Pancreas divisum stems from the incomplete fusion of ventral and dorsal pancreas during embryonic development, with consequent changes in the anatomy of the pancreatic duct. In the majority of cases, it is asymptomatic, while its correlation with pancreatitis remains controversial.
Pancreas divisum is diagnosed incidentally in the vast majority of patients because it rarely causes symptoms . Individuals most commonly complain of abdominal pain that may be recurrent, usually in the epigastric and periumbilical region. In rare cases, severe abdominal pain can be related to the development of pancreatitis, since certain studies have brought pancreas divisum into connection with the development of idiopathic pancreatitis.
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Up to 53% of patients with PD and IP have underlying idiopathic chronic pancreatitis (CP), and in rigorous prospective clinical follow-up and/or natural history studies, many with idiopathic recurrent acute pancreatitis (IRAP) have idiopathic CP. [ncbi.nlm.nih.gov]
Comparative studies with rigorous methodology are needed. [annalsgastro.gr]
The diagnosis of pancreas divisum mandates the use of specific imaging procedures, as conventional techniques, including plain radiography, computed tomography (CT) and even plain magnetic resonance imaging (MRI) are not able to identify this pancreatic anomaly .
Although endoscopic retrograde cholangiopancreatography is an invasive diagnostic technique that requires insertion of an endoscope into the duodenum, it is the optimal diagnostic procedure in differentiating pancreatic pathology. Through this method, a direct view into the dorsal and ventral ducts may be obtained, through the accessory and major papilla, respectively. In addition to ERCP, magnetic resonance cholangiopancreatography (MRCP) is becoming increasingly used in practice, because it is noninvasive while showing equally good results . Endoscopic ultrasonography has also shown to be useful in diagnosing pancreas divisum . ERCP and MRCP are, however, the gold standard in differentiating pancreas divisum from other pancreatic conditions, including pseudocysts, malignancies, and inflammatory changes.
Asymptomatic patients require no treatment, as the condition itself does not pose a threat. If pancreatic secretions reach the duodenum without delay through the accessory papilla, then the pancreas is able to exert its functions regardless of its incomplete fusion. In patients who experience mild symptoms, conservative therapy consisting of analgesics, primary non-steroidal anti-inflammatory drugs (NSAIDs) and observation can be instated, as complications are very rare. However, in the case of papillary stenosis, or in patients with significant and recurrent symptoms, surgical treatment may be necessary to facilitate normal pancreatic outflow. Depending on the severity of the condition, various treatment modalities exist . Endoscopic therapy is used in virtually all cases and includes various techniques. Sphincterotomy, sphincteroplasty, stent insertion or plain dilation of the minor papilla are all used in patients with pancreas divisum to alleviate symptoms, but rates of symptom resolution after surgical therapy are variable . In fact, certain studies have evaluated the use of open surgery versus endoscopic therapy in patients with chronic pancreatitis in the setting of pancreas divisum . Various complications after either treatment modality can occur, such as restenosis of the accessory papilla, stent migration, and recurrence of symptoms, which is why treatment, in general, should be carefully evaluated in patients with this condition, as it may cause more harm than benefit.
Because the majority of patients are asymptomatic, this condition has a good prognosis, but its role in patients with pancreatitis remains to be established. It is still not fully proven that surgical therapy proves a benefit to patients with pancreas divisum , since symptoms are known to recur despite treatment. But in general, this condition doesn't pose a significant risk for the patient.
During organogenesis, the pancreas is formed by the fusion of two pancreatic anlagen - dorsal and ventral. The failure of fusion leads to changes in the anatomy of pancreatic duct . It is not known which factors trigger this embryonic malformation. Increased presence of mutations in cystic fibrosis transmembrane conductance regulator(CTFR) gene is noticed in patients, but their role in the development of pancreas divisum remains to be elucidated .
Although pancreas divisum is considered to be the most common congenital variant in humans , its occurrence is considered to be rare. Global prevalence rates are currently not established. Older studies have established a prevalence rate of about 7% on post-mortem examinations , while the most recent systematic review established an overall prevalence rate of around 3% on more than 30 000 individuals . This study has shown significant variations across different parts of the world, with 1.5% prevalence rates in Asia, 5.7% in the United States and 6% in Europe . The patients with CTFR associated pancreatitis have a high chance of developing PD . Having these data in mind, the current theory suggests that a combination of genetic factors and this embryonic anomaly contributes to the development of pancreatitis .
Under physiological conditions, the pancreatic duct travels from the tail, through the body and the anterior part of the pancreatic head (which are formed of the dorsal anlagen), eventually descending into the posterior pancreatic head (belonging to the ventral part). It terminates at the major papilla of the duodenum, where pancreatic juices are released into the gastrointestinal tract to aid in digestion. In pancreas divisum, the pancreas is not uniform, and the posterior head of the pancreas is not connected to the rest of the organ. As a result, pancreatic juices enter the duodenum through the pancreatic duct that terminates in the accessory papilla, which is much smaller in diameter and more prone to structural changes that may lead to obstruction . There are anatomical variations of pancreas divisum, in some cases, the complete ductal system drains through minor papilla.
As the process of fusion of the two pancreatic parts occurs during early organogenesis without a known pathophysiologic mechanisms, prevention strategies currently do not exist. This condition is relatively benign, however, and specific preventive measures may not be of significant benefit, since the diagnosis is often made incidentally during workup for other pancreatic or abdominal diseases.
Pancreas divisum is the most common pancreatic embryonic anomaly and comprises a failure of fusion of ventral and dorsal pancreatic ducts during organogenesis . The two main parts of the pancreas, ventral and dorsal anlagen, fail to fuse around the 6th week of fetal development, which leads to significant changes in normal pancreatic juice flow . The pancreatic duct, which should normally travel from the tail into the ventral part of the pancreatic head and drain into the major papilla, does not descend but drains into the minor papilla, while a small portion of the duct in the ventral pancreas drains into the major papilla. Because of the structural changes, numerous studies have attempted to correlate this anomaly with increased rates of pancreatitis, but the theory remains to be solidified. In patients that do have recurrent bouts of acute pancreatitis, cystic fibrosis genes, primarily the cystic fibrosis transmembrane conductance regulator (CFTR) gene has shown increased expression in these patients, which suggests that other factors also play a role in developing complications from this anomaly . This condition is considered to be rare, but certain studies established a prevalence rate of about 7% in post-mortem examinations . The majority of patients with pancreas divisum are asymptomatic, with the most common complaint being abdominal pain. The diagnosis can be made by both noninvasive and invasive imaging procedures. Endoscopic retrograde cholangiopancreatography (ERCP) is more commonly described as the tool with which the diagnosis is made, primarily because the majority of cases are discovered incidentally during this examination. Magnetic resonance cholangiopancreatography (MRCP) together with secretin stimulation is a noninvasive but equally specific diagnostic method that can be used to confirm the diagnosis . As the majority of patients do not have complaints, treatment often includes observation only, while those with minimal symptoms can be treated conservatively with analgesics. In cases where papillary stenosis or obstruction of pancreatic juice flow is discovered, surgical treatment is indicated. Dilation of the accessory papilla, partial papillotomy, stenting or sphincterotomy may be performed, usually through laparoscopy.
Pancreas divisum is a term that describes a rare congenital abnormality which is characterized by the incomplete formation of the pancreas during early fetal life. In this condition, instead of a single, uniform duct, there are two ducts - dorsal and ventral. This condition is benign and asymptomatic in the vast majority of patients, but its clinical significance stems from the fact that the pancreas drains through a much smaller opening in the duodenum, which may cause impaired pancreatic juice flow and stasis. Its connection with pancreatitis, however, remains to be solidified, as conflicting results are obtained regarding its correlation with inflammatory diseases of this organ. The cause, as well as the mechanism of how this congenital anomaly occurs, remains unknown, but a significant link between mutations in CTFR genes and this malformation has been made. Pancreas divisum is diagnosed incidentally in virtually all patients, with a very rare occurrence of symptoms. When symptoms are present, abdominal pain is most commonly reported. Pain is usually reported in the area around the navel area and below the ribs and can be recurrent. The diagnosis can be made by somewhat specific imaging techniques, such as endoscopic retrograde cholangiopancreatography (ERCP), which is an invasive method that includes insertion of an endoscope into the duodenum. However, it provides a direct view of the orifice through which the pancreas should drain, as well as the ductal system. Magnetic resonance cholangiopancreatography (MRCP) is becoming more frequently used in medical practice because it is noninvasive and includes insertion of contrast that identifies the presence of malformed pancreatic ducts. Treatment is rarely indicated and usually consists of administration of non-steroidal anti-inflammatory drugs (NSAIDs) to alleviate pain. In very rare cases, narrowing of the orifice through which the pancreas should drain can be surgically corrected, mainly by endoscopic measures. In general, this condition is benign and poses little risk for the patient, with many individuals being diagnosed with this condition during follow-up for other conditions.
- Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
- Gelrud A, Sheth S, Banerjee S, et al. Analysis of cystic fibrosis gene product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis. Am J Gastroenterol. 2004;99:1557.
- Smanio T. Proposed nomenclature and classification of the human pancreatic ducts and duodenal papillae. Study based on 200 post mortems. Int Surg 1969;52:125.
- Matos C, Metens T, Devière J, et al. Pancreas divisum: evaluation with secretin-enhanced magnetic resonance cholangiopancreatography. Gastrointest Endosc. 2001;53:728.
- Savides TJ, Gress FG, Zaidi SA, et al. Detection of embryologic ventral pancreatic parenchyma with endoscopic ultrasound. Gastrointest Endosc. 1996;43:14.
- Choudari CP, Imperiale TF, Sherman S, Fogel E, Lehman GA. Risk of pancreatitis with mutation of the cystic fibrosis gene. Am J Gastroenterol. 2004;99(7):1358-63.
- Schneider L, Müller E, Hinz U, Grenacher L, Büchler MW, Werner J. Pancreas divisum: a differentiated surgical approach in symptomatic patients. World J Surg. 2011;35(6):1360-1366.
- Liao Z, Gao R, Wang W, et al. A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum. Endoscopy. 2009;41(5):439–444.
- Bertin C, Pelletier AL, Vullierme MP, et al. Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations. Am J Gastroenterol. 2012;107:311–317.
- Fogel EL, Toth TG, Lehman GA, et al. Does endoscopic therapy favorably affect the outcome of patients who have recurrent acute pancreatitis and pancreas divisum? Pancreas. 2007;34(1):21–45.
- DiMagno MJ, Wamsteker E-J. Pancreas Divisum. Current gastroenterology reports. 2011;13(2):150-156.
- Asayama Y, Fang W, Stolpen A, Kuehn D. Detectability of pancreas divisum in patients with acute pancreatitis on multi-detector row computed tomography. Emerg Radiol. 2012 Apr. 19(2):121-125.
- Chalazonitis NA, Lachanis BS, Laspas F, et al. Pancreas divisum: magnetic resonance cholangiopancreatography findings. Singapore Med J. 2008;49(11):951-954.
- Bhutani MS, Hoffman BJ, Hawes RH. Diagnosis of pancreas divisum by endoscopic ultrasonography. Endoscopy. 1999;31(2):167-9
- Avula H, Sherman S. What is the role of endotherapy in chronic pancreatitis? Therapeutic Advances in Gastroenterology. 2010;3(6):367-382.
- Rustagi T, Golioto M. Diagnosis and therapy of pancreas divisum by ERCP: A single center experience. J Dig Dis. 2013;14(2):93-9.