Development of pancreas

A brief introduction to embryology of pancreas and few developmental anomalies.

1. DEVELOPMENT OF PANCREAS

2. Pancreatic Parenchyma Ductal system Cellular system

3. The pancreatic parenchyma is formed by fudion of two buds. These buds arise from posterior foregut endoderm in the developing embryo. dorsal bud (larger, first) and ventral bud (smaller, later)

4. 4 weeks of gestation

5. 6 weeks of gestation

6. 7 weeks of gestation

7. After the pancreatic buds fuse, the cellular architecture of the pancreas rapidly expands. Notably, all 3 functionally distinct parenchymal cell types—acinar, duct, and islet cells— differentiate from a common pancreatic progenitor lineage

8. primary transition- Predifferentiated cells Protodifferentiated cells low levels of pancreas-specific proteins Alpha cells predominate

9. secondary transition Rise in pancreatic cell number and differentiation high levels of pancreas-specific proteins Beta cells outnumber othercells

10. Development of ductal system

11. Transcription factors and signals for development of pancreas Pancreatic and duodenal homeobox 1 (Pdx1)-

12. Human homeobox gene 9 (Hlxb9)

13. Why we need to know these factors? During recovery from pancreatic injury (e.g., after a bout of acute pancreatitis), several embryonic transcription factors reemerge from within the remaining acinar cells or from new ductular complexes called acinar-to-ductal metaplasia . pancreatic ductal adenocarcinoma and its noninvasive precursor lesion, pancreatic intraepithelial neoplasia ( PanIN ), develop from a similar process of acinar- toductal metaplasia, in addition to forcing the transcription of embryonic genes such as Notch

14. Developmental anomalies of pancreas

15. Annular pancreas is a rare congenital abnormality characterized by a ring of pancreatic tissue surrounding the descending portion of the duodenum.

16. Epidemiology and associations Prevalence -ranges from 5 to 15 per 100,000 adults,in an autopsy series. associations

17. failure of the ventral bud to rotate with the duodenum, causing envelopment of duodenum

18. Theories Approximately one-third to one-half of patients with annular pancreas also have pancreas divisum .

19. •Type I – The annular duct flows directly into the main pancreatic duct •Type II – The duct of Wirsung encircles the duodenum but drains at the major papilla •Type III – The annular duct drains into the common bile duct from the dorsal side •Type IV – The annular duct drains into the common bile duct without the duct of Wirsung •Type V – The annular duct drains into the duct of Santorini from the ventral site •Type VI – The annular duct drains into the duct of Santorini with malfusion

20. Clinical Manifestations There are two peaks of detection. More than two-thirds of children present during the neonatal period. feeding intolerance Vomiting(nonbilious) abdominal distension 

21. Most adults present with symptoms between the ages of 20 and 50 years Other symptoms include upper gastrointestinal bleeding from peptic ulceration, acute or chronic pancreatitis, and, rarely, jaundice due to biliary obstruction. Pain abdomen Post prandial fullness Nausea, vomiting

22. The pathogenesis of pancreatitis in individuals with annular pancreas remains unclear. It is hypothesized that pancreatitis may result from fibrosis leading to partial obstruction of the pancreatic duct in the head of the pancreas. Pancreatic fibrosis in acute pancreatitis is usually limited to the annulus and adjoining pancreatic head, whereas the body and tail are generally spared. Peptic ulcers with annular pancreas are often postbulbar . Obstructive gastrointestinal symptoms result from duodenal obstruction due to scarring from repeated pancreatic inflammation or from peptic ulcer disease. Obstruction of the intrapancreatic portion of the common bile duct due to edema and fibrosis of the pancreatic head can result in obstructive jaundice

23. Diagnosis of annular pancreas should be suspected in infants and children with feeding intolerance, abdominal distension, and vomiting. adults, annular pancreas is usually diagnosed incidentally. Ct scan candiagnose the annular pancreas. endoscopic ultrasound has been used in patients with annular pancreas, its role in the work-up of annular pancreas has not been established

24. In symptomatic neonates, a plain abdominal radiograph will show the classic "double bubble" sign with air in the stomach and duodenum Abdominal CT scan — Abdominal CT scan findings consistent with annular pancreas include descending duodenal narrowing and ring of pancreatic tissue encircling the duodenum. The ring may completely encircle the pancreas or, in patients with incomplete annular pancreas perform a magnetic resonance cholangiopancreatography (MRCP) when the results from upper GI series or abdominal CT findings are equivocal and in patients whose symptoms are unexplained.

25. Management Most patients with annular pancreas are asymptomatic, and thus the presence of annular pancreas does not necessarily indicate that symptoms can be attributed to it surgery remains the procedure of choice in patients in whom symptoms can be attributed to annular pancreas. to relieve duodenal or gastric outlet obstruction by bypassing the annulus. Resection of the annulus should be avoided since it is associated with pancreatitis, pancreatic fistula formation, and incomplete relief of obstruction. In neonates, relief of obstruction is accomplished with a duodenoduodenostomy . In adults, a duodenojejunostomy or gastrojejunostomy is recommended as the duodenum is less mobile. Pancreaticoduodenectomy has been recommended when annular pancreas is associated with obstructive pancreatic duct stones in the setting of chronic pancreatitis or a periampullary lesion that is suspicious for a malignancy

26. Pancreatic divisum the most common congenital pancreatic anomaly Occurs in approximately 10% of population. In one retrospective study consisting of 1825 ERCP, divisum was found in 7.5% cases.

27. Failure of fusion of the ventral and dorsal duct system results in pancreas divisum .

28. Types of pancreatic divisum 1.complete – 70% of all cases of divisum Drains the major papilla Drains the minor papilla

29. Incomplete – 15% a small branch of the ventral duct communicates with the dorsal duct

30. Reverse divisum accessory duct of Santorini does not connect with the genu of the main pancreatic duct

31. Clinicqal manifestations More than 95 percent of patients with pancreas divisum are asymptomatic. Most symptomatic patients have infrequent bouts of pancreatobiliary -type pain or develop mild acute pancreatitis.

32. Pancreatitis in Pancreatic Divisum Controversial as majority of patients are asymptomatic Inadequate drainage Ductal distension pain As the main causative agent is relative stenosis of the minor papilla, this condition has been termed the dominant dorsal duct syndrome

33. associations

34. Diagnosis often diagnosed incidentally on abdominal imaging. should be suspected in patients with idiopathic recurrent acute pancreatitis the imaging modality of choice is MRCP, which demonstrates the failure of fusion of the ventral and dorsal duct system. visualization of the dorsal pancreatic duct crossing anterior to the common bile duct and draining superiorly into the minor papilla and visualization of a separate ventral pancreatic duct.

35. Image of divisum

36. management Incidental finding in asymptomatic patients- no treatment is recommended. Patients with minimal/infrequent symptoms-Conservative management(low fat diet, analgesics, anticholinergics, and if necessary, pancreatic enzyme supplements) Patients with recurrent/severe symptoms -pancreatic imaging ( eg , MRCP) and an evaluation of the underlying etiology minor papilla therapy for patients with two or more bouts of acute pancreatitis regardless of severity, and consider therapy in patients with one bout of severe acute pancreatitis if no other etiology is found

37. Therapy Surgical Vs Endoscopic Surgery is usually reserved for fail endoscopic therapy or in whom endoscopy is not possible. In a systematic review that included 28 studies in which patients underwent endotherapy or surgery for pancreas divisum , there was no significant difference in the proportion of patients with complete or partial pain relief (70 and 75 percent, respectively).

38. Surgical therapy minor papilla sphincterotomy or sphincteroplasty. limited by a morbidity rate of approximately 10 percent. The rate of major complications is approximately 4 percent, and the restenosis rate is approximately 8 percent. Other surgical procedures have been used in selected cases. Patients with obviously dilated dorsal ducts may be candidates for a Puestow procedure (lateral pancreaticojejunostomy ). Severely symptomatic patients who fail to respond to duct decompression, or those with non-dilated ducts who fail to respond to minor papilla or medical therapy, may be candidates for pancreatic denervation or resection, but results from both are variable. Total pancreatectomy has controlled incapacitating pain in a limited number of patients, but severe maldigestion and diabetes mellitus are inevitable complications

39. Endoscopic therapy Endoscopic sphincterotomy. Endoscopic therapy response rates range from 76 to 80 percent in patients with recurrent acute pancreatitis [5,10-12]. Response rates appear to be lower in patients with chronic pancreatitis (42 to 69 percent), and chronic abdominal pain (33 to 54 percent). Pull type sphincterotomy Needle knife sphincterotomy Endoscopic dilation of the narrowed minor papilla and long-term endoscopic stenting are no longer performed for treatment of pancreas divisum due to the risk of associated complications