1. ZOLLINGER ELLISON SYNDROME Uzor Chinelo 1492

2. Table of content.  Introduction  Epidemiology.  Pathogenesis.  Clinical presentation.  Examination and Tests.  Treatment.  Complication.  Prevention.  Prognosis.

3. Introduction  In 1955, Zollinger and Ellison first described the classic triad of fulminating peptic ulcer disease, gastric acid hypersecretion, and non-beta islet cell tumors.  Zollinger Ellison syndrome(ZE) is a condition that occurs with abnormal production of hormone gatsrin by a small tumour(gastrinoma), leading to damage to the gastric mucosa and increase gastrin in the blood.  The primary tumor is usually located in the duodenum, the pancreas, and abdominal lymph nodes, but ectopic locations have also been described (eg, heart, ovary, gall bladder, liver, kidney).

4. Epidemiology.  United States  ZES occurs in approximately 0.1-1% of all patients with duodenal ulcers. Its frequency of occurrence is reported to be approximately the same as insulinoma, the most common functioning pancreatic endocrine tumor.  Mortality/Morbidity  Currently, the morbidity and mortality of ZES is low because of improved medical and surgical management of the disease. Fewer than 5% of patients develop a complication, such as abdominal perforation, gastric outlet obstruction, or esophageal stricture.  Race  All races can be affected.  Sex  A slight male predominance exists, with a male-to-female ratio of 3:1.  Age  The mean age of onset of ZES is 43 years, with the patients with MEN 1/ZES presenting a decade earlier. Generally, a 5- to 7-year delay in diagnosis occurs. In a recent prospective study, fewer than 3% of patients were younger than 20 years, while 7% were older than 60 years at the time of disease onset.

5. Causes ZES is caused by a non–beta islet cell, gastrin- secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration. ZES may occur sporadically or as part of MEN 1(Multiple endocrine neoplasia type 1).

6. Pathogenesis  The symptoms of ZES are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa, leading to increased numbers of parietal cells and increased maximal acid output.  Gastrin by itself also stimulates acid secretion, resulting in increased basal acid secretion.  The large quantity of acid produced leads to gastrointestinal mucosal ulceration.  It also leads to diarrhea and malabsorption.  Malabsorption in ZES usually is multifactorial, being caused by direct mucosal damage by acid, inactivation of pancreatic enzymes, and precipitation of bile salts.

7. Clinical presentation. Abdominal pain is the most common symptom, present in 75% of patients. Typically, it is located in the upper abdomen and mimics that of peptic ulcer disease. This symptom is reported more frequently by men and patients with the sporadic form of ZES. Of patients with ZES, 73% have diarrhea, and this is the most common symptom in patients who have MEN 1/ZES and in female patients. The combination of diarrhea and abdominal pain is present in more than half the patients. Heartburn is the third most common symptom, and this symptom mimics gastroesophageal reflux disease (GERD). Other symptoms include nausea, vomiting, gastrointestinal bleeding, and weight loss. Gastrointestinal bleeding frequently is due to ulceration in the duodenum and is the presenting symptom in 25% of patients. In patients in whom MEN 1/ZES is suspected, a history indicative of nephrolithiasis, hypercalcemia, and pituitary disorders should be sought. A family history of nephrolithiasis, hyperparathyroidism, and gastrinoma also may be present.

8. Examination and tests  Abdominal CT scan.  Calcium infusion test.  Endoscopic ultrasound.  Exploratory surgery,  Gastric blood level.  Octreotide scan.

9. CT Scan of Tumour on ZE

10. Image showing the tumour on ZE

11. Treatment  Drugs called proton pump inhibitors (omeprazole, lansoprazole, and others) are now the first choice for treating this condition. These drugs reduce acid production by the stomach, and help the ulcers in the stomach and small intestine heal. They also relieve abdominal pain and diarrhea.  Surgery to remove a single gastrinoma may be done if the tumors have not spread to other organs.  Surgery on the stomach (gastrectomy) to control acid production is rarely needed(only about 30%-40% patients who have surgeries are cured).  For malignant tumors, radiation and chemotherapy may be offered.

12. Complication o Complications of ulceration include gastrointestinal bleeding and perforation. o Acid reflux can cause oesophagitis and oesophageal stricture. o The very high acid levels can inactivate pancreatic enzymes and precipitate bile salts so that malabsorption occurs. o Control of acid secretion limits complications. o Metastases: approximately 30-40% of gastrinomas are associated with liver metastases. At diagnosis, 5-10% of duodenal gastrinomas and 20-25% of pancreatic gastrinomas are associated with liver metastases. [3] 3 o It has been argued that the widespread use of PPIs may delay the diagnosis of ZES so that presentation is later and more advanced. o Failure to locate the tumour during surgery.

13. Prevention  If MEN1 is diagnosed, genetic counselling and genetic testing of family members is recommended.genetic counselling

14. Prognosis  Advanced tumour, node and metastasis (TNM) classification status; liver metastases, lymph node metastases, bone metastases.  Inadequate control of gastric acid hypersecretion.  Female gender.  Absence of MEN1.  Short disease history from onset to diagnosis.  Markedly increased fasting gastrin levels.  Presence of a large primary tumour; pancreatic primary gastrinoma.  Development of ectopic Cushing’s syndrome.  Ectopic Cushing’s syndrome develops in 5-15% of patients with advanced metastatic disease and has a very poor prognosis.  Most patients with ZES have lifelong hypergastrinaemia and require continuous PPI treatment.

15. 1. Mortellaro VE, Hochwald SN, McGuigan JE, et al. Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1. Am Surg. Aug 2009;75(8):730-3.[Medline].[Medline] 2. Alexakis N, Neoptolemos JP. Pancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2008;22(1):183- 205. [Medline].[Medline] 3. Anderson MA, Carpenter S, Thompson NW. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol. Sep 2000;95(9):2271-7. [Medline].[Medline] 4. Azimuddin K, Chamberlain RS. The surgical management of pancreatic neuroendocrine tumors. Surg Clin North Am. Jun 2001;81(3):511-25. [Medline].[Medline] 5. Baffy G, Boyle JM. Association of Zollinger-Ellison syndrome with pancreatitis: report of five cases. Dig Dis Sci. Aug 2000;45(8):1531-4. [Medline].[Medline] 6. Berger AC, Gibril F, Venzon DJ. Prognostic value of initial fasting serum gastrin levels in patients with Zollinger-Ellison syndrome. J Clin Oncol. Jun 15 2001;19(12):3051-7. [Medline].[Medline] 7. Bloomfeld R, Bornstein J, Jowell P. A report of a gastrinoma localized preoperatively by endoscopic ultrasound only and a review of the approach to imaging in Zollinger- Ellison syndrome. Dig Dis. 1999;17(5-6):316-8. [Medline].[Medline] 8. Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. Jun 2001;81(3):527-42. [Medline].[Medline] 9. Cadiot G, Jais P, Mignon M. Diagnosis of Zollinger-Ellison syndrome. From symptoms to biological evidence. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S147-52. [Medline].[Medline] 10. Campana D, Piscitelli L, Mazzotta E. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. Jun 2005;96(3):187-206. [Medl.

16. THANK YOU ALL