Pancreas Divisum: The Culprit or an Accomplice in Pancreatitis?

Abstract

Introduction

The true causal relationship between pancreas divisum (PD) and pancreatitis is underexplored. Through this study, we aim to determine the prevalence and type of PD, and its association with idiopathic pancreatitis.

Methods

We retrospectively reviewed all magnetic resonance cholangiopancreatographies (MRCPs) done in our center over 6 months (n = 2,762) for the presence and type of PD, acute or chronic pancreatitis, and any known etiology for pancreatitis. Statistical comparison was made between PD and non-PD groups using chi-square test for various demographic, clinical, and imaging parameters.

Results

PD was seen in 3.5% of MRCPs (98 out of 2,762) of which it was an incidental finding in 39%; 52% had idiopathic pancreatitis and 9% had other risk factor-associated pancreatitis (p < 0.00001). Idiopathic pancreatitis was found in 57.5, 52.5, and 44.5% of cases with type I PD (23/40), type II PD (21/40), and type III PD (8/18), respectively (p = 0.29). PD was demonstrated in 6.2% of patients with idiopathic pancreatitis (51/816) and 2.5% of patients with no pancreatitis (47/1848) (p = 0.0001), suggesting etiological relationship. However, there was no statistically significant difference in occurrence of idiopathic pancreatitis in patients with or without PD (85% vs. 76%, p = 0.5).

Conclusion

Idiopathic pancreatitis is more prevalent in India compared with the West, despite the lower prevalence of PD. There is no difference in occurrence of idiopathic pancreatitis between PD and non-PD groups despite higher prevalence of PD in these patients, suggesting that PD by itself may not act as the sole cause of pancreatitis; it probably increases the susceptibility to idiopathic pancreatitis.

Keywords

pancreas divisum - idiopathic pancreatitis - magnetic resonance cholangiopancreatography - MRCP - recurrent acute pancreatitis

Introduction

Pancreas divisum (PD) is the most common developmental anatomic variant of pancreatic duct, which occurs due to failure of fusion of dorsal and ventral pancreatic anlage in the 6th to 8th week of intrauterine life.[1] Prevalence of PD ranges from 5 to 14% in the general population.[2] Three variants of PD have been described ([Fig. 1]): type I or classical divisum in which there is complete failure of fusion of both dorsal and ventral ducts; type II in which ventral duct is absent; and type III where a small filamentous communication is present between the two ducts.[3] This causes most of the pancreas to drain into the minor papilla through the dorsal duct.[3] Although endoscopic retrograde cholangiopancreatography (ERCP) is the historical gold standard for diagnosing PD, its inherent invasiveness and potential for complications render magnetic resonance cholangiopancreatography (MRCP) to be a compelling diagnostic alternative.[4] MRCP enables a noninvasive diagnosis of PD without the use of intravenous contrast material and avoids the risk of ERCP-induced acute pancreatitis or other complications.[5] Rarely, PD is associated with a focal cystic dilation of the terminal portion of the dorsal duct of Santorini, which is termed as a Santorinicele.[6]

Fig. 1 Illustration depicting types of pancreas divisum.

The clinical significance of PD remains a subject of ongoing debate. Although conventional teaching lists PD as a cause of acute pancreatitis (AP), recurrent AP (RAP), and chronic pancreatitis (CP), this association was based on older studies,[7] [8] [9] which lacked adequate workup to determine the actual cause of pancreatitis. It is likely that many of these so-called idiopathic pancreatitis cases were mistakenly linked to PD, as the actual cause of pancreatitis was not identified or looked for. This conventional wisdom is now being widely questioned as lately other coexisting causes of pancreatitis have been identified in PD patients including genetic mutations (CFTR, SPINK1), which predispose them to pancreatitis independent of the presence of PD.[8] [9] We acknowledge that these genetic studies are not widely available and it may not be practical to perform genetic analysis as a part of etiological workup in all or most of the pancreatitis patients. Through this study, we aim to assess the prevalence of PD in the Indian subcontinent, types of PD, and its association with idiopathic pancreatitis.

Materials and Methods

The current retrospective study was undertaken at a tertiary care hospital after obtaining approval from the Ethics Committee with waiver of consent. We retrospectively reviewed all MRCP studies done in our center over a period of 6 months, from December 2023 to May 2024 (n = 2,762) for the presence of PD, type of PD, and any imaging features of pancreatitis (AP/RAP/CP). The clinical data (including but not limited to symptoms at presentation, prior history of pancreatitis, and laboratory findings) was reviewed for all cases: AP and RAP were grouped into one category, CP into one category, other abdominal pain into one category, and all other unrelated pathologies (like chronic liver disease, liver transplant workup, biliary pathologies, and so on) into one category. In all cases of PD or pancreatitis, electronic medical records (EMRs) were accessed to look for any known etiology that could predispose to pancreatitis (e.g., gallstones, alcohol, ERCP, trauma, hypercalcemia, hypertriglyceridemia, etc.). All the MRCPs were reviewed on our Picture Archiving and Communicating System workstations, together by a fellow in abdominal radiology and a supervising abdominal radiology specialist with 13 years' experience in reading abdominal magnetic resonance imaging scans. Any patient with imaging features suggestive of either acute or definite CP were labeled as pancreatitis in our study even when there is no historical documentation in EMR. Any patient with MRCP showing PD (with or without pancreatitis) was classified into the PD group. We did not review the ERCP in any of these patients. All patients with focal pancreatic head lesions (either malignancy or collections) that can obscure background pancreatic ductal anatomy were excluded from the analysis.

MRCP Imaging Technique

All the examinations were performed on Philips 1.5-Tesla (Ingenia S) or Philips 3-Tesla (Ingenia Elition X) MR scanners without the usage of any intravenous paramagnetic contrast agents. Approximately 75 to 100 mL of dilute iron containing syrup was administered orally prior to the scan, to reduce signal intensity of bowel contents and improve visualization of the pancreaticobiliary tree. [Table 1] lists the MR sequences performed as per the institutional protocol.

Table 1 MRCP sequences

MRI sequences	Section thickness (mm)		Slice gap (mm)		TR/TE		Flip angle		FOV (cm)
	1.5 T	3 T	1.5 T	3 T	1.5 T	3 T	1.5 T	3 T	1.5 T	3 T
T2 FS (MVXD) axial	3.3	3.5	0.8	0	4200/80	2500/80	90°	90°	65 × 35	65 × 35
T2FS coronal	3.5	5	1	1	1000/80	1200/80	90°	90°	50 × 28	50 × 28
3D MRCP coronal	2	1.8	1	0.9	2000/800	1300/600	90°	90°	50 × 28	50 × 28
T2 TSE axial	3.3	3	0.8	0	4100/80	2700/129	90°	90°	65 × 35	65 × 35
DWI	5	6	1	0	2700/80	2500/55	90°	90°	78 × 45	62 × 35
T2 SPI zoom	3.5	3	0	0	2700/70	2500/70	90°	90°	35 × 22	35 × 22
BTFE axial	5	6	0.6	1	3.4/1.7	2.9/1.4	90°	90°	65 × 35	65 × 35
T1 Dixon	4	4	2	2	5.73/2.37 and 4.75	3.5/2.4 and 1.2	10°	10°	65 × 35	65 × 35
Coronal thick slab MRCP	50	50	0	0	8000/800	6100/800	90°	90°	52 × 30	52 × 30

Abbreviations: 3D, three-dimensional; BTFE, balanced turbo-field-echo; FOV, field of view; FS, fat saturation; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; MVXD, MultiVane-XD; SPI, sheet probability index; TR/TE, repetition time/echo time; TSE, turbo spin echo.

Statistical Analysis

Continuous and categorical data were described in terms of range, mean ± standard deviation, frequencies (number of cases), and relative frequencies (percentages) as appropriate. Demographic, clinical, and imaging parameters between the PD and non-PD groups were compared using the chi-square test. A p-value of < 0.05 was considered statistically significant. Data documentation and statistical analysis were performed using Excel (v.2016) and IBM SPSS statistical package version 23.

Results

Comparative demographics and clinical presentation of the PD group and non-PD group are shown in [Table 2]. PD was seen in 3.5% of the MRCPs (98 out of 2,762). Of these 98 patients, PD was an incidental finding in 38 patients (39%) with no clinical or imaging features of pancreatitis; 9 patients (9%) had gallstone or alcohol-induced pancreatitis and the rest 51 patients (52%) had idiopathic pancreatitis (p < 0.00001). The etiology of pancreatitis in PD and non-PD groups is listed in [Table 3]. When analyzed by PD type, 57.5% of patients with type I PD (23/40), 52.5% with type II PD (21/40), and 44.5% with type III PD (8/18) had idiopathic pancreatitis ([Table 4]), which is not statistically significant.

Table 2 Demographic, clinical, and imaging parameters

	Pancreas divisum (n = 98)	No pancreas divisum (n = 2,664)	p-Value
Mean age in years (range)	30 (6–80)	45 (1–86)	0.0001
Gender	Male: 63 (64%) Female: 35 (36%)	Male: 1,880 (70%) Female: 784 (30%)	0.21
Clinical presentation			0.0001
- AP and RAP - CP - Other abdominal pain - Unrelated pathologies	30 (30.6%) 30 (30.6%) 7 (7.1%) 31 (31.7%)	501 (18.8%) 510 (19.1%) 183 (6.9%) 1470 (55.2%)
Clinical/Imaging features of pancreatitis	Present: 60 (61%) Absent: 38 (39%)	Present: 1,011 (38%) Absent: 1,653 (62%)	0.0001
Type of pancreas divisum	Type I: 40 Type II: 40 Type III: 18	–	–

Abbreviations: AP, acute pancreatitis; CP, chronic pancreatitis; RAP, recurrent acute pancreatitis.

Table 3 Etiology of pancreatitis

Etiology	PD (n = 60)	No PD (n = 1,011)	p-Value
Alcohol and biliary	9 (15%)	210 (21%)	0.33
Idiopathic	51 (85%)	765 (76%)	0.50
No etiological information	0	36 (3%)	–

Abbreviation: PD, pancreas divisum.

Table 4 Idiopathic pancreatitis in types of pancreas divisum

Types of pancreas divisum	Idiopathic pancreatitis	Other causes of pancreatitis	No pancreatitis	p-Value
Type I (n = 40)	23 (57.5%)	5 (12.5%)	12 (30%)	0.29
Type II (n = 40)	21 (52.5%)	3 (7.5%)	16 (40%)
Type III (n = 18)	8 (44.5%)	0 (0%)	10 (55.5%)

PD was seen in 6.2% of patients with idiopathic pancreatitis (51/816) while only 2.5% of patients (47/1,848) with normal pancreas (no AP/CP) had PD as an incidental finding (p = 0.0001). These findings suggest a significant association between PD and idiopathic pancreatitis, while also highlighting that a considerable proportion of PD cases remain asymptomatic and can be picked up as an incidental finding on imaging. Three of the PD patients had Santorinicele and two PD patients had associated pancreaticobiliary maljunction and choledochal cyst. Representative MRCP images are depicted in [Figs. 2] [3] [4].

Fig. 2 Dorsal pancreatic duct (yellow arrow) crossing anterior to the common bile duct (CBD) and opening into the minor duodenal papilla; no communication with the ventral pancreatic duct (white arrow), which is draining into major papilla along with CBD—type I pancreas divisum.

Fig. 3 Dorsal pancreatic duct (yellow arrow) crossing anterior to the common bile duct (CBD) and opening into the minor duodenal papilla; absent ventral pancreatic duct—type II pancreas divisum. Bulbous dilatation of dorsal duct at the minor papilla—Santorinicele (curved white arrow).

Fig. 4 Filamentous communication (yellow arrow) between dorsal pancreatic duct and ventral pancreatic duct—type III pancreas divisum.

Discussion

The etiology of AP becomes clear following routine investigations during or after the initial attack in 70 to 80% of patients (45% gallstones, 20–25% alcohol consumption, 5–7% post-ERCP, 5% other reasons).[10] In the rest 20 to 30% of individuals, the etiology of pancreatitis remains unknown following a routine initial evaluation; these patients are labeled as idiopathic pancreatitis. For the purpose of our study, we have also labeled these patients as idiopathic pancreatitis after reasonable exclusion of causes listed above. PD was earlier thought to be the causative factor in a subset of these idiopathic pancreatitis patients based on older studies[7] [11] [12] where there was inadequate workup for potential etiological factors. Recent research has challenged this direct causal link, suggesting that many patients with PD and pancreatitis also carry genetic mutations, such as in the CFTR and SPINK1 genes, that independently predispose them to pancreatitis.[8] [9] _. PD is a common finding with a reported frequency of 3 to 13% in autopsy, MRCP, and ERCP studies.[6] [13] [14] The prevalence of PD is thought to be higher in the Western population (5–10%) compared with the Asian population (1–2%).[11] [15] [16] [17] [18] Our study based on Indian population shows similar prevalence (3.5%) as that of other Asian population studies. This is despite the higher prevalence of idiopathic RAP (20–25%)[10] and idiopathic CP (41%)[19] in India, suggesting that PD cannot be the sole or main etiology in idiopathic pancreatitis cases. There are other proven environmental[20] [21] and genetic factors[8] [9] [21] at play, which are now consistently linked to idiopathic pancreatitis.

Our study found a statistically significant higher prevalence of PD in idiopathic pancreatitis patients compared with the general population (6.2% vs. 2.5%; p-value 0.0001) similar to some of the older studies[22]; however, there is no significant difference in the etiological factors causing pancreatitis in the PD group compared with the non-PD group in our analysis. This also aligns with the idea that while PD increases the susceptibility to idiopathic pancreatitis, it is unlikely to be the primary or only cause in many of these patients. In a large genetic study, Bertin et al reported significantly higher PD frequency in genetic pancreatitis patients (CFTR, SPINK1, PRSS1 groups), especially the CFTR group (47%), compared with idiopathic pancreatitis (5%) and alcoholic pancreatitis (7%) and in controls (7%), suggesting that PD and CFTR gene mutations might be cofactors explaining the occurrence of pancreatitis.[8] Another study showed increased risk of RAP due to PD in patients with rs12338 polymorphism in the cathepsin B gene.[23]

The pathophysiological reason behind PD causing pancreatitis is based on the fact that most of the exocrine pancreatic secretions from the larger dorsal pancreatic anlage drain through the narrow minor papilla, the diameter of which is considered insufficient to provide adequate drainage, leading to a relative (or functional) outflow obstruction and intrapancreatic enzyme activation.[24] This outflow obstruction may sometimes result in Santorinicele,[25] which was found in three PD cases in our study, two of which also had pancreatitis. But the proportion of 39% asymptomatic PD cases in our study also underscores the fact that many individuals with this anatomical variant remain unaffected throughout their lives. It is likely that only a subset of PD cases with increased intraductal pressure are predisposed to pancreatitis and are, therefore, likely to be benefited from endotherapy or surgery,[26] [27] while the majority of PD cases with near-normal intraductal pressures stay asymptomatic. However, at the moment, there are no reliable or established invasive or noninvasive ways to determine the pancreatic ductal pressure routinely in clinical practice. We also did not find any statistically significant difference in the prevalence of idiopathic pancreatitis in patients with each type of PD (p-value 0.29).

In the Indian context, the interplay between genetic predisposition and PD still remains underexplored. Given the diverse genetic backgrounds in the Indian population, future studies are needed to investigate the prevalence of relevant genetic mutations in patients with PD and pancreatitis. Such research could help determine whether PD acts as a primary factor, a predisposing factor, or simply an incidental finding in these patients. One of the main limiting factors in our study is the lack of genetic workup for majority of our cases, this being a retrospective observational study. We believe that this study provides important insights into the prevalence, types, and clinical significance of PD, offering valuable insight into its association with idiopathic pancreatitis. To the best of our knowledge, this is one of the largest studies done from a single institution based on Indian population, which emphasized the interplay between PD and idiopathic pancreatitis.

Conclusion

Our study reveals lower prevalence of PD in the Indian population compared with the West (3.5% vs. 10%) despite higher prevalence of idiopathic RAP and idiopathic CP in India. Although half of the patients with PD had idiopathic pancreatitis, PD by itself is not the sole cause and it probably increases the susceptibility to pancreatitis. Genetic and other environmental factors are likely to play a more important and synergistic role than PD in the pathophysiology of pancreatitis. Prospective studies investigating the genetic landscape and long-term outcomes of patients with PD will provide deeper insights into the true clinical significance of this anatomical variant. It is, however, important to identify PD on imaging, as there is literature suggesting response to surgery and endotherapy in idiopathic RAP patients. Timely therapeutic interventions for symptomatic PD can improve outcomes and reduce the burden of RAP.

Conflict of Interest

None declared.

Acknowledgments

None.

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Publication History

Article published online:
13 May 2025