Peer Reviewed

Case in Point

Symptomatic Pancreas Divisum: Recurrent Acute Pancreatitis in a 23-Year-Old Man

Authors:
John H. Rosenberg, BS; John H. Werner, BS; and Shailendra K. Saxena, MD, PhD

Citation:
Rosenberg JH, Werner JH, Saxena SK. Symptomatic pancreas divisum: recurrent acute pancreatitis in a 23-year-old man. Consultant. 2018;58(10):274-278.


 

A 23-year-old white man presented to the emergency department with nonradiating epigastric abdominal pain accompanied by nausea and vomiting for 2 to 3 days. He rated his pain as 10 of 10 in intensity on admission, and he had several episodes of vomiting prior to arrival. He had had at least 4 episodes of acute pancreatitis in the 18 months prior to admission, all with a similar presentation.

The patient reported occasional social drinking, and he smoked cigarettes. He denied known allergies and took no medication prior to admission. His case was managed symptomatically with intravenous fluids, narcotic analgesia, and antiemetics until his pain had resolved and he could tolerate a regular diet on day 3. The patient was discharged on day 5 to his home with a diagnosis of recurrent acute pancreatitis and was referred to a gastroenterologist for further outpatient workup.

Physical examination. Vital signs at the time of admission were as follows: blood pressure, 131/78 mm Hg; temperature, 36.9°C; pulse, regular at 66 beats/min; and respiratory rate, 20 breaths/min. Auscultation of his abdomen demonstrated decreased bowel sounds, while palpation of his abdomen demonstrated diffuse tenderness, with maximum tenderness located in the epigastric area.

Diagnostic tests. The patient’s laboratory test values on his most recent admission are shown in the accompanying Table, along with the values from subsequent admissions for the same symptom of epigastric pain.

Pancreas divisum table

The gastroenterologist saw the patient for an esophagogastroduodenoscopy 1 month after discharge. A duodenal aspirate was positive for cholesterol crystals, and the etiology of his recurrent acute pancreatitis was thought to be microlithiasis. It was recommended that the patient undergo a laparoscopic cholecystectomy. The results of a computed tomography (CT) scan of the abdomen showed peripancreatic fluid, fat stranding, and fluid extending into the pelvis, all signs suggestive of acute pancreatitis. A laparoscopic cholecystectomy was performed 5 months from the time of the initial hospital admission.

The patient had been abstinent from alcohol for 1 year prior to cholecystectomy, and he did not return to the hospital until 2 years after cholecystectomy, when he presented with 1 day of abdominal pain localized to the epigastric area. The pain radiated to the back and was described as 7 of 10 in intensity. He denied nausea, vomiting, fever, or chills. He reported that the pain was similar to that experienced prior to cholecystectomy.

The gastroenterologist recommended a magnetic resonance cholangiopancreatography (MRCP) scan, which failed to demonstrate any abnormalities. The patient’s pain was addressed by providing bowel rest via nil per os diet, intravenous fluids, and pantoprazole until his pain subsided. He was discharged on high-dose pancrelipase, omeprazole, oxycodone, and tramadol.

The patient underwent endoscopic retrograde cholangiopancreatography (ERCP) 1 month later. Attempts to obtain a pancreatogram through the major papilla using a standard catheter and guide wire failed. A prominent minor papilla was identified. Attempts to cannulate the minor papilla before and after secretin administration using an ERCP catheter failed. No output of pancreatic juice was seen after secretin administration. 

The strong suspicion of pancreas divisum led to a minor papilla precut sphincterotomy. The pancreatic duct was cannulated though the minor papilla, and complete pancreatogram was obtained, the results of which were diagnostic for the presence of pancreas divisum.

The patient had agreed to receive a 3F pancreatic stent rather than a 5F stent. An 8-cm long pancreatic stent was placed over a 0.018-inch diameter guidewire. The minor papilla precut was extended. There was no bleeding during the procedure. No cholangiogram was obtained following the procedure. 

NEXT: Discussion

Discussion

Pancreas divisum is the most common congenital anomaly of the pancreas, with a reported worldwide prevalence of 2.9%.1-4 The prevalence of pancreas divisum in Western countries ranges from 8% to 12.6%, but it is much less prevalent in Asian countries, with a 1% to 2% prevalence, meaning it is much more common in the white population.5

Pathophysiology

The pancreas is formed by the rotation of the ventral pancreatic bud and its subsequent fusion with the dorsal pancreatic bud at the junction of the foregut and midgut (Figure 1).3,6 The ducts in the ventral and dorsal pancreatic buds fuse to form the main pancreatic duct. Failure of the distal portion of the dorsal duct to involute will result in the formation of the accessory duct.3,6 The characteristic anatomy of pancreas divisum is the failure of the dorsal and pancreatic ducts to fuse into 1 duct that drains into the major duodenal papilla (major duct, Wirsung duct).7 Instead, the dorsal pancreatic duct, which drains the dorsal head, tail, and body of the pancreas, communicates with the intestinal lumen through the minor duodenal papilla (minor duct, Santorini duct), and becomes the major drainage route for the pancreas.2,6,8,9 The ventral duct continues to drain through the major duodenal papilla along with the common bile duct.7

Fig 1

Pancreas divisum commonly presents as 2 variations: complete divisum or incomplete divisum. Complete pancreas divisum is described as complete separation or absolute lack of fusion between the dorsal and ventral pancreatic ducts and occurs in 70% of cases.10 Incomplete pancreas accounts for 20% to 25% of cases and is characterized by the existence of a small communicating branch between the dorsal and ventral pancreatic ducts, but with most pancreatic exocrine secretions routed through the minor duodenal papilla (Figure 2).6,10,11 The smaller aperture of the minor duodenal papilla increases resistance to outward flow of pancreatic exocrine secretions and can result in significant back pressure within the pancreas, which may lead to the development of pancreatitis.6

pancreas divisum fig 2

Most patients with symptomatic pancreas divisum are categorized into recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain.1 However, evidence suggests that only 10% of people with pancreas divisum are symptomatic, meaning most people with the condition do not experience any adverse effects from their anomalous anatomy.1,9,12,13 Therefore, the role of pancreas divisum and pancreatitis remains somewhat controversial, since many who have pancreas divisum do not experience any abdominal or pancreatic pain. Instead, pancreas divisum is thought to be a predisposing factor to pancreatitis opposed to a causal factor. Most individuals with pancreas divisum are asymptomatic, and the anomalous anatomy usually is uncovered in symptomatic individuals after investigating other more common causes of pancreatitis such as alcohol consumption and gallstones. Some researchers have described pancreas divisum as an independent risk factor for pancreatitis, specifically associated with recurrent acute pancreatitis, chronic pancreatitis, or chronic abdominal pain.4,5,7,10

Other investigators have also noted the association of pancreas divisum and idiopathic pancreatitis with cystic fibrosis transmembrane conductance regulator gene (CFTR) or serine protease inhibitor, Kazal-type 1 gene (SPINK1) mutations.5,7 Mutations in CFTR may be associated with a predisposition to pancreatitis in patients with pancreas divisum.1 In fact, a recent study suggests that pancreas divisum may not be a sole cause of pancreatitis but act as a cofactor alongside predisposing genetic mutations.14 Approximately 22% of patients with clinical symptoms associated with pancreas divisum have mutations in CFTR.15 One study found that persons with pancreas divisum had a greater risk of other pancreaticobiliary abnormalities such as pancreaticobiliary maljunction, intraductal papillary mucinous neoplasm, pancreaticobiliary cancer, and others.9

It has been suggested that complete pancreas divisum might be a factor that promotes oncogenesis.9 An incidence of 11.1% to 12.5% of pancreatic tumors in the setting of pancreas divisum has been reported, with most being ductal carcinomas and intraductal papillary mucinous neoplasms.11 Invasive ductal carcinomas associated with pancreas divisum usually arise from the dorsal pancreas usually due to chronic pancreatitis. The pathogenesis of intraductal papillary mucinous neoplasm in pancreas divisum warrants further investigation.11 Therefore, if pancreas divisum and pancreatitis is present, genetic testing to investigate an alternative explanation for idiopathic pancreatitis should be explored, because endoscopic repair or treatment under those circumstances may not confer benefit to the patient.7 If mutations are not present, therapy targeted to mitigate the progression into chronic pancreatitis should be considered.

NEXT: Pancreatitis and Pancreas Divisum

Interventional therapy in patients with symptomatic pancreas divisum is aimed at mitigating the progression to chronic pancreatitis. There are 2 types of chronic pancreatitis: chronic relapsing pancreatitis, and established chronic pancreatitis. Chronic relapsing pancreatitis is typified by attacks in patients who do not yet have clinically recognized hallmarks of chronic pancreatitis but who have the pathology of chronic pancreatitis. Established chronic pancreatitis has the clinically recognized hallmarks of chronic pancreatitis with or without relapsing attacks of pain.7 The hallmarks of chronic pancreatitis are repeated attacks of pancreatitis, with eventual destruction of acinar and islet cells progressing to where the acinar cells are too few to evaluate, and enzyme levels decrease leading to steatorrhea, creatorrhea, glycosuria, and hyperglycemia.16 Chronic relapsing pancreatitis was first described in 1946 by Comfort and colleagues, mainly in alcoholic pancreatitis as relapsing pain in the presence of ongoing disease.16

Later, Ammann and colleagues stated that pain quality can distinguish early and late pancreatitis.17 Episodes of relapsing pain characterize the early stage of alcoholic pancreatitis; chronic pain is associated with local complications such as pseudocysts and cholestasis, while complete pain relief occurs in advanced chronic pancreatitis.7 Recurrent acute pancreatitis presents similarly to chronic relapsing pancreatitis; however, DiMagno and DiMagno argue the diagnosis of recurrent acute pancreatitis should be reserved for identifiable causes of acute pancreatitis that do not lead to chronic pancreatitis if the causes (gallstones, hypertriglyceridemia) are treated.7

Patients with chronic pain between episodes may have no evidence of chronic pancreatitis even using the most sensitive tests. Categorization of patients into those with recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain may be artificial.18 The classification of symptomatic pancreas divisum remains controversial, although some studies have associated different outcomes regarding improvement of symptoms based on whether the patient demonstrated recurrent acute pancreatitis, chronic pancreatitis, or chronic abdominal pain.

The role of pancreas divisum in recurrent acute pancreatitis is supported by the fact that minor papilla endotherapy has been followed by clinical improvement in those patients. Gupta and colleagues found pancreas divisum in 10% of patients undergoing MRCP for recurrent acute pancreatitis, which was significantly higher than the frequency of pancreas divisum in patients without any pancreatic disease.19 Patients with chronic pancreatitis demonstrated a similar prevalence of pancreas divisum to those without pancreatic disease. This seems to indicate an association with the development of recurrent acute pancreatitis and pancreas divisum, but this association may not exist between the development of chronic pancreatitis and pancreas divisum. Minor papilla endotherapy is recognized as an effective method for alleviating pain, narcotic use, and readmissions because of recurrent acute pancreatitis and chronic pancreatitis in the setting of pancreas divisum.20

NEXT: Diagnosis

Diagnosis

ERCP is the gold standard for diagnosing pancreas divisum because of its ability to visualize the anomalous anatomy as well as contribute a therapeutic effect by relieving pain and slowing the progression to chronic pancreatitis through a sphincterotomy or stenting the papilla.9,13 Pancreas divisum may be confirmed via cannulation of the minor duodenal papilla and dorsal pancreatography; however, cannulation of the minor papilla in pancreas divisum carries the risk of severe pancreatitis.6,13 MRCP for pancreas divisum performed with secretin stimulation has been shown to yield a significant diagnostic advantage. One meta-analysis demonstrated that secretin stimulated MRCP (S-MRCP) yielded a much higher overall sensitivity, and diagnostic odds ratio when compared with MRCP.21

Evidence of pancreas divisum on MRCP can be demonstrated by the common bile duct and dorsal pancreatic duct draining through 2 different duodenal apertures; where the dorsal pancreatic duct will drain through the minor duodenal papilla with no communication with the common bile duct.2 Recent studies have used secretin-stimulated MRCP (S-MRCP) to improve the accuracy and image quality.12 S-MRCP is noninvasive, has good sensitivity and specificity for the evaluation of pancreas divisum, and is not associated with a risk of pancreatitis, unlike ERCP.13 S-MRCP is the first-line imaging modality in diagnosing pancreas divisum due to its sensitivity and safety profile. However, it is more difficult to detect pancreas divisum in the setting of chronic pancreatitis by secretin stimulation due to a poorer-than-average secretin response and the presence of stones or strictures in either the ventral or dorsal pancreatic ducts.21

Endoscopic ultrasonography (EUS) has been used in the diagnosis of pancreas divisum. Absence of the “stack sign,” which normally shows the common bile duct, pancreatic duct, and portal vein, has been suggested as criterion for diagnosing pancreas divisum.13 Studies comparing EUS and MRCP in diagnosing pancreas divisum have had mixed results.13 Some have shown that MRCP has higher sensitivity and specificity, while others have demonstrated the opposite. EUS is more of an operator-dependent imaging modality, and it may not be possible to identify the ventral and dorsal ducts in all patients.13 Objective EUS criteria optimized for diagnosis of pancreas divisum must be defined. Additional studies comparing EUS to other modalities such as MRCP and ERCP are important to determine the role of EUS in diagnosis and predicting therapy response.13 While a promising investigative method, EUS remains in its infancy for use in pancreas divisum.

NEXT: Management

Management

Treatment of symptomatic pancreas divisum is traditionally endotherapy with stenting and/or sphincterotomies. Patients with minimal symptoms may be treated with standard medical therapy (low-fat diet, analgesia, pancreatic enzymes, etc), those with recurrent acute pancreatitis represent the best candidates for endotherapy in pancreas divisum with a predicted sustained response rate of approximately 75%.6 Those with chronic pancreatitis are associated with a 40% to 60% sustained response rate, and those with chronic abdominal pain respond poorly (20%-40%).6

Evidence is accumulating that pancreatic sphincterotomies are useful in some settings for treating pancreas divisum, with some studies showing a success rate of more than 90% in adolescents.12 The efficacy of surgery compared with endotherapy remains controversial in the treatment of symptomatic pancreas divisum. One review compared the efficacy of endotherapy and surgery for pancreas divisum.22 No statistically significant difference in the response rates was found, and the review concluded that endotherapy is a reasonable first-line therapy for pancreas divisum. Endotherapy has been most likely to be effective at reducing the recurrence of recurrent acute pancreatitis, but less than half of patients with pancreas divisum and chronic pancreatitis or chronic abdominal pain are likely to experience a significant reduction in symptoms from endotherapy.1 However, a systematic review and quantitative analysis showed that symptom improvement with surgery was achieved to a significantly higher degree than endoscopy (72% vs 62.3% respectively), and endoscopy was associated with a higher concentration rate than surgery (31.3% vs 23.8% respectively).5 However, no clinical trial or study currently exists comparing symptom reduction in pancreas divisum via surgery or endoscopic therapy.5 Given the lower rate of beneficial outcomes for endotherapy in chronic pancreatitis or chronic abdominal pain, other treatment options such as surgery or radiologic involvement may produce better outcomes.

Conclusion

Pancreas divisum is the most common congenital anatomic anomaly of the pancreas and has the highest prevalence among the white population. Pancreas divisum occurs when the dorsal and ventral pancreatic ducts fail to fuse embryologically in week 8 of development, and the individual is left without any communication between the 2 ducts (complete divisum) or a small branch connecting the 2 ducts (incomplete divisum). Those born with pancreas divisum are usually asymptomatic, while fewer than 10% experience symptomatic pancreas divisum. Symptomatic pancreas divisum has been associated with recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain. Controversy remains about whether pancreas divisum is a causal factor or a predisposing factor to pancreatitis, but recent studies increasingly suggest that pancreas divisum is a predisposing factor to pancreatitis, especially in patients with mutations in CFTR or SPINK1.

Should a patient present with the signs, symptoms, and laboratory test results suggesting pancreatitis, alcohol, gallstones, and hypercalcemia and hypertriglyceridemia should be excluded prior to investigating for a mechanical obstruction such as pancreas divisum. The first-line imaging modality for suspected pancreas divisum is S-MRCP followed by ERCP for possible stenting or sphincterotomy. The aim of treatment in symptomatic pancreas divisum is to mitigate the progression to chronic pancreatitis. Endotherapy has not been shown to have as strong benefit in chronic pancreatitis, so other surgical or radiologic interventions may be more appropriate. n

John H. Rosenberg, BS, is a third-year medical student at the Creighton University School of Medicine in Omaha, Nebraska.

John H. Werner, BS, is a third-year medical student at the Creighton University School of Medicine in Omaha, Nebraska.

Shailendra K. Saxena, MD, PhD, is a professor in the Department of Family Medicine at the Creighton University School of Medicine in Omaha, Nebraska.

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