JOP. J Pancreas (Online) 2017 Mar 30; 18(2):97-100. REVIEW ARTICLE Pancreas Divisum: On Life Support, But Not Quite Dead Dennis Kumral, John Baillie Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA, 23298, USA ABSTRACT Pancreas divisum, the failure of fusion of the dorsal and ventral pancreatic ductal systems in utero, is the most common congenital acute or recurrent pancreatitis. With increasing use of magnetic resonance imaging and magnetic resonance cholangiopancreatography abnormality of the pancreas. The clinical significance of pancreas divisum is often considered when it is found in patients with idiopathic pancreatopathyin the past twenty caused years, by thea stenotic detection minor of pancreaspapilla. Developments divisum is increasingly in the study common of the genetics in patients of pancreatitis undergoing have cross-sectional fueled the debate imaging. as Therapeutic interventions for patients with recurrent acute pancreatitis and pancreas divisum aim to relieve the relative obstructive etiology of recurrent acute pancreatitis should be abandoned. Others have suggested that further study is needed in the understanding of to whether pancreas divisum in itself causes pancreatitis. Some have argued that pancreas divisum is a bystander and that its role as an the association of pancreas divisum with genetic mutations, such as cystic fibrosis transmembrane conductance regulator. Historically, the study of pancreas divisum has been limited to uncontrolled and observational studies with the level of evidence reviewed. This paper will review the anatomy, diagnostic and therapeutic modalities, and developments in the genetics of pancreas divisum to revive the discussion on this much-debated topic. INTRODUCTION in Figure 1 Pancreas divisum is the most common congenital anatomic variant findings in pancreas divisum is illustrated anatomic abnormality of the pancreas. During the sixth . Another anatomic variant, incomplete pancreas divisum, is infrequent, and presents as a narrow and often the fusion of the dorsal and ventral pancreatic buds. The inadequate connection between the dorsal and ventral week of gestation, the pancreas normally develops from reportedpancreatic the ducts, incidence with the of majoritypancreas ofdivisum drainage to occurringbe in the bud develops into the uncinate process. In the majority of via the smaller minor papilla [3]. Autopsy series have dorsal bud forms the head, body, and tail while the ventral pancreas divisum is a congenital anomaly present at birth, of their ductal systems such that the main pancreatic duct order of 5-10% of the general population [4, 5]. Although servesindividuals, as the the path union for of emptying these structures of pancreatic allows forsecretions a fusion it becomes symptomatic [6, 7]. With increasing use of it is often not diagnosed until the fifth decade of life, when normal variant anatomy is present in approximately 30% into the duodenum via the major duodenal papilla. A being diagnosed earlier in asymptomatic patients. cross-sectional diagnostic imaging, pancreas divisum is persists as an accessory pancreatic duct and empties via theof individuals, minor duodenal where papilla the proximal [1]. On thedorsal contrary, pancreatic in typical duct Pancreas divisum, the fusion of the dorsal and ventral acuteThe or clinical recurrent significance pancreatit of pancreas divisum is often considered when it pisancreas found divisumin patients and withdevelopment idiopathic of the dorsal duct draining the majority of the pancreas via pancreatitis in a retrospectiveis. series Cotton of patients[6] first suggestedundergoing a theductal minor systems papilla fails, and forming the ventral two ductdistinct draining conduits only with the endoscopiccorrelation betweenretrograde cholangiopancreatography (ERCP). inferior portion of the head of the pancreas via the major While the overall incidence of p ancreas divisum was papilla [2]. The normal anatomy of the pancreas as well as 3.6% in the series, patients with unexplained recurrent Keywords Gene Expression; Immunotherapy; Pancreatic Neoplasms didpancreatitis not consider had alternativea much higher etiologies incidence for pancreatitis, of 25.6%. AbbreviationsReceived December 2nd, 2016 - Accepted February 08th, 2017 suchAlthough as geneticthis study or wasautoimmune weakened causes, by a referral it did biaslead and to CFTR cystic fibrosis transmembrane conductance further interest in a potential role of pancreas divisum in cholangiopancreatographyregulator; MRI magnetic resonance imaging; RAP recurrent acute the development of acute and recurrent pancreatitis. The Correspondencepancreatitis; s-MRCP John secretin Baillie enhanced magnetic resonance proposed mechanism for pancreatitis in pancreas divisum TelGateway Building, 4th Floor, 1200 E. Marshall St. papilla bearing the responsibility for draining the majority E-mailRichmond, [email protected] Virginia 23298 is an obstructive pancreatopathy, with the narrow minor +804 828-8508 JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 18 No. 2 –Mar of2017. the [ISSN pancreas 1590-8577] by way of the dorsal pancreatic duct [6, 8].97 JOP. J Pancreas (Online) 2017 Mar 30; 18(2):97-100. Figure 1. Pancreatic ductal anatomy variants. et al. [9] performed Therapeutic Interventions andIn an found attempt relatively to quantify increased this, pressuresStaritz in the dorsal duct ERCP with manometry on patients with pancreas divisum relieveTherapeutic the relative interventions obstructive for pancreatopathy patients with causedrecurrent by et al. [10] found no difference in both aacute stenotic pancreatitis minor papilla. (RAP) While and surgicalpancreas intervention divisum aim such to basalas compared and phasic to the manometric ventral duct. pressures However, from the evidence the major is equivocal: Satterfield as minora less papilla invasive sphincteroplasty treatment modality. has been Endotherapy performed with for etand al. minor [11] usedpapilla magnetic in patients resonance with pancreas imaging divisum (MRI) and pancreassome success divisum [15, 16,may 17], include endoscopic dorsal therapy duct pancreaticis favored magneticacute pancreatitis. resonance From cholangiopancreatography an anatomic standpoint, (MRCP) Wang to stent placement [18] or, more frequently, endoscopic support the dorsal obstructive hypothesis by showing that minor papillotomy [19]. In a randomized controlled trial, isolated dorsal pancreatic involvement was more common either dorsal duct stent placement (in 10 patients) or no patients with pancreas divisum were randomized to in patients with pancreatitis and pancreas divisum, 44.74% as compared to 22.22% in controls, with pancreatitis but up of about 30 months, no patients in the stent group intervention in controls (9 patients). With a mean follow- without pancreas divisum. years, the detection of pancreas divisum is increasingly With increasing use of MRI and MRCP in the past twenty required hospitalization for abdominal pain but five out of stentedthe nine patients patients and in the seven control of the group nine control were readmitted patients [20]. for accuracycommon inin patientsthe diagnosis undergoing of pancreas cross-sectional divisum asimaging. ERCP pain management. RAP was documented in one of the ten MRCP has been shown to have the same diagnostic may enhance detection of pancreas divisum by stimulating In a long-term efficacy study endoscopic therapy, twenty- [12]. Furthermore, secretin-enhanced MRCP (S-MRCP) four patients with RAP and underlying pancreas divisum were treated with sphincterotomy of the minor papilla (8 bicarbonate and fluid secretion into the pancreatic ducts, patients) or dorsal duct stent insertion (16 patients). Acute allowing for improved visualization of anatomic features pancreatitis recurred in two of the eight patients treated [13]. A meta-analysis of 10 studies with 1474 patients with sphincterotomy of the minor papilla and there was showed that secretin-enhanced MRCP had increased no recurrence in patients that received a stent with a diagnostic performance with sensitivity of 86% as median duration of follow-up of 39 months. On the other compared to 52% for standard MRCP, thus strengthening hand, complication rate was less significant in the minor the role of non-invasive imaging for the diagnosis of papillotomy group (25%) as compared to the dorsal duct pancreas divisum [14]. With increased access to radiology stent group (44%) [21]. These endoscopic therapies have diagnosisfacilities ofwith pancreas MRI/MRCP divisum. capabilities, these imaging shown clinical benefits in patients with RAP associated with modalities will continue to serve as the new standard in pancreas divisum, while patients with chronic pancreatitis JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 18 No. 2 –Mar associated2017. [ISSN 1590-8577] with pancreas divisum, or abdominal pain 98 JOP. J Pancreas (Online) 2017 Mar 30; 18(2):97-100. Table 1. Level of evidence of cited studies. Genetic Mutations Level of Evidence (based on Pancreas Divisum Studies Oxford Centre for Evidence- (Reference number) Based Medicine) Kleitsch et al IV This argument was further advanced by the observation Langman et al IV that genetic mutations associated with pancreatitis may . 1955 [4] divisum. Pramod et al. [29] found SPINK-1 Cotton et al IV be seen in higher frequencies in patients with pancreas . 1961 [5] Bernard et al. 1990 [7] IV mutations were .