Pancreas Divisum Is Not a Cause of Pancreatitis by Itself But Acts as a Partner of Genetic Mutations

Bertin, C.; Pelletier, Anne-Laure; Vullierme, Marie Pierre; Bienvenu, Thierry; Rebours, Vinciane; Hentic, Olivia; Maire, Frédérique; Hammel, Pascal; Vilgrain, Valérie; Ruszniewski, Philippe; Lévy, Philippe

doi:10.1038/ajg.2011.424

Cited by 219 publications

(122 citation statements)

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“…A legtöbb, divisummal élő betegben nem alakul ki pancreatitis. Azokban, akikben pancreatitis alakul ki, az anatómiai eltérés mellett más rizikófaktor társulá-sát is kell keresni, például genetikai mutáció [4,7,13].…”

Section: Ritka Okokunclassified

Pediatric pancreatitis.Evidence based management guidelines of the Hungarian Pancreatic Study Group

et al. 2015

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A hasnyálmirigy gyulladásos megbetegedése gyermekkorban ritka és etiológiája változatos. Az utóbbi 10-15 évben a gyermekkori pancreatitisek gyakorisága növekedést mutatott világszerte. A betegség korszerű és bizonyítékokon alapuló kezelési útmutatót igényel. A Magyar Hasnyálmirigy Munkacsoport célul tűzte ki, hogy a jelenleg elérhető nemzetközi irányvonalakat, illetve evidenciákat alapul véve a gyermekkori pancreatitis kezelésének kulcskérdései vonatkozásában bizonyítékalapú irányelveket fogalmazzon meg. A Magyar Hasnyálmirigy Munkacsoport által kijelölt előkészítő és konzulens munkacsoport lefordította, és ahol szükségesnek találta, kiegészítette és/vagy módosította a nemzetközi irányelveket. Összesen 8 témakörben (Diagnózis, Etiológia, Prognózis, Képalkotók, Kezelés, Epeúti beavatkozás, Szövődmények, Krónikus pancreatitis) 50 releváns kérdést állított össze. Az evidencia osztályozását az UpToDate ® rendszere alapján határozta meg. Az összeállított irányelvek a 2014. szeptember 12-ei konszenzustalálkozón kerültek bemutatásra és megvitatásra. A résztvevők minden kérdést teljes (95% feletti) egyetértéssel fogadtak el. A Magyar Hasnyálmirigy Munkacsoport kezelési irányelvei az első, bizonyíték alapján készült gyermekkori pancreatitis kezelési útmutató hazánkban. A Magyar Hasnyálmirigy Munkacsoport gyermekkori pancreatitis kezelési irányelvei komoly segítséget nyújtanak a gyermekkori pancreatitis oktatásához, a mindennapi betegellátáshoz és a megfelelő fi nanszírozás kialakításához, ezért bízunk benne, hogy ezen irányelvek minél szélesebb körben alapreferenciaként fognak szolgálni Magyarországon. Orv. Hetil., 2015, 156(8), 308-325.Kulcsszavak: bizonyítékon alapuló orvoslás, kezelési irányelvek, gyermekkori pancreatitis

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Section: Ritka Okokunclassified

Pediatric pancreatitis.Evidence based management guidelines of the Hungarian Pancreatic Study Group

et al. 2015

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“…The frequency of PD in patients with rAP and CP of unknown origin was evaluated by MRCP [23]. The hypothesis of an interaction between anatomical and functional genetic anomalies (SPINK1, PRSS1 or CFTR gene mutation or polymorphism) was studied [23].…”

Section: What Is the Role Of Genetic Mutations In Patients With Pd Whmentioning

confidence: 99%

“…The hypothesis of an interaction between anatomical and functional genetic anomalies (SPINK1, PRSS1 or CFTR gene mutation or polymorphism) was studied [23]. Patients with alcohol induced pancreatitis and subjects who underwent MRCP for non-pancreatic disease were used as controls [23].…”

Section: What Is the Role Of Genetic Mutations In Patients With Pd Whmentioning

confidence: 99%

Pancreatic Divisum: Beyond what is Obvious

2014

Pancreat Disord Ther

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In over 90% of healthy people, the dorsal and ventral endodermal pancreatic buds fuse to form the adult pancreas. However, in about the remaining 10% of the population where the fusion does not occur, pancreatic divisum (PD) results. This indeed is the commonest congenital anomaly of pancreas. The dorsal root usually drains a part of pancreatic head, the body and tail of the pancreas via a minor papilla into the duodenum. The ventral root drains the uncinate process and part of the pancreatic head with the CBD via the major papilla into the duodenum and the two roots are communicated with one another. In classic PD (type1) there is a complete failure of fusion of ducts, and a small ventral duct (Santorini) drains through the larger major papilla, and a larger dorsal duct (Wirsung) drains through the smaller minor papilla. In type 2, there is a complete absence of duct of Wirsung. While in type (incomplete PD), there is a filamentous or tiny caliber communication between the dominant dorsal duct of Wirsung and duct of Santorini. In the western countries, the incomplete PD is uncommon with a reported incidence of 0.13%-0.9%. However recent reports from Japan and Korea show a much higher prevalence of 48% to 52%, of incomplete PD. In patients with a large duct, the majority of the pancreatic secretions pass through the minor papilla (instead of major) resulting in inadequate drainage and pain caused by obstruction. However while these features of PD are relatively well known, there are some aspects of PD, which are not so obvious. These include its true prevalence, its role in development of pancreatitis and carcinoma of pancreas, the genetic abnormalities and its association with pancreatitis in presence of PD and the appropriate management of these patients when symptomatic

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“…There is no compelling evidence for epistasis between SPINK1 and CFTR mutations; the two susceptibility genes seem to act independently in determining the pancreatitis phenotype [26]. CFTR mutations can also contribute to the increased clinical penetrance of anatomical risk factors for chronic pancreatitis such as pancreas divisum [33]. …”

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confidence: 99%

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

Hegyi

2016

Pancreatology

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Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking or bile acids strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis.Corresponding author: Prof. Dr. Peter Hegyi, Doctor of the Hungarian Academy of Sciences, First Department of Medicine, University of Szeged, Koranyi fsr. 8-10, SZEGED, H6720, Hungary, TEL: +3662545200, FAX: +3662545185, MOBILE: +36703751031, hegyi.peter@med.u-szeged.hu. Conflict of interest statement: the authors have no conflict of interest to declare HHS Public Access I. Basics of CFTR a. Biosynthesis and degradationThe cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cyclic AMP (cAMP)-regulated chloride (Cl − )/bicarbonate (HCO 3 − ) channel, expressed in the apical plasma membrane (PM) of secretory epithelia in the airways, pancreas, intestine, reproductive organs and exocrine glands [1]. CFTR consists of two homologous halves, each containing a hexa-helical membrane spanning domain (MSD1 and MSD2) and a nucleotide binding domain (NBD1 and NBD2) (Figure 1). The two halves are connected by the R domain [2]. The NBDs contain conserved ATP-binding sequences: Walker A and B motifs, classifying CFTR as a member of the ATP-binding cassette (ABC) transporter family. Structural, biochemical and functional evidence suggest that the two NBD domains interact and the ATP-binding site of one NBD is complemented by the ABC signature motif of the other [2].While NBD1 folds largely co-translationally, the native fold of NBD2 as well as CFTR are attained post-translationally [3]. Assembly of MSD1, NBD1, R domain and MSD2 is necessary and sufficient to form the minimal folding unit of CFTR [4]. These and other observations support the cooperative domain folding model and ensure the dynamic conformational coupling between the cytosolic NBDs and the pore-forming MSDs in the native molecule and provide a structural explanation for the cooperative domain unfolding, caused by cystic fibrosis (CF) mutations [4].Despite interactions with several cytosolic and endoplasmic reticulum (ER) chapero...

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Pancreas Divisum Is Not a Cause of Pancreatitis by Itself But Acts as a Partner of Genetic Mutations

Cited by 219 publications

References 40 publications

Pediatric pancreatitis.Evidence based management guidelines of the Hungarian Pancreatic Study Group

Pediatric pancreatitis.Evidence based management guidelines of the Hungarian Pancreatic Study Group

Pancreatic Divisum: Beyond what is Obvious

CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

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