Recurrent Idiopathic Pancreatitis

1. Recurrent Idiopathic Pancreatitis Rebecca Byers, MD Primary Care Conference June 9, 2004

2. Objectives • Review the common clinical presentation of chronic pancreatitis. • Describe the natural course of chronic pancreatitis. • Discuss the various types of cystic lesions in the pancreas. • Describe the diagnostic and treatment recommendations • Disclaimer - I have not received any outside funding in regards to this presentation.

3. Clinical Case • First Visit – 49 y.o. woman presented to Middleton Hills for an urgent care problem (painful sebaceous cyst). • Focused review of her PMH included a report of: recurrent idiopathic pancreatitis (?due to Dyazide), pseudocyst, normal ERCP-1995; cholecystectomy-earlier in 1995; asthma; TAH/RSO; hypothyroidism; hypercholesterolemia; allergies (PCN, Sulfa, animals).

4. Case • 4/10/98 – Acute onset abdominal pain. Prevacid. Pain resolved. • 7/15/98 - Changed to UW East (closer to her home); concern – BP 180/120; Verapamil started. • 8/18/98 – Patient had stopped med due to hand/foot swelling; Atenolol started. • 9/24/98 - BP 140/100. Migraine headache; Atenolol increased and Imitrex effective.

5. Case • 4/10/98 – Acute onset abdominal pain. Prevacid. Pain resolved. • 7/15/98 - Changed to UW East (closer to her home); concern – BP 180/120; Verapamil started. • 8/18/98 – Patient had stopped med due to hand/foot swelling; Atenolol started. • 9/24/98 - BP 140/100. Migraine headache; Atenolol increased and Imitrex effective.

6. Case • 10/22/98 – BP 140/104; Cozaar added. • I began seeing patient and continued trying to control her BP over the next year. • 10/13/99 – BP 148/90. ETT 9/28/99 normal. • 3/28/00 – BP 150/80 home, 170/108 clinic; ordered echo and renal arteriogram. • 3/30/00 – Hospitalized with acute onset abdominal pain with lipase 7008, amylase 1126; chem 7 and LFTs wnl.

7. Hospitalization 3/30 – 4/4/00 • Stopped Lasix, Lisinopril, Cozaar. • Renal arteriogram – normal. • Echo – normal. • +H. pylori – treated with 2 weeks Biaxin, Flagyl, Prevacid. • Discharged on Amlodipine and Atenolol. • BPs never high since.

8. Hospitalization 6/13 – 6/18/03 • 2/19/01 - 10 minutes 8/10 epigastric pain; next day, normal exam and labs. • 6/13/03 – Acute epigastric pain with radiation to her back woke her from sleep. Lipase elevated, other labs normal. • Abd CT with contrast – evidence of acute pancreatitis and a 5 cm fluid collection near the tail with defined wall and internal septation consistent with pancreatic pseudocyst. ERCP to be done as outpt.

9. GI Clinic Follow-up 6/23/03 • Diagnosis of Recurrent Idiopathic Pancreatitis and a mature pancreatic pseudocyst. • Need to assess for structural abnormality • Plan for repeat CT in 6 weeks and ERCP and/or endoscopic ultrasound. • 8/4/03 – Abd CT without change. 4 non-specific pulm nodules, 6-7 mm. Endless f/u.

10. Hospitalization 12/19-12/24/03 • Sudden onset epigastric pain, lipase 7749. • Recommend follow-up with Surgery regarding probable surgical management of her pancreatic pseudocyst.

11. Hospitalization 1/2 - 1/9/04 • Acute epigastric pain, Lipase 8274, normal LFTs. • ERPC 1/7/04 Impression: 1) Changes consistent with chronic pancreatitis (pancreatic duct with irregularity and narrowing in the mid to distal aspect and some abnormal side branches consistent with chronic pancreatitis 2) Filling of pseudocyst 3) Normal biliary tree 4) Empiric sphincterotomy performed.

12. Hospitalization 2/12 – 2/14/04 • Pain, ……

13. Surgical Consult 2/17/04 • Diagnosis of acute relapsing pancreatitis. • Recommendation for resective drainage operation and definitive treatment.

14. ERPC 2/19/04 • Impression: (1)Recurrent pancreatitis (2) Improved pancreatogram with diffuse pancreatic ductal irregularities less prominent on this exam (3) No definite pancreatic duct stricture(s) visualized (4) s/p 5 mm pancreatic sphincterotomy with prompt drainage of contrast.

15. Endoscopic Ultrasound 3/25/04 • Impression: 1) Pancreatic tail solid-cystic lesion 2) FNA consistent with a mucinous neoplasm. • FNA Report - Cytologic Exam: Positive, compatible with a mucinous neoplasm.

16. Hospitalization 4/4 – 4/22/04 • Acute abdominal pain and fevers (up to 104), secondary to bleed post biopsy. • Surgery Consult 4/6/04 – Recommend a distal pancreatectomy and splenectomy. Vaccinated with H. flu, Meningovax, and Pneumovax. • Concurrent concerns – pulmonary nodules, left-sided pleural effusion, perisplenic fluid collection.

17. Surgery 5/12/04 • Surg Path Report – Predominantly intracystic mucinous adenocarcinoma, with focal infiltrating adenocarcinoma, in a background of chronic pancreatitis. • Surgical margins were negative for carcinoma. • Ten out of ten resected lymph nodes were negative for carcinoma. Adrenal gland and spleen also negative for carcinoma.

18. Surgical Follow-up 5/25/04 • Dilemma – If there was no invasive cancer, her treatment would now be complete; the finding of invasive cancer, along with some previously elevated tumor makers and pulmonary nodules, are concerning. • Plan – redo all scans and serum markers, discuss at hepatobiliary conference, refer to medical oncologists.

19. Chronic Pancreatitis • Chronic pancreatitis is an inflammatory condition that results in permanent structural changes in the pancreas which lead to impairment of exocrine and endocrine function. • Can be asymptomatic over long periods of time, or can present as recurrent postprandial epigastric pain.

20. Clinical Features • The two primary clinical manifestations are abdominal pain and pancreatic insufficiency. • Pain is typically epigastric, often radiates to the back, often worse 15 to 30 minutes after eating, as the condition progresses, the pain tends to become more continuous. • Problems digesting food/absorption, fat malabsorption, glucose intolerance/diabetes.

21. Etiology 1 • Alcohol abuse (70-80% of cases; 5-10% of alcoholics develop CP) • Hereditary pancreatitis • Ductal obstruction (e.g., trauma, pseudocysts, stones, tumors, possibly pancreas divisum).

22. Etiology 2 • Tropical pancreatitis • Systemic disease (e.g., SLE, cystic fibrosis) • Autoimmune pancreatitis • Idiopathic pancreatitis • Mutations of the cystic fibrosis gene

23. Pathogenesis • Two consistent findings – • Hypersecretion of protein which is not compensated for by an increase in ductal bicarbonate secretion. This impairment is the basis for the secretin pancreatic function test used to diagnose CP. • The inflammatory histologic changes seen are patchy within the exocrine pancreas.

24. Diagnosis 1 • Labs and imaging procedures may be normal for several years. • Imaging options – plain films, CT, MRI,US, ERCP, EUS (endoscopic US). • Pancreatic function test: secretin stimulation test.

25. Diagnosis 2 • General rule - if labs normal, consider contrast abdominal CT; if normal, then ERCP or secretin testing. • Important to be secure in the diagnosis of CP in the setting of a significant change in the pain pattern, especially in the first 2 to 3 years when most diagnostic studies can be normal.

26. Complications • Pseudocysts (10% of patients) • Mechanical obstruction of the duodenum and common bile duct • Pancreatic ascites • Pleural effusion • Splenic vein thrombosis with portal hypertension • Pseudoaneurysm formation (e.g., splenic artery)

27. Cystic Lesions of the Pancreas • Retention cysts • Pseudocysts • Cystic neoplasms.

28. Pseudocysts • Result of pancreatic inflammation and necrosis. • Single or multiple, small or large, located either in or outside of the pancreas. • Most communicate with pancreatic ductal system, high concentrations of enzymes. • Walls formed by adjacent structures; fibrous lining; lack an epithelial lining seen in true cystic lesions.

29. Cystic Neoplasms • Mucinous cystadenoma/cystadenocarcinoma • Mucinous duct ectasia (intraductal papillary mucinous neopplasm) • Serous cystadenoma • Papillary cystic neoplasm

30. Mucinous cystadenoma • Most common cystic neoplasm. • Typically in middle-aged women. • Usually a mass lesion composed of one or more macrocystic spaces lined by mucous-secreting cells. • Most are malignant at time of diagnosis. High potential for malignant change.

31. Management • Resection is recommended given the high potential for malignant change. Distal pancreatectomy for lesions in the body or tail of the pancreas, and pancreaticoduodenectomy for pancreatic head lesions.

32. Uncertain Etiology • 1999 study involving 73 institutions/372 patients in France (Le Borne,J et al), showed an accurate preoperative diagnosis of tumor type of 20, 30, and 29% in patients confirmed to have serous cystadenomas, mucinous cystadenomas, and mucinous cystadenocarcinomas, respectively. • Most common recommendation is surgical resection of even moderately suspicious lesions in the body and tail of the pancreas.

33. References 1 • Le Borgne, J, de Calan, L, Partensky, D. Cystadenomas and cystadenocarcinomas of the pancreas – A multiinstitutional retrospective study of 398 cases. Ann Surg 1999; 230:152. • Malka, D, Hammel, P, Sauvanet, A, et al. Risk factors for diabetes mellitus in chronic pancreatitis. Gastroenterology 2000; 119:1324. • Steer, ML, Waxman, I, Freedman, S. Chronic pancreatitis. N Engl J Med 1995; 332:1482.

34. References 2 • UpToDate articles – Etiology and pathogenesis of chronic pancreatitis, Clinical manifestations and diagnosis of chronic pancreatitis, Treatment of chronic pancreatitis, Complications of chronic pancreatitis, Cystic lesions of the pancreas, Diagnosis and management of pseudocysts of the pancreas, Endoscopic ultrasound-guided fine-needle aspiration biopsy.