1. Joint Hospital Surgical Grand Round 1/2010 Neuroendocrine Tumour of Pancreas Chan Hoi Yee Princess Margaret Hospital

2. Neuroendocrine Gastroenteropancreatic tumours  Heterogeneous group of tumours located in gastric mucosa, pancreas, small and large intestine  Rare  3-10 cases per million  Sporadic cases: 30-50 years old  MEN I: - 80 % of patients with MEN I syndrome have one or more pancreatic tumour - 80 % of patients with MEN I syndrome have one or more pancreatic tumour - 10-30 years old - 10-30 years old - gastrinoma and insulinoma most common - gastrinoma and insulinoma most common

3. Nonfunctional vs Functional

4. Neuroendocrine Tumour of Pancreas Ramage J et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours.Gut. 54 Supplement IV:iv1-iv16, June 2005.

5. Gastrinoma

6. Gastrinoma  0.4-5 per million of people per year  0.1 % DU have ZES  20% gastrinoma associated with MEN I  50-60% malignant at time of diagnosis

7. Symptoms V Fendrich et al. Management of sporadic and multiple endocrine neoplasm type I gastrinoma. British Journal of Surgery 2007;94:1331-1341

8. Investigations Fasting serum gastrin test:  Normal: 100pg/ml  Diagnostic: > 1000 pg/ml  Suggestive: > 200 pg/ml

9. Investigations Gastric acid analysis  pH < 2  Basal secretion rate - > 15 mEq/h (no previous gastric surgery) - > 15 mEq/h (no previous gastric surgery) - > 5 mEq/h (with previous gastric surgery) - > 5 mEq/h (with previous gastric surgery)  Basal-to- max acid output ratio > 0.6

10. Secretin Stimulation Test  Low pH  duodenal S cells secrete secretin  secrete bicarbonate rich pancreatic juice  Secretin receptor found on surface of neuroendocine cells  release of gastrin  Not stimulate normal G cells to secrete gastrin

11. Secretin Stimulation Test  2μg/kg secretin iv  Measure blood gastrin level at 0,2,5,10,15,20 mins  Positive if rise in blood gastrin level > 200pg/ml by 15 mins  Sensitivity: 94%  Specificity: 100%

12. Calcium Stimulation Test  Calcium stimulate the release of gastrin from gastrinoma cells  5 mg/kg 10% ca gluconate infused over 3 hrs  Measure blood gastrin level at 0, 30, 60, 90, 120, 150 and 180 mins  Positive test if increased > 395 pg/ml  Sensitivity: 62%  Specificity: 100 %

13. Investigations

14. Localization  80-90 % in gastrinoma triangle V Fendrich et al. Management of sporadic and multiple endocrine neoplasm type I gastrinoma. British Journal of Surgery 2007;94:1331- 1341

15. Localization for Sporadic Gastrinoma V Fendrich et al. Management of sporadic and multiple endocrine neoplasm type I gastrinoma. British Journal of Surgery 2007;94:1331-1341

16. Localization of Sporadic Gastrinoma  Surgical exploration and IOUS  Sensitivity 95%  intraoperative endoscopy and transillumination of duodenal wall  duodenotomy Sugg SI et al. A prospective study of intraoperative Sugg SI et al. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinoma. methods to diagnose and resect duodenal gastrinoma. Ann Surg. 1993, 218:138-144 Ann Surg. 1993, 218:138-144

17. Treatment for Gastrinoma Medical vs Operation????

18. Medical Treatment of Gastrinoma  Long term PPI  Highly effective tx - 60%: ulcer healed within 2 weeks - 60%: ulcer healed within 2 weeks - 90-100%: ulcer healed within 4 weeks - 90-100%: ulcer healed within 4 weeks  reduce acid output within 1 hr of receiving an initial iv 80mg pantoprazole Lew EA et al. Intravenous pantoprazole rapidly controls Lew EA et al. Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with ZES. gastric acid hypersecretion in patients with ZES. Gastroenterology 2000; 118:696-704 Gastroenterology 2000; 118:696-704

19. Medical Treatment of Gastrinonma  Most developed gastroesophageal reflux, diarrhea, dyspepsia or endoscopic evidence of reflux within 2 weeks after discontinuation of PPI Metz DC et al. Prospective study of the need for long term Metz DC et al. Prospective study of the need for long term antisecretory therapy in patients with ZES following successful antisecretory therapy in patients with ZES following successful curative gastrinoma resection. Aliment Pharmacol Ther 1993; curative gastrinoma resection. Aliment Pharmacol Ther 1993; 7:247-256 7:247-256  Increasing patient who died from malignant nature of gastrinoma

20. Operative Treatment of Gastrinoma  Aims: - relief of symptoms - relief of symptoms - decreased burden of tumour - decreased burden of tumour - decreased liver or distant metastasis - decreased liver or distant metastasis

21. Operative Treatment of Gastrinoma  A retrospective study demonstrated increased survival in patients received operation (Jeffrey et al. Surgery increases survival in patients with gastrinoma. Ann of surg 2006 243 (3); 410-419)  1980 – 2004  160 patients had operation  35 patients did not received operation - refused surgery - refused surgery - high risk for surgery - high risk for surgery - no lesions can be identified during pre-op imaging in patients with MEN I - no lesions can be identified during pre-op imaging in patients with MEN I  Types of operation: - enucleation - enucleation - duodenotomy - duodenotomy - pylorus preserving pancreaticoduodentectomy - pylorus preserving pancreaticoduodentectomy - peripancreatic LN dissection - peripancreatic LN dissection

22. Operative Treatment of Gastrinoma  Jeffrey et al. Surgery increases survival in patients with gastrinoma. Ann of surg 2006 243 (3); 410-419)

23. Operative Treatment of Gastrinoma Jeffrey et al. Surgery increases survival in patients with gastrinoma. Ann of surg 2006 243 (3); 410-419)

24. Operative Treatment of Gastrinoma V Fendrich et al. Management of sporadic and multiple endocrine neoplasm type I gastrinoma. British Journal of Surgery 2007;94:1331- 1341

25. Prognostic Factors  A retrospective analysis of 3851 patients which identify factors predicting survival after operation for PNETs Karl Y et al. Prognostic score predicting survival after Karl Y et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumours, analysis resection of pancreatic neuroendocrine tumours, analysis of 3851 patients. Ann of Surg 2008 (247); 490-500 of 3851 patients. Ann of Surg 2008 (247); 490-500  All underwent operation from 1985 -2004

26. Prognostic Factors Karl Y et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumours. Ann of Surg 2008; 247(3): 490-500

27. Prognostic Score Karl Y et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumours. Ann of Surg 2008; 247(3): 490-500

28. Prognostic Score Karl Y et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumours. Ann of Surg 2008; 247(3): 490-500

29. Conclusion  High suspicious  Lots controversies in management of gastrinoma  Surgery can provide cure and improved long term survival  Patients with advanced age, poor differentiated tumour and liver metastasis will have poor prognosis

30. Conclusion  Need more studies  Studies were difficult to perform - rare disease - rare disease - 20-25% patients have ZES with MEN I  likely recurrent and difficult to cure - 20-25% patients have ZES with MEN I  likely recurrent and difficult to cure - only 25% had aggressive course  need long term follow-up - only 25% had aggressive course  need long term follow-up

31. Thank You