eMedicine Specialties > Gastroenterology > Stomach
Gastrinoma: Treatment & Medication
Updated: Aug 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Individualize the selection of treatment. Base treatment on factors related to ulcer disease, diarrhea, and malignant properties of the tumor. Antisecretory medications are helpful for controlling the manifestations of peptic acid disease and secretory diarrhea (secondary to hyperacidity).
- Proton pump inhibitors (eg, omeprazole, lansoprazole)
- These are highly effective drugs and are the drugs of choice for suppressing acid secretion. Long duration of action, fewer adverse effects, and high potency make them superior to H2 blockers.
- In 60% of patients, ulcer healing occurs within 2 weeks. In 90-100% of patients, healing occurs within 4 weeks.
- The recommended initial dose of omeprazole is 60 mg/d. Divided, twice-a-day dosing is suggested for doses greater than 80 mg/d. Once an effective maintenance dose is achieved, tapering of the medication, while monitoring symptoms and acid output, is suggested.
- H2-receptor antagonists
- The dose usually is 4-8 times higher than the dose administered to patients with peptic ulcer disease.
- Although a good success rate exists, this treatment has been reported to fail in 50% of patients.
- Chemotherapy
- This is indicated in patients with metastatic disease and in patients who are not candidates for surgery; however, it is not indicated for metastatic disease confined to the lymph nodes.
- Chemotherapy reduces tumor size and improves the symptoms secondary to metastatic effects of the tumor.
- A combination of streptozocin, 5-fluorouracil, and doxorubicin has been used, with the response rate reported to be as high as 65%.
- Granberg et al described a patient with almost complete response on treatment with Sandostatin LAR, a long-acting somatostatin analog.3
- Interferon or targeted radiotherapy may also be considered in patients who are not candidates for chemotherapy.
Surgical Care
- Surgical care is indicated for localized disease. Surgical resection of localized disease leads to a complete cure without any recurrence in 20-25% of patients with gastrinomas.
- Patients who have an isolated lesion or patients in whom the preoperative workup fails to localize the tumor should undergo laparotomy (by an experienced surgeon) with the intent to resect.
- It has been reported that Whipple pancreaticoduodenectomy affords the greatest probability for cure, particularly for MEN I associated gastrinomas, though also for sporadic tumors, since it results in removal of the entire gastrinoma triangle. However, the excellent long-term survival in patients with less complicated surgeries and the increased morbidity and mortality associated with the Whipple procedure make its general utility still unclear and recommended primarily for large, advanced tumors.
Consultations
- Gastroenterologist
- Endocrinologist
- Oncologist
- Surgeon
Medication
Immediate and sustained control of gastric acid hypersecretion is the most important aspect of disease management in patients with ZES because acid hypersecretion is the cause of essentially all symptoms and early morbidity and mortality.
Once ZES is considered and while appropriate diagnostic tests are conducted, acute acid secretion usually is best controlled with oral administration of a proton pump inhibitor (eg, omeprazole, lansoprazole, rabeprazole, esomeprazole). However, continuous infusion of an H2 antagonist (eg, ranitidine, cimetidine, famotidine), often at high doses, may be necessary for a small proportion of patients requiring rapid control of acid secretion who are unable to take oral medication.
Long-term management of acid secretion with a high dose of a proton pump inhibitor (or H2 blocker) is safe and effective.
Proton pump inhibitors
These agents bind to the proton pump of the parietal cell, inhibiting secretion of hydrogen ions into the gastric lumen. These agents are more effective than H2 blockers in relieving pain and healing ulcers. They are the drugs of choice in ZES. Although the drugs in this class are equally effective, omeprazole is used most commonly. Efficacy and tolerability of parenterally administered proton pump inhibitors in the acute treatment of patients with suspected ZES have not been established.
Omeprazole (Prilosec)
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump.
Titrate dose to achieve a BAO of 10 mEq/h. Gastric acid hypersecretion usually is controlled with doses <80 mg/d, but doses up to and even >200 mg/d have been used in some patients.
Adult
40-120 mg/d PO
Pediatric
Not established
May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Bioavailability may increase in elderly persons
Lansoprazole (Prevacid)
Inhibits gastric acid secretion. Titrate dose to achieve a BAO of 10 mEq/h. Efficacy and tolerability of IV administration in acute treatment of patients with suspected ZES have not been established.
Adult
30 mg PO qd
Pediatric
Not established
May decrease effects of ketoconazole and itraconazole; may increase theophylline clearance
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Consider adjusting dose in patients with liver impairment
Rabeprazole (Aciphex)
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump. Titrate dose to achieve a BAO of 10 mEq/h.
Adult
20-mg tab PO qd for 4-8 wk
Pediatric
Not established
May decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy
Esomeprazole magnesium (Nexium)
S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ -ATP pump at secretory surface of gastric parietal cells. Titrate dose to achieve a BAO of 10 mEq/h.
Adult
20 mg PO qd for 4 wk
Pediatric
Not established
Amoxicillin or clarithromycin may increase plasma levels when used concurrently; may reduce absorption of dapsone; may increase levels of diazepam and GI absorption of digoxin; may decrease absorption of iron, ketoconazole, and itraconazole
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Symptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy
H2-receptor antagonists
Inhibit the action of histamine on the parietal cell, which inhibits acid secretion. All agents in this class are equally effective. Intravenous administration may be helpful in patients who are unable to take oral medication.
Ranitidine (Zantac)
Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve BAO <10 mEq/h.
Adult
150 mg PO bid; not to exceed 600 mg/d
Alternatively, 50 mg/dose IV/IM q6-8h
Pediatric
<12 years: Not established
>12 years: 1.25-2.5 mg/kg/dose PO q12h; not to exceed 300 mg/d; alternatively, 0.75-1.5 mg/kg/dose IV/IM q6-8h; not to exceed 400 mg/d
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Cimetidine (Tagamet)
Inhibits histamine at H2 receptors of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve BAO <10 mEq/h.
Adult
150 mg PO qid; not to exceed 600 mg/d; 50 mg/dose IV/IM q6-8h; not to exceed 400 mg/d
Pediatric
Not established
Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Elderly persons may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur
Famotidine (Pepcid)
Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations. Titrate dose to achieve a BAO of 10 mEq/h.
Adult
40 mg PO bid
Pediatric
Not established
May decrease the effects of ketoconazole and itraconazole
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Chemotherapeutic agents
Indicated in metastatic disease and in patients who are not candidates for surgery. Reduce tumor size and improve symptoms secondary to metastatic effects of the tumor. A combination of streptozocin, 5-fluorouracil, and doxorubicin has been used, with a response rate of as high as 65%.
Streptozocin (Zanosar)
Inhibits DNA synthesis without significantly affecting bacterial or mammalian RNA or protein synthesis.
Adult
Administer under direction of oncologist experienced in both use of medication and treatment of this disease
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor closely for evidence of renal, hepatic, or hematopoietic toxicity; perform CBC count and LFTs weekly
5-Fluorouracil (Adrucil)
Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid, inhibiting thymidylate synthetase, and, subsequently, inhibiting cell proliferation.
Adult
Administer under direction of oncologist experienced in both use of medication and treatment of this disease
Pediatric
Not established
Leucovorin may enhance toxicity
Documented hypersensitivity; poor nutritional status; depressed bone marrow function; potentially serious infections
Pregnancy
D - Unsafe in pregnancy
Precautions
Discontinue use if stomatitis or esophagopharyngitis, rapidly falling WBC count, leukopenia (WBC <3500/mm3), intractable vomiting, diarrhea, GI ulceration and bleeding, thrombocytopenia (platelets <100,000/mm3), or hemorrhage occurs
Doxorubicin (Adriamycin, Rubex)
Inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.
Adult
Administer under direction of oncologist experienced in both use of medication and treatment of this disease
Pediatric
Not established
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity
Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression
Pregnancy
D - Unsafe in pregnancy
Precautions
Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function
More on Gastrinoma |
| Overview: Gastrinoma |
| Differential Diagnoses & Workup: Gastrinoma |
 Treatment & Medication: Gastrinoma |
| Follow-up: Gastrinoma |
| References |
| Further Reading |
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References
Ruiz-Tovar J, Priego P, Martinez-Molina E, et al. Pancreatic neuroendocrine tumours. Clin Transl Oncol. Aug 2008;10(8):493-7. [Medline].
Kohan E, Oh D, Wang H, et al. Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with Zollinger Ellison syndrome. Diagn Ther Endosc. 2009;2009:298381. [Medline]. [Full Text].
Granberg D, Jacobsson H, Oberg K, Gustavsson J, Lehtihet M. Regression of a large malignant gastrinoma on treatment with Sandostatin LAR: a case report. Digestion. 2008;77(2):92-5. [Medline].
Campana D, Piscitelli L, Mazzotta E. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. Jun 2005;96(3):187-206. [Medline].
Del Valle J, Scheiman J. Zollinger-Ellison Syndrome. Textbook of Gastroenterology, 4th Edition. 2003;1377-1388.
Delvalle J, Yamada T. Zollinger-Ellison Syndrome. Textbook of Gastroenterology. 1995;1430.
Feldman M, Sleisenger MW, McGuigan JE. Zollinger-Ellison syndrome and other hypersecretory states. In: Feldman M, Scharschmidt BF, Sleisenger M, Zorab R, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 6th ed. Philadelphia, Pa: WB Saunders; 1998:. 679-90.
Hirschowitz BI. Zollinger-Ellison syndrome: pathogenesis, diagnosis, and management. Am J Gastroenterol. Apr 1997;92(4 Suppl):44S-48S; discussion 49S-50S. [Medline].
Jensen RT, Gibril F. Somatostatin receptor scintigraphy in gastrinomas. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S179-85. [Medline].
Mignon M, Cadiot G. Natural history of gastrinoma: lessons from the past. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S98-103. [Medline].
Nobels FR, Kwekkeboom DJ, Coopmans W. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. Aug 1997;82(8):2622-8. [Medline].
Norton JA. Gastrinoma: advances in localization and treatment. Surg Oncol Clin N Am. Oct 1998;7(4):845-61. [Medline].
Norton JA. Surgical treatment and prognosis of gastrinoma. Best Pract Res Clin Gastroenterol. Oct 2005;19(5):799-805. [Medline].
Norton JA, Fang TD, Jensen RT. Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J Natl Compr Canc Netw. Feb 2006;4(2):148-53.
Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. Oct 2005;19(5):753-81.
Passaro E, Howard TJ, Sawicki MP. The origin of sporadic gastrinomas within the gastrinoma triangle: a theory. Arch Surg. Jan 1998;133(1):13-6; discussion 17. [Medline].
Pellicano R, De Angelis C, Resegotti A. Zollinger-Ellison syndrome in 2006: concepts from a clinical point of view. Panminerva Med. Mar 2006;48(1):33-40.
Price TN, Thompson GB, Lewis JT, Lloyd RV, Young WF. Zollinger-Ellison syndrome due to primary gastrinoma of the extrahepatic biliary tree: three case reports and review of the literature. Endocr Pract. Jun 2 2009;1-38. [Medline].
Sugg SL, Norton JA, Fraker DL. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann Surg. Aug 1993;218(2):138-44. [Medline].
Wong H, Yau T, Chan P, et al. PPI-delayed diagnosis of gastrinoma: oncologic victim of pharmacologic success. Pathol Oncol Res. Aug 20 2009;[Medline].
Further Reading
- Gastric Ulcers
- Multiple Endocrine Neoplasia [in the Pediatrics: General Medicine section]
- Neoplasms of the Endocrine Pancreas [in the Oncology section]
- Pancreas, Islet Cell Tumors [in the Radiology section]
- Zollinger-Ellison Syndrome [in the Gastroenterology section]
- Zollinger-Ellison Syndrome [in the Pediatrics: General Medicine section]
Clinical Trials
- Combination Chemotherapy and Bevacizumab in Treating Patients With Advanced Neuroendocrine Tumors
- Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors
- Treatment of Zollinger-Ellison Syndrome With Prevacid
- ACR Appropriateness Criteria® acute abdominal pain and fever or suspected abdominal abscess. American College of Radiology - Medical Specialty Society. 1996 (revised 2006). 7 pages. NGC:005138
- ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. American Society of Clinical Oncology - Medical Specialty Society. 996 (revised 2006 Nov 20). 15 pages. NGC:005328
- ASGE guideline: the role of endoscopy in the diagnosis and the management of cystic lesions and inflammatory fluid collections of the pancreas. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2005 Mar. 8 pages. NGC:004190
- ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2005 Jul. 8 pages. NGC:004486
- Quality indicators for endoscopic retrograde cholangiopancreatography. American College of Gastroenterology - Medical Specialty Society; American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 6 pages. NGC:004967
Keywords
gastrinoma, Zollinger-Ellison syndrome, ZES, ZE syndrome, pancreatic tumor, pancreas tumor, duodenal tumor, duodenal wall tumor, lymph node tumor, gastrin-secreting tumor, tumor, pancreatic islet cell tumors, malignancy, malignant tumor, basal acid output, BAO, ulcer, severe ulcer disease, multiple endocrine neoplasia type I, MEN type I, ulcerogenic islet cell tumor
