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Pancreas Divisum: Evaluation and Treatment of a Persistently Controversial Anatomic Finding

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Pancreas Divisum: Evaluation and Treatment of a Persistently Controversial Anatomic Finding FRONTIERS IN ENDOSCOPY, SERIES #61 FRONTIERS IN ENDOSCOPY, SERIES #61 Douglas G. Adler MD, FACG, AGAF, FASGE, Series Editor Pancreas Divisum: Evaluation and Treatment of a Persistently Controversial Anatomic Finding Taylor Frost Douglas G. Adler INTRODUCTION ancreas divisum (literally, “divided pancreas”) condition.1 CFTR mutations may be present in is the most common anatomic variant of the up to 22% of patients with pancreas divisum who pancreas and is thought to exist in 5-10% of develop pancreatitis.2 P 36,37 the population. Pancreas divisum is the result of The majority of patients with pancreas divisum the failed fusion of the dorsal and ventral pancreatic will remain clinically asymptomatic and may buds early in development, resulting in the majority only be diagnosed incidentally in the context of of the pancreas being drained through the minor an imaging study ordered for another indication. papilla. (Figure 1) In patients with normal anatomy, However, some patients may be found to have the majority of the pancreas drains through the pancreas divisum in the setting of a history of, major papilla. More formally stated, in patients or investigation into, episodes of pancreatitis.3 It with pancreas divisum, the variant pancreatic has been proposed that a relatively stenotic minor ductal anatomy leads to the relatively large dorsal papilla may predispose patients with pancreas pancreas segment being drained through the minor divisum to recurrent episodes of pancreatitis.15 As papilla while the smaller ventral bud drains through such, in some cases patients are recommended to the major papilla. There is no known etiology undergo therapy for pancreas divisum, usually in the for pancreas divisum however, some genetic form of endoscopic minor papilla sphincterotomy abnormalities including mutations in the Cystic and/or endoscopic pancreatic duct stenting and, Fibrosis Transmembrane Conductance Regulator rarely, via surgical intervention. (Figure 2) This (CFTR) and Serine Protease Inhibitor Kazal-type approach can be technically challenging, remains 1 (SPINK1) genes have been associated with the controversial, and is still being debated in the literature. This review article will focus on the Taylor Frost MD, Douglas G. Adler MD, FACG, literature regarding endoscopic intervention for AGAF, FASGE, University of Utah School of symptomatic pancreas divisum and briefly touch Medicine, Department of Medicine, Division upon the role of surgical intervention for definitive of Gastroenterology, Salt Lake City, UT management. 20 PRACTICAL GASTROENTEROLOGY • APRIL 2020 Pancreas Divisum: Evaluation and Treatment of a Persistently Controversial Anatomic Finding FRONTIERS IN ENDOSCOPY, SERIES #61 FRONTIERS IN ENDOSCOPY, SERIES #61 Treatment: Endoscopic Intervention conducted a prospective randomized controlled Endoscopic therapy for symptomatic pancreas trial of 19 patients with symptomatic pancreas divisum has been well documented since the early divisum thought to be due to recurrent acute 1980’s. However, given the relative rarity of the pancreatitis. In this study the authors found that condition, there has been a paucity of high quality patients who underwent endoscopic dorsal duct and well-defined studies that evaluate the efficacy dilation followed by stent placement for one year of endoscopic intervention in this complex and had nearly a 100% response rate with only one somewhat difficult-to-study group of patients. episode of recurrent pancreatitis (due to stent Furthermore, the modality of intervention has occlusion), no hospitalizations, and significantly evolved over this time period as well and has fewer emergency room visits for abdominal pain included minor and major papilla cannulation compared to controls. In addition, the patients with balloon dilation, minor papilla stenting and who underwent endoscopic intervention reported a combination of minor papilla sphincterotomy subjective improvements in symptoms and general and stenting.4,5,6,7,8,9,10,11,12,13 overall well being. Unfortunately, these results As a clinical entity, patients with symptomatic have not entirely been reflected elsewhere in pancreas divisum often manifest in three groups, the literature although most studies are difficult which include recurrent acute pancreatitis, chronic to interpret given less well-defined patient pancreatitis, and pancreatic-type pain. It should be populations, varying definitions of successful stressed that the majority of patients with pancreas endoscopic treatment, and a lack of long-term divisum will be asymptomatic. The particular follow-up. Furthermore, this study also did not manifestation of pancreas divisum encountered include minor papilla sphincterotomy, thus limiting clinically is important as it may predict long its generalizability. term response to both endoscopic and surgical Several retrospective studies that utilized interventions.14 sphincterotomy in combination with or without The definition of recurrent acute pancreatitis pancreatic duct stenting have described clinical varies depending on the study but is optimally defined success rates ranging from 53-84% after a single as pancreas divisum with two or more episodes ERCP session in patients with recurrent acute of pancreatitis, a serum amylase or lipase level pancreatitis that was felt to be due to pancreas greater than three times the upper limit of normal, divisum.12,17,18,19,20 There is an additional study abdominal pain, and imaging that is suggestive of that suggests that this initial success rate may pancreatic inflammation without chronic changes. be increased with subsequent ERCP sessions, If abdominal imaging demonstrates morphological but this approach is uncommonly undertaken in changes to the pancreatic duct or parenchyma then the absence of recurrent stricturing at the site chronic pancreatitis is more likely to be present. of the minor papilla.21 A recent meta-analysis If none of these criteria are present but the patient demonstrated a pooled response rate of 76% in continues to experience abdominal pain that is patients with recurrent acute pancreatitis who characteristically similar to that of pancreatitis then underwent minor papilla sphincterotomy, minor pancreatic-type pain can be considered. papilla sphincteroplasty, dorsal duct stenting, or a combination procedure. In this study, the rate of Recurrent Acute Pancreatitis improvement following endoscopic intervention It has been hypothesized that recurrent acute relied upon the individual study definition of pancreatitis can develop secondary to the reflux success, which may limit the applicability of the of pancreatic secretions across the dorsal pancreatic results. A subgroup of patients in this meta-analysis duct due to a relatively stenotic minor papilla who underwent dorsal duct stenting alone without and, although manometric data has demonstrated sphincterotomy experienced higher rates of success mixed results, endoscopic intervention has been when compared to those who underwent combined of some benefit in select patients with recurrent sphincterotomy with stenting.22 acute pancreatitis.15,4,16 In perhaps the most well Although few in number, studies evaluating described study in the literature, Lans et al. (1992) (continued on page 28) PRACTICAL GASTROENTEROLOGY • APRIL 2020 21 Pancreas Divisum: Evaluation and Treatment of a Persistently Controversial Anatomic Finding FRONTIERS IN ENDOSCOPY, SERIES #61 (continued from page 21) has been demonstrated.18,28,29 A meta-analysis of the long-term efficacy of endoscopic intervention 10 studies with 131 patients estimated a pooled in patients with pancreas divisum suggest that response rate of 48% although the effect of improvement in symptoms may be sustained in endoscopic intervention was considered to be those who initially respond to therapy with long- equivocal and no long-term data are available.22 term response rates ranging from 50-85%.12,23 Furthermore, there has been no difference demonstrated between patients who undergo Chronic Pancreatitis sphincterotomy and stenting verse stenting alone Evidence for endoscopic therapy in patients with in patients with pancreatic type-pain.21 chronic pancreatitis and pancreas divisum is sparse. Taken as a whole, endoscopic intervention for Some studies have reported no improvement in symptomatic pancreas divisum appears to be of symptoms following endoscopic therapy while most benefit in those with well-defined recurrent others have demonstrated long-term response acute pancreatitis without another clear etiology. rates between 30-50% at five years.4,24,21 It is There is some evidence that patients with chronic somewhat difficult to reconcile these diverse pancreatitis may benefit from endoscopic therapy; success rates. Typically, response rates are however, a large portion may still progress to defined as a reduction in subjective pain level, surgical intervention or require multiple ERCP reduced narcotic use, or a reduction in hospital sessions. In patients with pancreatic type-pain admissions. It should be noted that up to 45% of endoscopic therapy is unlikely to yield any benefit patients may require surgical management within and long-term data are lacking. 5 years of the initial endoscopic intervention.10 The potential benefits of endoscopic Dorsal duct dilation on imaging may reflect more intervention must be weighed against the known severe pancreatic disease. Distal intrapancreatic complications associated with minor papilla bile duct strictures have been reported in advanced
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