Stomach_ZES Flashcards
Where is gastrin synthesized?
G cells, open-ended endocrine cells found predominantly in the gastric antrum
In general gastrin release is stimulated by:
Digestive proteins (e.g. phenylalanine and tryptophan), calcium, epinephrine, achlorhydria and gastric distension
Vagal parasympathetic control of gastrin physiology is stimulatory or inhibitory?
Both
T/F: atropine blocks gastrin stimulation?
TRUE
Gastrin release is stimulated by what specific proteins?
bobesin or gastrin releasing peptide (GRP
Gastrin is inhibited by what specific hormones?
Somatostatin, secretin, glucagon, gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP)
What oncogenes are implicated for in gastrinomas pathogenesis?
c-myc and Her-2/neu
What tumor-supressor genes are implicated in gastrinoma pathogenesis?
MEN-1, DPC4/Smad and p16INK4a
What are the markers for aggressive biologic behavior of neuroendocrine tumors (e.g. gastrinomas)?
Oncogenes, RET-protooncogenes being present. Over expression of EGF-R, IGFlr, chromosomal abnl, chromosome 1q, chromosome 22q and X chromosome.
MEN-1 tumor-suppressor gene is on what chromosome?
11q13
MEN-1 encodes what protein?
menin
What does menin do?
It is a nuclear protein that alters tumor growth factor beta signanling, regulates NFKB transcription and man fxn in DNA repair and synthesis.
When is Zollinger-Ellison diagnosed
Usually in the 5th decade of life
Patients with MEN-1 have onset of ZES at what age
33 years versus 44 years in sporadic cases
What should prompt a physician to test for ZES?
- Combination of abdominal pain, diarrhea, wt loss. 2. Recurrent or refractory ulcers. 3. Prominent gastric rugal folds. 4. GI symptoms w/ or w/o ulcers occuring in an MEN-1 pt.
What is the initial diagnostic test for a patient suspected of having ZES?
Fasting serum gastrin when patient has been off PPIs for 72 hours.
Is fasting hypergastrinemia along enough to establish the dx of ZES?
No
Give the differential for hypergastrinemia
Pernicious anemia, atrophic gastritis, pharmacologic suppression, H. pylori infection, GOO, antral G-cell hyperplasia, reatined antrum, short bowel syndrome, renal failure.
After a fasting serum gastrin, what is the next test in the work-up for ZES?
Gastrin-stimulation test
Is it necessary to discontinue PPIs for the secretin stim test for ZES?
No
How is a secretin stimulation test for ZES done?
Give 0.4 mg/kg of secretin by IV push, then measure gastrin at 0, 2, 5, 10, 15 and 30 minutes
What is a positive secretin stimulation test for ZES?
An increase in postsecretin gastrin of 200 pg/mL. However, most authorities use an increment of 110 pg/mL
What % of patients with a gastrinoma have MEN-1?
25%
All patients with a gastrinoma should be screened for?
MEN-1 with a serum measurement of calcium, phosphorus, parathyroid hormone and prolactin at presentation and periodically during follow-up.
What imaging tests are used to localize a gastrinoma?
US, CT, MRI, angiography, somatostain scintigraphy with octreotide, EUS or selective arterial secretin or calcium stimulation with sampling from the hepatic veins.
What is the difference in sensitivity of EUS in detecting gastrinomas in the duodenum vs the pancreas?
Pancreas: 75-100%. Duodenum: 25-63%.
What is the medical treatment of gastric acid hypersecretion for ZES patients?
PPIs, often at doses greater than commonly recommended for typical ucler disease.
If the primary gastrinoma is not found on imaging, what is indicated?
Surgical exploration.
What % of patients with negative imaging will NOT have their primary gastrinoma found on ex lap?
15%.
Give the borders of the gastrinoma triangle
Confluence of cystic and CBD superiorly, 2nd and 3rd portions of the duodenum inferiorly, and neck/body of the pancreas medially
Principles of surgical exploration for finding the gastrinoma
Wide Kocher maneuver, mobilization of body and tail for bimanual palpation, intraoperative US, duodenotomy to explore the duodenal mucosa and sampling of lymph nodes in the gastrinoma triangle.
In the duodenum, where are most gastrinoma primaries located?
In the 1st and 2nd portion
How large are most gastrinoma primaries in the duodenum?
Often < 2mm, most are <1 cm
When a nodule suspected to be a gastrinoma is found on exploration of the duodenum, what is the next step?
Send it for frozen section - can be brunner’s gland hyperplasia
Can lymph nodes be a primary source of gastrinomas?
Yes - literature suggests 10% of sporadic cases
When can one be diagnosed with a lymph node primary gastrinoma?
The patient cannot have MEN-1 and only after 10 years after suspected diagnosis as the primary can be found on another exploration
What is required of pts diagnosed with lymph node primary gastrinoma?
Yearly fasting and secretin-stimulated serum gastrin levels
When can pancreatic gastrinomas be enucleated?
If they are < 2cm and do not involve the duct
If a gastrinoma either involves the pancreatic duct or is >2 cm what surgery is indicated?
Pancreaticoduodenectomy. Lesions in the body and tail - a distal pancreatectomy and splenectomy is required
What is the definition of biochemical cure following surgery for sporadic ZES?
Normal fasting and secretin-stimulation gastrin level
What is the initial cure rate for sporadic ZES?
35-60%
With long-term follow-up, recurrent hypergastrinema may occur in what % of patients?
40%
Surgical resection increases disease-specific survival for sporadic ZES by what % at 15 and 20 years?
15 years: 98% for pts who underwent an operation and 74% for non-op pts. 20 years: 60 (op) and 20% (non-op)
Why should an MEN-1 patient undergo parathyroid surgery (if indicated) before surgery for ZES?
Removing the constant stimulation for hypercalcemia (parathyroid) reduces the serum gastrin levels
What procedure is done for hyperparathyroidism in MEN-1 patients?
Either subtotal parathyroidectomy (3.5 glands) or total parathyroidectomy with autotransplantation
How does the surgical approach change for MEN-1 pts vs sporaic ZES pts?
MEN-1: image-negative pts should NOT undergo exploration (low cure rates). Non-stage IV Image-positive pts should undergo exploration. All sporadic non-Stage IV ZES should undergo exploration.
T/F: Biochemical cure in MEN-1 ZES patients rarely results in a biochemical cure.
T. Which is why if the pt has image-negative ZES they should not undergo an exploration
If an MEN-1 ZES patient has an image-positive nodule, why should they undergo resection?
Because it has been shown to improve survival independent of biochemical cure.
Why are data on liver debulking for gastrinomas difficult to make any conclusions regarding treatment?
Gastrinoma patients are usually lumped in with neuroendocrine and carcinoid patients.
With regards to survival, what is the general consensus for liver resection for metastatic neuroendocrine tumors?
5-year survival ranges from 70-100% with liver resection for metastatic neuroendocrine tumors (no % given for pts who did not undergo rsxn)
Is there evidence to support liver transplantation for metastatic neuroendocrine tumors?
Yes. Should be restricted to pts with primary tumor resected and unresponsive to treatments of metastatic disease (e.g. somatostatin therapy), younger than 50, low Ki67 staining and regular E-cadherin staining.
