ZES

Zollinger Ellison syndrome

1. Seminar on Zollinger Ellison Syndrome Presenter : Dr Biswajit Deka

2. History Almost 63 years ago, in 1955, Zollinger and Ellison reported the clinical course of two women with severe ulcer diatheses who presented with perforated jejunal ulcers. Both had massive gastric acid hyper secretion and each was ultimately found to have a non‐insulin secreting islet cell tumour. The investigators postulated that an unknown hormone secreted from these islet cell tumours was the cause of the massive gastric acid output that resulted in these intractable peptic ulcer syndromes

3. Robert M. Zollinger and Edward H. Ellison

4. ZES ZES is caused by the uncontrolled secretion of abnormal amounts of gastrin by a duodenal or pancreatic neuroendocrine tumour(i.e gastrinoma) 80% sporadic 20% inherited

5. Inherited / familial form- a/w: MEN-1(parathyroid, pituitary, pancreatic or duodenal tumours) Gastrinoma is the MC pancreatic tumour in MEN1 MEN1: multiple gastrinoma tumour ; surgical cure less common. Sporadic gastrinoma : often solitary ; more often amenable to surgical cure

6. Gartrinoma Gastrin secreting PNET >60% are malignant MC pancreatic tumour in MEN1 2nd MC functional pancreatic endocrine tumour Incidence : 1 per 2.5 million 1st described in 1955 by Zollinger and Ellison

7. Gastrin produced by islet cell tumours is not subjected to the normal stimulation by amino acids & peptides in the stomach or by gastric distension. Not suppressed by high luminal pH & can be stimulated (instead of inhibited) by secretin . Mean age at diagnosis : 50 yrs Male > female (60:40)

8. Tumour distribution Majority of gastrinomas occur within pancreas ; a significant no is extra pancreatic Over 90% : within gastrinoma triangle Duodenal tumour: MC non pancreatic lesions , >60% of the gastrinomas Duodenal tumours are smaller, slow growing & less likely to metastasize than pancreatic lesions

9. Less common extra pancreatic sites : stomach bones ovaries heart liver lymph nodes gastrinomas are occasionally localised to LN in this region and it is unclear whether lymph nodes can be a true primary site or whether they represent metastases from occult primary tumours in pancreas or duodenum

10. Clinical presentation Pts with ZES fulminant peptic ulcer diathesis, acid hyper secretion non beta islet cell tumour of pancreas Hypergastrinemia - peptic acid hyper secretion and refractory peptic ulcer disease Duodenal ulcers are MC , but jejunal ulceration may also occur Jejunal ulcer : should raise suspicion of gastrin secreting PNET

11. 75% - abdominal pain ; 2/3rd have diarrhoea In 10-20% diarrhoea - only symptom This acid induced diarrhoea is stopped by nasogastric aspiration of gastric secretions, differentiating it from other secretory diarrhoeas. High acid production can lower the normal pH of duodenum and inactivate pancreatic enzymes, leading to diarrhoea .

12. >1/3rd of the patients have sign & symptoms of GERD and this no appears to be increasing . GI bleeding (melena / hematochezia ) Weight loss, nausea , vomiting Jejunal ulcer perforation : 7%

13. Diagnosis ZES considered in all patients with 1. intractable peptic ulcers (jejunal ulcers) 2. severe esophagitis 3. persistent secretory diarrhoea . The diagnosis depends on the presence of hypergartrinemia & increase secretion of gastric acid.

14. Gastrin : normal upto 100 pg/ml >1000pg/ml : gastrinoma (provided that pt demonstrated increased gastric acid secretion) In the workup of ZES, all PPI must be stopped 2 weeks before testing gastrin level An elevated s/gastrin level coupled with a pH <2 in gastric aspirate is diagnostic of ZES

15. Doubtful cases : ZES confirmed by Secretin stimulation test. In this test fasting gastrin level is measured before secretin ( 2 IU/kg ) is administered iv , and subsequent samples are obtained 2,5,10 & 20 minutes. Gastrin level > 200 pg/ml after administration of secretin are noted in 87% of patients, with no false positive results

16. Patients with gastrinoma usually have a BAO> 15 mEq/hr or > 5 mEq/hr with previous procedure for peptic ulcer Patients with gastrinoma should have serum calcium & parathyroid hormone level determined to rule out MEN1 and, if present, parathyroidectomy should be considered before resection of gastrinoma Transabdominal USG : specific ; not sensitive CT detect : > 2cm in size EUS : more sensitive

17. Transabdominal USG : specific not sensitive. CT detect : > 2cm in size EUS : more sensitive

18. Currently pre-op IOC : somatostatin receptor scintigraphy (the octretide scan ) Gastrinoma cells contain type 2 somatostatin receptors that bind the indium labeled somatostatin analogue (octreotide). Most imp procedure: locating gastrinoma in intraoperative exploration

19. Management The Mx of gastrinoma in MEN1 is controversial because the pts are often not cured by operation and tumours tend to be small and multiple. High dose PPI Highly selective vagotomy Gastrectomy for ZES : no longer indicated.

20. The presence or absence of malignant disease is the most imp prognostic factor . In 5-8% cases the surgeon is unable to localise the tumour intra operatively Exploration include entire abdomen ,from undersurface of liver to pelvic floor Intra operative USG should routinely be performed to identify the small lesions or liver metastasis Transillumination of duodenum with intra operative endoscopy may help identify small submucosal lesions

21. A 3cm duodenotomy on antero-lateral portion of 2nd part of duodenum is made which allows detection of lesions < 1cm Duodenotomy detects 25-30% of tumour not seen on preoperative imaging Small encapsulated tumour : enucleation