Pancreatic Divisum

Pancreas divisum, in which the dorsal and ventral pancreatic ducts fail to fuse, is the most common congenital anomaly of the pancreas[1] as well as the most common anatomic variation of the pancreatic duct system.[2, 3] It occurs in approximately 7% of autopsy series (range, 1%-14%). The frequency of finding this condition varies greatly in endoscopic retrograde cholangiopancreatography (ERCP) series (4%-25%), depending on the population studied and the degree to which a complete pancreatogram is obtained.

Pancreas divisum develops prenatally. It is caused by the failure of the ducts of the dorsal and ventral buds to fuse during embryologic development, at approximately the eighth week of intrauterine life. In more than 90% of individuals, the proximal one third of the dorsal pancreatic duct regresses as it fuses with the ventral duct, forming the main pancreatic duct.[4]

In the remainder, one of the following occurs. In cases of classic pancreas divisum, the small ventral duct, or duct of Wirsung, drains via the major papilla and the large dorsal duct, or duct of Santorini, drains via minor papilla. Cases of incomplete pancreas divisum are the same as classic divisum, except a small branch connects the ventral and dorsal pancreas. In cases of pancreas divisum with nonpatent major papilla, the entire pancreatic ductal system drains via the minor papilla. In cases of reversed pancreas divisum, the small dorsal duct drains via minor papilla and the large ventral duct drains via major ampulla. This variant has no physiologic significance except in rare cases of pancreatic cancer that do not involve the main pancreatic duct.

Rarely, doubled pancreatic ducts may be formed, as in a 2018 case report.[4]

Symptoms of pancreatic divisum probably are due to the high intrapancreatic dorsal ductal pressure caused by resistance to pancreatic secretion by a small minor papilla orifice. Possible alternate mechanism is intermittent obstruction of drainage by minor papilla proteinaceous plugs.[5] CFTR gene mutation has been found in some cases of pancreas divisum and may be responsible for variations in the occurrences of symptoms.[6, 7, 8, 9, 10]

United States data

Pancreas divisum occurs in approximately 7% of autopsy series (range, 1%-14%). The frequency of finding this condition varies greatly in endoscopic retrograde cholangiopancreatography (ERCP) series (4%-25%), depending on the population studied and the degree to which complete pancreatography is obtained. Pancreas divisum has geographic variations and is found in approximately 4%-10% of the white population and 1%-2% of the Asian population.[11, 12, 13] Geographic variation could be secondary to the diagnostic procedure used.

History

Pancreas divisum usually is a coincidental finding, and most individuals with this anomaly are asymptomatic.

It can be of clinical relevance in the following situations:

• At endoscopic retrograde cholangiopancreatography (ERCP), the small ventral duct must be differentiated from various causes of main pancreatic duct cutoff, such as pancreatic cancer and pancreatic pseudocysts.

• Dorsal pancreatic duct diseases can be missed because only the ventral portion of the pancreas can be viewed via standard major papilla cannulation.

• Patients with symptomatic pancreas divisum present with pancreatitis or chronic abdominal pain. Pancreatitis can be acute recurrent pancreatitis or chronic pancreatitis. Patients with chronic abdominal pain can have a pain syndrome consistent with pancreatitis without an identifiable etiologic cause for pain (serum amylase, lipase, and imaging findings are normal).

Physical examination

The findings from an abdominal examination usually are normal. Epigastric tenderness and a palpable pseudocyst might be present during episodes of pancreatitis.

Computed tomography (CT) scanning and ultrasonography of the abdomen are not sensitive enough to aid in diagnosing pancreas divisum.[14, 15] However, they can detect dorsal duct dilatation and other changes of chronic pancreatitis.

Magnetic resonance cholangiopancreatography (MRCP) is being used with increasing frequency as a noninvasive alternative to diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in the evaluation of the pancreatic duct and various pathologic conditions of the pancreas, including pancreas divisum.[16, 17, 18] Maximum-intensity projection images from MRCP appear to best illustrate the “crossing duct” sign, in which the dominant dorsal duct crosses the intrapancreatic common bile duct to empty into the minor papilla.[2]

In a systematic review and meta-analysis comparing endoscopic ultrasonography (EUS) with MRCP in idiopathic acute pancreatitis, EUS was more diagnostically accurate than MRCP (64% vs 34%), but MRCP after secretin stimulation (S-MRCP) was superior (12%) to MRCP alone (2%) as well as to EUS (2%) in diagnosing pancreatic divisum.[19] The investigators indicated that EUS should be the preferred study for identifying a potential biliary condition and diagnosis of chronic pancreatitis and that S-MRCP can be helpful in identifying a potential anatomic alteration in the biliopancreatic duct system.

Pancreatography

Pancreas divisum is diagnosed by the aid of pancreatography.

Upon endoscopic retrograde cholangiopancreatography (ERCP), the major papilla is often difficult to cannulate, and the duct of Wirsung (ventral duct, see the following image) appears shortened and of small diameter (like a cutoff of the duct) with rapid filling of small accessory ducts.

This should not be confused with a mass lesion such as a malignancy or pancreatic pseudocyst.

At this point, the accessory papilla should be cannulated. A variety of maneuvers have been used to facilitate cannulation. These include simple maneuvers, such as using the long scope position and accessories to include a taper cannula, slick wires, secretagogues, such as sincalide or secretin, and the application of vital dyes.

This should reveal the duct of Santorini (dorsal duct, as shown in the image below) running the entire length of the pancreas.

In symptomatic patients with recurrent episodes of pancreatitis, ERCP may reveal changes in the pancreatic duct characteristic of chronic pancreatitis.

Endoscopic ultrasonography

Endoscopic ultrasonography may be helpful in the identification of pancreas divisum by revealing the absence of a "stalk sign," where the bile duct and pancreatic duct can be seen to run parallel through the pancreatic head.[20]

Manometry

Manometry of the minor papilla is performed infrequently. Symptomatic patients with high basal sphincter pressures might benefit from endoscopic or surgical interventions. However, more studies are needed in this area.

Because the anomaly of pancreatic divisum usually is asymptomatic, treatment is generally offered to symptomatic patients after conducting a complete workup for other causes of pancreatitis and abdominal pain.

Patients with mild symptoms can be managed conservatively. Alternatively, patients with recurrent episodes of pancreatitis or chronic pain may need intervention, which can be performed endoscopically or surgically, to alleviate papillary stenosis. Endoscopic interventions include minor papilla papillotomy (needle-knife sphincterotomy over a stent or pull-type sphincterotomy), endoscopic stenting, and balloon dilation of the minor papilla.

Minor papilla stenosis causing resistance to the flow of pancreatic secretion can lead to increased intraductal pressure. Pathogenesis of pancreatitis and pain in the abdomen is thought to be secondary to increased minor papilla intraductal pressure and, thus, minor papilla ductal decompression is used for management.

Endoscopic minor papilla sphincterotomy can be performed alone or along with stenting.

Sphincterotomy can be performed using a papillotome to make a 4- to 6-mm incision in the 10- to 12-o'clock position or over a stent used as a guide. Patients may need stent exchange, which is usually performed in 3-12 months, and papillary sphincterotomy is repeated. Postendoscopic minor papilla sphincterotomy pancreatitis and hemorrhage are common complications of endotherapy. Papillary restenosis, stent restenosis, and stent migration[21] can occur after endotherapy.

Lu et al found evidence that endoscopic retrograde cholangiopancreatography (ERCP) is a safe and effective treatment for symptomatic pancreas divisum, with no significant differences between underaged (age ≤17 years) and adult (age ≥18 years) groups in procedures, complications, or long-term follow-up results.[22] In this study, investigators divided symptomatic patients with pancreas divisum (N = 82) into underaged and adult groups, reviewed their clinical information, and contacted them by telephone or reviewed their medical records to determine their long-term follow-up outcomes. After a median follow-up of 41 months, the overall response rate was 62.3%.[22]

In a systematic review on endotherapy and surgery for pancreas divisum, in which complete or partial pain relief was considered as “response” to treatment, the pooled response rate of endotherapy for acute recurrent pancreatitis was 79.2%, 69% for chronic pancreatitis, and 54.4% for patients with pain related to pancreas divisum.[13] The pooled overall response rate to endotherapy was 69.4%, whereas the response rate to surgery was 74.9%; the difference between the two was not significant. Thus, endotherapy can be a reasonable first-line treatment option for pain relief in pancreas divisum.

In a Medline search to identify all studies that compared the outcomes of endoscopic or surgical therapy for pancreas divisum, (56 observational studies: 31 endoscopic studies, 25 surgical studies), Hafezi et al found that, compared with endoscopic treatment, surgery had a higher success rate (72% vs 62.3%), lower complication rate (23.8% vs 31.3%), and lower reintervention rate (14.4% vs 28.3%).[23]

As explained above, acute recurrent pancreatitis had a higher response rate than chronic pancreatitis or chronic abdominal pain associated with pancreas divisum.[13, 24] Rustagi et al found a similar result: a 94% response rate for acute recurrent pancreatitis, 57% for chronic pancreatitis, and 54% for chronic abdominal pain.[25]

All patients selected for surgical treatment should have confirmation of pancreas divisum by endoscopic retrograde cholangiopancreatography (ERCP).

The choice of operation depends on the clinical picture and extent of the disease.[26]

Surgical minor papilla sphincterotomy and sphincteroplasty are discussed as follows:

• Surgical sphincterotomy series and sphincteroplasty series seem to have similar outcomes.

• When patient categorization is detailed, meaning recurrent, acute pancreatitis, chronic pain alone, or chronic pancreatitis is present, patients with recurrent attacks of pancreatitis usually respond better to surgical therapy, mirroring the endoscopic therapy series results.

• In a systematic review, Liao found that the pooled response rate to surgical intervention for acute recurrent pancreatitis, chronic pancreatitis, and chronic abdominal pain was 83.2%, 66.7%, and 51.6%, respectively; the overall response rate to surgery was 74.9%.[13]

• Some studies have found that patients with chronic pancreatitis have better response to surgical procedure than endotherapy.[23]