88 88 Lundberg AH, Eubanks JW III, Henry J, et al. Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo. Pancreas 2000; 21(1):41–51.
89 89 Gloor B, Blinman TA, Rigberg DA, et al. Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats. Pancreas 2000; 21(4):414–420.
90 90 Gloor B, Todd KE, Lane JS, et al. Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice. J Gastrointest Surg 1998; 2(5):430–435.
91 91 Huber W, Algul H, Lahmer T, et al. Pancreatitis cytosorbents (CytoSorb) inflammatory cytokine removal: a prospective study (PACIFIC). Medicine (Baltimore) 2019; 98(4):e13044.
92 92 Andrade‐Davila VF, Chavez‐Tostado M, Davalos‐Cobian C, et al. Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography: results of a controlled clinical trial. BMC Gastroenterol 2015; 15:85.
93 93 Mansour‐Ghanaei F, Joukar F, Taherzadeh Z, et al. Suppository naproxen reduces incidence and severity of post‐endoscopic retrograde cholangiopancreatography pancreatitis: randomized controlled trial. World J Gastroenterol 2016; 22(21):5114–5121.
94 94 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut 2001; 48(1):62–69.
95 95 Folch E, Closa D, Prats N, et al. Leukotriene generation and neutrophil infiltration after experimental acute pancreatitis. Inflammation 1998; 22(1):83–93.
96 96 Inoue S, Nakao A, Kishimoto W, et al. Anti‐neutrophil antibody attenuates the severity of acute lung injury in rats with experimental acute pancreatitis. Arch Surg 1995; 130(1):93–98.
97 97 Murakami H, Nakao A, Kishimoto W, et al. Detection of O2– generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis. Surgery 1995; 118(3):547–554.
98 98 Bhatia M, Saluja AK, Hofbauer B, et al. The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis‐associated lung injury. Int J Pancreatol 1998; 24(2):77–83.
99 99 Steele CW, Karim SA, Foth M, et al. CXCR2 inhibition suppresses acute and chronic pancreatic inflammation. J Pathol 2015; 237(1):85–97.
100 100 Malla SR, Karrman Mardh C, Gunther A, et al. Effect of oral administration of AZD8309, a CXCR2 antagonist, on the severity of experimental pancreatitis. Pancreatology 2016; 16(5):761–769.
101 101 Bhatia M, Hegde A. Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury. Regul Pept 2007; 138(1):40–48.
102 102 Irie Y, Tsubota M, Ishikura H, et al. Macrophage‐derived HMGB1 as a pain mediator in the early stage of acute pancreatitis in mice: targeting RAGE and CXCL12/CXCR4 axis. J Neuroimmune Pharmacol 2017; 12(4):693–707.
103 103 Wetterholm E, Linders J, Merza M, et al. Platelet‐derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. Transl Res 2016; 176:105–118.
104 104 Sakuma Y, Kodama Y, Eguchi T, et al. Chemokine CXCL16 mediates acinar cell necrosis in cerulein induced acute pancreatitis in mice. Sci Rep 2018; 8(1):8829.
105 105 Merza M, Hartman H, Rahman M, et al. Neutrophil extracellular traps induce trypsin activation, inflammation, and tissue damage in mice with severe acute pancreatitis. Gastroenterology 2015; 149(7):1920–1931.e8.
106 106 Leppkes M, Maueroder C, Hirth S, et al. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis. Nat Commun 2016; 7:10973.
107 107 Madhi R, Rahman M, Taha D, et al. Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis. J Cell Physiol 2019; 234(7):11850–11860.
108 108 Murthy P, Singhi AD, Ross MA, et al. Enhanced neutrophil extracellular trap formation in acute pancreatitis contributes to disease severity and is reduced by chloroquine. Front Immunol 2019; 10:28.
109 109 Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989; 245(4922):1059–1065.
110 110 Gonska T. Genetic predisposition in pancreatitis. Curr Opin Pediatr 2018; 30(5):660–664.
111 111 Hegyi P, Wilschanski M, Muallem S, et al. CFTR: a new horizon in the pathomechanism and treatment of pancreatitis. Rev Physiol Biochem Pharmacol 2016; 170:37–66.
112 112 Ooi CY, Durie PR. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros 2012; 11(5):355–362.
113 113 Kumar S, Ooi CY, Werlin S, et al. Risk factors associated with pediatric acute recurrent and chronic pancreatitis: lessons from INSPPIRE. JAMA Pediatr 2016; 170(6):562–569.
114 114 Madacsy T, Pallagi P, Maleth J. Cystic fibrosis of the pancreas: the role of CFTR channel in the regulation of intracellular Ca2+ signaling and mitochondrial function in the exocrine pancreas. Front Physiol 2018; 9:1585.
115 115 Zeng M, Szymczak M, Ahuja M, et al. Restoration of CFTR activity in ducts rescues acinar cell function and reduces inflammation in pancreatic and salivary glands of mice. Gastroenterology 2017; 153(4):1148–1159.
116 116 Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del‐CFTR protein processing defect in vitro by the investigational drug VX‐809. Proc Natl Acad Sci USA 2011; 108(46):18843–18848.
13 Indication and Optimal Timing of ERCP in Acute Pancreatitis
Theodor Voiosu1, Ivo Boškoski2, and Guido Costamagna2
1 Gastroenterology Department, Colentina Clinical Hospital; and Internal Medicine Department, Carol Davila School of Medicine, Bucharest, Romania
2 Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCSS; and Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Rome, Italy
Introduction
Acute pancreatitis (AP) is an inflammatory disease of the pancreas that can cause local injury sometimes accompanied by a severe systemic inflammatory response which can lead to multiple organ dysfunction. AP is usually caused by either excessive alcohol intake or cholelithiasis (80%), with a minority of cases accounted for by various other conditions such as trauma, drugs, predisposing genetic conditions, autoimmune disease, or pancreatic tumours [1]. Over the past decades, as our understanding of the pathophysiology of AP has been refined, so too has our therapeutic armamentarium. However, despite this progress, AP still has an associated mortality estimated at around 5% [2], with severe cases requiring prolonged hospitalization due to local and systemic complications. The most notable paradigm shift in the treatment of AP has been our understanding that conservative medical therapy should represent the mainstay of treatment in most cases and that invasive therapies, especially surgery, should be avoided whenever possible [3].
ERCP in the Setting of Acute Biliary Pancreatitis
The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute biliary pancreatitis (ABP) of biliary origin has been the focus of much research in recent years. Two main issues have been extensively debated: which patients with ABP have an indication for ERCP and when should endoscopy be performed? A recent study shows that around 15% of stones demonstrated during an acute attack pass spontaneously with