.4486","article-title":"Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population, role of serine protease inhibitor Kazal 1type and alcohol","volume":"14","author":"Muddana","year":"2008","journal-title":"World. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1097\/MPA.0000000000000361","article-title":"Overrepresentation of Rare CASR Coding Variants in a Sample of Young French Patients with Idiopathic Chronic Pancreatitis","volume":"44","author":"Masson","year":"2015","journal-title":"Pancreas"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/ng.2007.44","article-title":"Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis","volume":"40","author":"Rosendahl","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/ng.2466","article-title":"Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis","volume":"44","author":"Whitcomb","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/ng.2730","article-title":"Variants in CPA1 are strongly associated with early onset chronic pancreatitis","volume":"45","author":"Witt","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/ng.3249","article-title":"A recombined allele of the lipase gene CEL and its pseudogene CELP confers susceptibility to chronic pancreatitis","volume":"47","author":"Fjeld","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1136\/gutjnl-2017-314454","article-title":"Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis","volume":"67","author":"Rosendahl","year":"2018","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"974","DOI":"10.14309\/ajg.0000000000000051","article-title":"Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis","volume":"114","author":"Lasher","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1053\/j.gastro.2020.01.005","article-title":"Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis","volume":"158","author":"Masamune","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ng1708","article-title":"Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction","volume":"38","author":"Raeder","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1136\/gutjnl-2017-313816","article-title":"A novel p.Ser282Pro CPA1 variant is associated with autosomal dominant hereditary pancreatitis","volume":"66","author":"Kujko","year":"2017","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ng1797","article-title":"A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis","volume":"38","author":"Witt","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S226","DOI":"10.1016\/S0016-5107(02)70016-3","article-title":"Epidemiology; natural history; and predictors of disease outcome in acute and chronic pancreatitis","volume":"56","author":"Banks","year":"2002","journal-title":"Gastrointest. Endosc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.pan.2020.03.014","article-title":"International Consensus Guidelines for Risk Factors 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","volume":"20","author":"Hegyi","year":"2020","journal-title":"Pancreatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1111\/j.1572-0241.2002.05833.x","article-title":"Acute pancreatitis in children","volume":"97","author":"DeBanto","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1440-1746.2006.04246.x","article-title":"Childhood pancreatitis","volume":"21","author":"Nydegger","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/ped.12449","article-title":"Scoring system for the prediction of severe acute pancreatitis in children","volume":"57","author":"Suzuki","year":"2015","journal-title":"Pediatr. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/MPG.0000000000001320","article-title":"Genetic Analysis of Japanese Children With Acute Recurrent and Chronic Pancreatitis","volume":"63","author":"Saito","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1001\/jama.2019.19411","article-title":"Diagnosis and Management of Chronic Pancreatitis, A Review","volume":"322","author":"Singh","year":"2019","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1159\/000055840","article-title":"Genetic testing for hereditary pancreatitis, guidelines for indications; counselling; consent and privacy issues","volume":"1","author":"Ellis","year":"2001","journal-title":"Pancreatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.gtc.2007.03.007","article-title":"Genetic counseling for nonsyndromic pancreatitis","volume":"36","author":"Fink","year":"2007","journal-title":"Gastroenterol. Clin. North. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S1542-3565(04)00013-8","article-title":"Clinical and genetic characteristics of hereditary pancreatitis in Europe","volume":"2","author":"Howes","year":"2004","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/01.mpg.0000221894.44124.8e","article-title":"Usefulness of nonbreath-hold 1-shot magnetic resonance cholangiopancreatography for the evaluation of choledochal cyst in children","volume":"42","author":"Suzuki","year":"2006","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1152\/physrev.00011.2011","article-title":"Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion","volume":"92","author":"Lee","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02787524","article-title":"New concepts in understanding the pathophysiology of chronic pancreatitis","volume":"24","author":"Freedman","year":"1998","journal-title":"Int. J. Pancreatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1136\/jmg.2003.014456","article-title":"Genetic evidence for CFTR dysfunction in Japanese, background for chronic pancreatitis","volume":"41","author":"Fujiki","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1053\/gast.2001.29673","article-title":"Cystic fibrosis gene mutations and pancreatitis risk, relation to epithelial ion transport and trypsin inhibitor gene mutations","volume":"121","author":"Noone","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1136\/gutjnl-2011-300645","article-title":"CFTR; SPINK1; CTRC and PRSS1 variants in chronic pancreatitis, is the role of mutated CFTR overestimated?","volume":"62","author":"Rosendahl","year":"2013","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1053\/j.gastro.2010.10.045","article-title":"Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis","volume":"140","author":"Schneider","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1053\/gast.1997.v113.pm9322498","article-title":"Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis","volume":"113","author":"Gorry","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20701","DOI":"10.1074\/jbc.M112.360065","article-title":"Increased activation of hereditary pancreatitis-associated human cationic trypsinogen mutants in presence of chymotrypsin C","volume":"287","author":"Szabo","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11879","DOI":"10.1074\/jbc.M600124200","article-title":"Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen","volume":"281","author":"Nemoda","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/humu.20853","article-title":"Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen, a novel disease mechanism","volume":"30","author":"Kereszturi","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1136\/gutjnl-2012-304331","article-title":"Functional effects of 13 rare PRSS1 variants presumed to cause chronic pancreatitis","volume":"63","author":"Schnur","year":"2014","journal-title":"Gut"},{"key":"ref_50","first-page":"424","article-title":"A comparison of serum trypsinogen-2 and trypsin-2-alpha1-antitrypsin complex with lipase and amylase in the diagnosis and assessment of severity in the early phase of acute pancreatitis","volume":"96","author":"Hedstrom","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1111\/j.1440-1746.2006.04594.x","article-title":"SPINK1 gene mutations and pancreatitis in Japan","volume":"21","author":"Shimosegawa","year":"2006","journal-title":"J. Gastroentero. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/j.1572-0241.2002.05673.x","article-title":"Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis","volume":"97","author":"Truninger","year":"2002","journal-title":"Am. J. Gastroenterol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s005350200156","article-title":"Functional analysis of recombinant pancreatic secretory trypsin inhibitor protein with amino-acid substitution","volume":"37","author":"Kuwata","year":"2002","journal-title":"J. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1136\/gut.2006.115725","article-title":"Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation","volume":"56","author":"Kiraly","year":"2007","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/MPG.0b013e31820e2126","article-title":"High incidence of PRSS1 and SPINK1 mutations in Korean children with acute recurrent and chronic pancreatitis","volume":"52","author":"Lee","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1159\/000086535","article-title":"Mutations in the serine protease inhibitor Kazal Type 1 (SPINK1) gene in Japanese patients with pancreatitis","volume":"5","author":"Kume","year":"2005","journal-title":"Pancreatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/MPA.0b013e31818d1b90","article-title":"Analysis of PRSS1 and SPINK1 mutations in Korean patients with idiopathic and familial pancreatitis","volume":"38","author":"Oh","year":"2009","journal-title":"Pancreas"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/mpa.0b013e3180335fd0","article-title":"N34S mutation in the SPINK1 gene is not associated with alternative splicing","volume":"34","author":"Masamune","year":"2007","journal-title":"Pancreas"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1136\/gutjnl-2012-303090","article-title":"Comprehensive functional analysis of chymotrypsin C (CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk","volume":"62","author":"Beer","year":"2013","journal-title":"Gut"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00439-007-0459-3","article-title":"Association of rare chymotrypsinogen C (CTRC) gene variations in patients with idiopathic chronic pancreatitis","volume":"123","author":"Masson","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Suzuki, M., Minowa, K., Isayama, H., and Shimizu, T. (2020). Acute Recurrent and Chronic Pancreatitis in Children. Pediatr Int.","DOI":"10.1111\/ped.14415"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ceca.2017.04.006","article-title":"TRPV6, From identification to function","volume":"67","author":"Wissenbach","year":"2017","journal-title":"Cell. Calcium."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19461","DOI":"10.1074\/jbc.M009895200","article-title":"Expression of CaT-like; a novel calcium-selective channel; correlates with the malignancy of prostate cancer","volume":"276","author":"Wissenbach","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid","volume":"366","author":"Brown","year":"1993","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/gut.51.5.705","article-title":"Extracellular calcium sensing receptor in human pancreatic cells","volume":"51","author":"Racz","year":"2002","journal-title":"Gut"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1046\/j.1432-1033.2003.03581.x","article-title":"Human anionic trypsinogen, properties of autocatalytic activation and degradation and implications in pancreatic diseases","volume":"270","author":"Kukor","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1053\/j.gastro.2018.06.041","article-title":"Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice","volume":"155","author":"Jancso","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/MPG.0000000000002405","article-title":"Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children, Report from INSPPIRE","volume":"69","author":"Liu","year":"2019","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1572-0241.2007.01597.x","article-title":"Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis, a national exhaustive series","volume":"103","author":"Rebours","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/s41395-018-0194-5","article-title":"Hereditary Pancreatitis in the United States, Survival and Rates of Pancreatic Cancer","volume":"113","author":"Shelton","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0049-3848(86)90227-6","article-title":"Consumptive coagulopathy; fibrinolysis and protease-antiprotease interactions during acute human pancreatitis","volume":"41","author":"Lasson","year":"1986","journal-title":"Thromb. Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Dumnicka, P., Maduzia, D., Ceranowicz, P., Olszanecki, R., Drozdz, R., and Kusnierz-Cabala, B. (2017). The Interplay between Inflammation; Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis, Clinical Implications. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020354"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-3-642-23056-1_3","article-title":"The anticoagulant and antithrombotic mechanisms of heparin","volume":"207","author":"Gray","year":"2012","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/0167-4838(94)90054-X","article-title":"Heparin-induced structural and functional alterations of bovine trypsin","volume":"1207","author":"Finotti","year":"1994","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0049-3848(92)90126-U","article-title":"The inhibition of thrombin and chymotrypsin by heparin-cofactor II","volume":"68","author":"Struss","year":"1992","journal-title":"Thromb. Res."},{"key":"ref_76","first-page":"368","article-title":"The inhibitory effect of heparin on trypsinogen activation with enterokinase","volume":"24","author":"Wolosowicz","year":"1977","journal-title":"Acta. Hepatogastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"642787","DOI":"10.1155\/2012\/642787","article-title":"Isolation of human islets for autologous islet transplantation in children and adolescents with chronic pancreatitis","volume":"2012","author":"Bottino","year":"2012","journal-title":"J. Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.surg.2013.07.003","article-title":"Surgical outcomes after total pancreatectomy and islet cell autotransplantation in pediatric patients","volume":"154","author":"Wilson","year":"2013","journal-title":"Surgery"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.jamcollsurg.2013.12.037","article-title":"Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary\/genetic pancreatitis","volume":"218","author":"Chinnakotla","year":"2014","journal-title":"J. Am. Coll. Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.gie.2013.07.060","article-title":"ERCP in the management of pancreatic diseases in children","volume":"79","author":"Agarwal","year":"2014","journal-title":"Gastrointest. Endosc."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"142","DOI":"10.5946\/ce.2017.102","article-title":"Advanced Therapeutic Gastrointestinal Endoscopy in Children\u2014Today and Tomorrow","volume":"51","author":"Nabi","year":"2018","journal-title":"Clin. Endosc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nrgastro.2014.74","article-title":"Treatment options for chronic pancreatitis","volume":"11","author":"Issa","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1016\/S0140-6736(16)00097-0","article-title":"Chronic pancreatitis","volume":"387","author":"Majumder","year":"2016","journal-title":"Lancet"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.jpedsurg.2014.05.016","article-title":"Therapeutic step-up strategy for management of hereditary pancreatitis in children","volume":"50","author":"Kargl","year":"2015","journal-title":"J. Pediatr. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1055\/s-2005-921069","article-title":"Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis, long-term results","volume":"38","author":"Costamagna","year":"2006","journal-title":"Endoscopy"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"E1215","DOI":"10.1055\/s-0042-115934","article-title":"Prospective pilot study of fully covered self-expandable metal stents for refractory benign pancreatic duct strictures, long-term outcomes","volume":"4","author":"Matsubara","year":"2016","journal-title":"Endosc. Int. Open"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1055\/a-0959-6163","article-title":"Long-term follow-up after multiple plastic stenting for refractory pancreatic duct strictures in chronic pancreatitis","volume":"51","author":"Tringali","year":"2019","journal-title":"Endoscopy"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/1\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:32Z","timestamp":1760179592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/1\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,26]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["diagnostics11010031"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11010031","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,26]]}}}