Gastrointestinal - Clinical Management Conditions Associated with Increased Gastrin and Secretin secretion

Gastrin Peptide hormone normally produced in antral portion of stomach in response to peptide fragments& amino acids (esp. tryptophan, phenylalanine) released from ingested foods. Physiologic gastrin production is also stimulated by gastric distention via acetylcholine. Gastrin release is inhibited when intragastric pH falls below 3.0. Gastrin stimulates acid production by oxyntic cells and growth of gastric mucosa. Supraphysiologic gastrin production as result of gastrinoma is called Zollinger-Ellison Syndrome (incidence 0.1 to 1 per million). ZE syndrome is often manifested by abdominal pain, ulcers of stomach and duodenum (90%), diarrhea (50%), and esophagitis. 75% occur sporadically and 25% are associated with MEN I syndrome (hyperparathyroidism, Pituitary adenomas, & Pancreatic islet cell tumors). Gastrinoma should be suspected in the setting of: ulcers recurrent/unresponsive to medical therapy/recurrent after ulcer surgery; family hx MEN I. Diagnosis: fasting serum gastrin levels > 200 pg/ml (values > 1000 pg/ml pathognomnic) and Basal gastric acid output > 15mEq/hr. Secretin stimulation testadminister 2u/kg IV ?measure serum gastrin levels at 5min. intervals for 30 minutes. Increase of > 200pg/ml above baseline is diagnostic. Treatment: Proton pump inhibitor. Imaging studies to localize the tumor and r/o metastasesmost commonly to regional LN and liver, but also lung, bone, skin, spleen. Most gastrinomas are located in the gastrinoma triangle (described by Passaro, et.al.)the area encompassed by the junction of cystic and CBD superiorly, junction of 2 and 3 portions of the duodenum inferiorly, and junction of neck and body of the pancreas medially. Somatostatin Receptor Scintigraphy (SRS)most sensitive imaging modality but limited by tumor sizedetects 96% of tumors > 2cm, 64% of tumors 1.1 to 2 cm, 30% of tumors < 1.1cm. SRS has same sensitivity as UTZ, MRI, CT, and selective angiography combined. Can also detect carcinoids/neuroendocrine tumors and bone, lung, liver metastases. Endoscopic ultrasound + SRS can increase detection of duodenal wall gastrinomas. At operation, Intra-op UTZ, duodenectomy w/ bimanual palpation of duodenal wall, Kocher maneuver should be performed. Operative management: Duodenal tumors (71% 1 portion, 21% 2 portion)full-thickness excision w/ primary closure; Pancreatic Tumorenucleation of tumor (distal pancreatectomy/whipple only if necessary); Liver metastasesshould be resected if limited and can be done safely. Prognosis: 49% pts w/ sporadic gastrinoma are disease free 5 yrs s/p surgery, 34% at 10 yrs vs. only 6% patients with gastrinoma assoc. w/ MEN I are disease free at 5 yrs, virtually none at 10 yrs . LN metastases has no impact on survival but liver metastases significantly decreases survival. Other conditions associated with increased gastrin: Atrophic gastrititis, pernicious anemia, vagotomy, renal failure, short gut syndrome, gastric outlet obstruction, retained excluded antrum, antral G cell hyperplasia.