Endotherapy in symptomatic pancreas divisum: A systematic review

doi:10.1016/j.pan.2014.05.796

Pancreatology

Volume 14, Issue 4, July–August 2014, Pages 244-250

https://doi.org/10.1016/j.pan.2014.05.796 Get rights and content

Abstract

Pancreas divisum (PD) is the most common congenital variant of the pancreas and has been implicated as a cause of pancreatitis; however, endoscopic treatment is controversial. Our objective was to examine patient response to endotherapy for treatment of symptomatic PD in adult patients in a systematic review of the literature. A systematic review of all case series and case–control studies with ten or more patients undergoing endotherapy for treatment of symptomatic PD indicated by acute recurrent pancreatitis (ARP), chronic pancreatitis (CP), or chronic abdominal pain (CAP) was performed. PubMed, Embase, and Web of Science databases were searched from inception through February 2013 using [pancreas divisum] AND [endoscopic retrograde cholangiopancreatography (ERCP)] OR [endotherapy] OR [endoscopy] as search terms. Importantly, the majority of studies were retrospective in nature, significantly limiting analysis capacity. Main outcomes measures included endotherapy response rate in patients with PD and ARP, CP, or CAP. Twenty-two studies were included in the review, with a total of 838 patients. Response to endoscopy was seen in 528 patients, but response rate varied by clinical presentation. Patients with ARP had a response rate ranging from 43% to 100% (median 76%). Reported response rates were lower in the other two groups, ranging from 21% to 80% (median 42%) for patients with CP and 11%–55% (median 33%) for patients with CAP. Complications reported included perforation, post-endoscopic retrograde cholangiopancreatography pancreatitis, bleeding, and clogged stents. Endotherapy appears to offer an effective treatment option for patients with symptomatic PD, with the best results in patients presenting with ARP.

Introduction

Pancreas divisum (PD) is the most common congenital variant of the pancreas with an overall prevalence of approximately 2.9% [1], although detection rates vary from 4% to 10% in Caucasian populations and 1%–2% in Asian populations [1], [2], [3]. PD occurs due to failure of embryological dorsal and ventral pancreatic duct fusion at 6–8 weeks gestation [4]. Many studies suggest that PD has an etiological role in idiopathic pancreatitis [5], [6], [7]. However, the clinical significance of PD is debated, as most patients are asymptomatic, and less than 10% develop pancreatitis [8], [9], [10]. Recent studies indicate that genetic mutations, particularly in the CFTR gene, may be associated with a predisposition to pancreatitis in patients with PD [11], [12], [13]. This genetic susceptibility may explain why some patients with PD get pancreatitis and others do not [14], [15].

The pathogenesis of pancreatitis in PD is thought to be secondary to minor papilla stenosis, which causes resistance to the flow of pancreatic secretions and leads to increased intraductal pressure. Based on this pathophysiology, endoscopic or surgical minor papilla ductal decompression is used to treat idiopathic pancreatitis or chronic abdominal pain associated with PD. Several methods of endoscopic therapy are commonly used, including minor papillotomy (needle-knife sphincterotomy over a stent or pull-type sphincterotomy), stent placement, and balloon dilation of the minor papilla. Although endotherapy is commonly used for the treatment of symptomatic PD, it is controversial, and the outcome of treatment is debated. The purpose of this systematic review was to assess patient response to endotherapy for the treatment of symptomatic PD with acute recurrent pancreatitis, chronic pancreatitis, or chronic abdominal pain in published case-series and case–control studies including at least ten unique patients.

Section snippets

Study selection

All articles assessing the effectiveness of endotherapy in pancreas divisum in adult patients were selected, and studies with a sample size of ten or more adult patients were included. Studies describing surgical intervention for PD, letters, editorials, and reviews were excluded from analysis. There were no language restrictions. Both full-length and abstract publications were included in the study.

Literature search

A literature search was conducted to identify relevant original articles related to PD and

Results

Twenty-two studies [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37] met criteria for inclusion in our review (Fig. 1), the designs of which are summarized in Table 1. Studies were reported from the United States (n = 17), The Netherlands (n = 1), France (n = 1), Italy (n = 1), Australia (n = 1), and Japan (n = 1). Seventeen studies were retrospective and five were prospective. All studies were case series studies

Discussion

Although PD was first described more than a century ago, detection only increased after the advent of ERCP in the 1970s [38], [39]. Approximately 1%–10% of the population has PD [1], [2], [3], but evidence suggests that only 10% of patients with PD experience symptoms [4], and the role of PD in the aetiology of pancreatitis is debated [8], [9], [10].

PD results from failure of fusion of the dorsal and ventral pancreatic ductal system at 6–8 weeks of gestation and can be categorized as either

Funding support

None.

Disclosure statement

There is no conflict of interest to report on the part of any author.

Author contributions

All authors contributed to the conception and design; analysis and interpretation of the data; drafting of the article; critical revision of the article for important intellectual content; and final approval of the article.

Acknowledgements

The authors acknowledge Rachel V. Stankowski, PhD of the Marshfield Clinic Research Foundation's Office of Scientific Writing and Publication for assistance in preparing this manuscript.

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Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.
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In children, acute recurrent pancreatitis is attributed to pancreato-biliary anomalies, hereditary pancreatitis and cystic fibrosis. Pancreatic divisum is a common congenital ductal anomaly that leads to recurrence of pancreatitis.
A 13 years old female presented with clinical features of acute recurrent pancreatitis. After ruling out common causes, magnetic resonance cholangiopancreatography was done which showed pancreatic divisum. Her symptoms resolved following duodenum preserving pancreatic head resection.
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Citation Excerpt :
High-quality studies supporting endoscopic therapy in patients with PD and RAP are lacking. In aggregate, data from retrospective uncontrolled studies suggest that endoscopic intervention may reduce or eliminate episodes of RAP in up to 60%–80% of patients.24 However, these results should be interpreted with caution, given the observational nature of the data, heterogeneity in patient populations, differences in outcome definitions, varied endoscopic interventions, and short follow-up.
The purpose of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide practical, evidence-based guidance to clinicians regarding the role of endoscopy for recurrent acute and chronic pancreatitis.
This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide guidance on a topic of clinical importance to the AGA membership, underwent internal peer review by the Clinical Practice Updates Committee (CPUC), and external peer review through standard procedures of Gastroenterology. This review is framed around the 8 best practice advice points agreed upon by the authors, based on the results of randomized controlled trials, observational studies, systematic reviews and meta-analyses, as well expert consensus in this field.
Best Practice Advice Statements
After an unrevealing initial evaluation, endoscopic ultrasound is the preferred diagnostic test for unexplained acute and recurrent pancreatitis. Magnetic resonance imaging with contrast and cholangiopancreatography is a reasonable complementary or alternative test to endoscopic ultrasound, based on local expertise and availability.
The role of endoscopic retrograde cholangiopancreatography (ERCP) for reducing the frequency of acute pancreatitis episodes in patients with pancreas divisum is controversial, but minor papilla endotherapy may be considered, particularly for those with objective signs of outflow obstruction, such as a dilated dorsal pancreatic duct and/or santorinicele. There is no role for ERCP to treat pain alone in patients with pancreas divisum.
The role of ERCP for reducing the frequency of pancreatitis episodes in patients with unexplained recurrent acute pancreatitis and standard pancreatic ductal anatomy is controversial and should only be considered after a comprehensive discussion of the uncertain benefits and potentially severe procedure-related adverse events. When pursued, ERCP with biliary sphincterotomy alone may be preferable to dual sphincterotomy.
Surgical intervention should be considered over endoscopic therapy for long-term treatment of patients with painful obstructive chronic pancreatitis. Endoscopic intervention is a reasonable alternative to surgery for suboptimal operative candidates or those who favor a less invasive approach, assuming they are clearly informed that the best practice advice primarily favors surgery.
When ERCP is pursued, small (≤5mm) main pancreatic duct stones can be treated with pancreatography and conventional stone extraction maneuvers. For larger stones, extracorporeal shockwave lithotripsy and/or pancreatoscopy with intraductal lithotripsy may be required.
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Retrospective cohort of patients with recurrent acute pancreatitis (≥2 episodes) and negative conventional testing. All patients had ≥1 episode after cholecystectomy and completed genetic testing. Primary outcomes were chronic pancreatitis incidence, pancreatic cancer, and mortality. Secondary outcomes included opioid and ERCP utilization.
128 patients met criteria for presumed IRAP. 35 patients met criteria for true IRAP. 12 patients had recurrent acute pancreatitis with gene mutations. Chronic pancreatitis developed in 27 (77.1%) IRAP patients over a median of 6 years. Chronic pancreatitis incidence was similar in IRAP and CFTR mutation carriers; but developed later in SPINK1 carriers. No patients developed pancreatic cancer or died from pancreatic-related causes. Patients were frequently treated with oral opioids and ERCP, without significant differences within or between groups.
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^☆: Part of the data in this manuscript was presented as a poster presentation at Digestive Disease Week, Orlando, FL, May 2013.

¹: Current affiliation: ABQ Health Partners Gastroenterology, 5400 Gibson Blvd SE, Albuquerque, NM, USA.

View full text

Review articleEndotherapy in symptomatic pancreas divisum: A systematic review☆

Abstract

Introduction

Section snippets

Study selection

Literature search

Results

Discussion

Funding support

Disclosure statement

Author contributions

Acknowledgements

Gastrointest Endosc

Gastrointest Endosc

Pancreatology

Gastroenterology

Gastroinstest Endosc

Am J Gastroenterol

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastroenterol Clin North Am

A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum

Endoscopy

Pancreas divisum: incidence and clinical evaluation in Thai patients

J Med Assoc Thai

Proposed nomenclature and classification of the human pancreatic ducts and duodenal papillae. Study based on 100 post mortems

Int Surg

Therapeutic pancreatic endoscopy

Endoscopy

Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations

Am J Gastroenterol

Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis

N Engl J Med

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis

N Engl J Med

Review article
Endotherapy in symptomatic pancreas divisum: A systematic review☆