0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Special Feature |

Image of the month—diagnosis FREE

[+] Author Affiliations

Section Editor: Grace S. Rozycki, MD

More Author Information
Arch Surg. 2003;138(8):914. doi:10.1001/archsurg.138.8.913.
Text Size: A A A
Published online

Figure 1. Hypertrophic folds within the body of the stomach, and a normal antrum.

Figure 2. Duodenum and proximal jejunum revealing multiple ulcers.

Gastrinomas are rare neuroendocrine tumors that secrete gastrin, producing severe peptic ulcer or even jejunal ulcer disease. zollinger and ellison1 were the first to attribute marked peptic ulcer disease in association with gastric acid hypersecretion and tumors of the pancreas. the discovery of gastrin in the 1960s helped further delineate the pathophysiology.2

Gastrinomas are the most common malignant pancreatic islet cell tumors. the incidence is rare, occurring in 0.1 to 3 million individuals per year.3 About 25% are associated with inherited familial disorders, such as multiple endocrine neoplasia type 1, and the remainder are sporadic. the incidence among patients with peptic ulcer disease is 0.1%; however, this approaches 1% in patients with recurrent disease.2 Sixty percent are malignant, of which 25% are especially virulent and grow rapidly.3,4 Ninety percent are located within the gastrinoma triangle, defined as the junction of the cystic duct and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially.2

Patients typically have symptoms of epigastric pain, heartburn, dysphagia, or diarrhea. the mean age at onset is 50 years (range, 7-90 years), with a male-female predominance of 2:1. ninety percent of patients have peptic ulceration, and 10% to 15% also have distal duodenal and jejunal ulcers.3 Hypertrophic gastric folds within the proximal stomach are caused by gastrin stimulation. forty percent of patients have secretory watery diarrhea associated with significant malnutrition and weight loss. about 20% of patients will have diarrhea as their sole complaint. ten percent will have evidence of severe reflux by endoscopy and can exhibit strictures of the esophagus.3

A fasting serum gastrin level is the initial screening test for gastrinoma. a level greater than 100 pg/ml (47.7 pmol/l) indicates hypergastrinemia, and a level greater than 1000 pg/ml (477 pmol/l) is pathognomonic. our patient's gastrin level was 1120 pg/ml (534.2 pmol/l). the secretin stimulation test can distinguish gastrinoma from other sources of hypergastrinemia.

Localization studies historically have been poor. ultrasound, computed tomography, and angiography have sensitivities of 21%, 59%, and 68%, respectively, and specificities of 92%, 95%, and 94%.2 To date, the most accurate test is somatostatin receptor scintigraphy (sensitivity, ˜90%; specificity, ˜100%),3,5 which localized the tumor to an isolated area at the descending duodenum and head of the pancreas.

Treatment of zollinger-ellison syndrome is controversial. historically, surgical cure rates for gastrinoma excision have been poor, with only a 5% success rate, and total gastrectomy has been the treatment of choice.2 The advent of powerful acid-suppressing medications has prompted some authors to recommend medical therapy alone.6 Mortality from complications of severe ulcer disease has dramatically dropped, owing to these medical regimens.7 However, tumor size and risk of rapid growth, with a 60% potential for malignancy, confer a much greater risk of mortality.3,4,7 Patients with sporadic gastrinomas without evidence of metastatic disease should be offered surgical exploration. although surgery is seldom curative for patients with zollinger-ellison syndrome and multiple endocrine neoplasia type 1, liver metastasis may be preventable and overall survival, prolonged.3

Surgical exploration involves full abdominal exploration, focusing in the gastrinoma triangle. intraoperative ultrasound, intraoperative endoscopic transillumination, and longitudinal duodenotomy can help identify small tumors.3,4 Most tumors can be enucleated but may require extensive resection if the tumor is larger than 2 cm. regional lymph nodes should also be removed for histologic evaluation. our patient had a 1 cm-gastrinoma resected from the wall of the second portion of the duodenum. an enlarged local node was negative for metastatic disease. immediate cure rates are 14% to 58%, and long-term cure rates are between 31% and 81%. the 5- and 10-year survival rates for resection of sporadic gastrinomas are 100% and 95%, respectively.3,4

Corresponding author and reprints: james c. hebert, md, university of vermont, fletcher house, 111 colchester ave, burlington, vt 05401 (e-mail: james.hebert@vtmednet.org).

Zollinger  RMEllison  EH Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann surg. 1955;142709- 728
Howard  TJPassaro  E Gastrinoma: new medical and surgical approaches. Surg clin north am. 1989;69667- 681
PubMed
Dolan,  JPNorton  JA Neuroendocrine tumors of the pancreas and gastrointestinal tract and carcinoid disease. Norton  JABollinger  RRChang  AE  et al. Surgery basic science and clinical evidence. New York, NY Springer2001;
Norton  JAFraker  DLAlexander  HR  et al.  Surgery to cure the zollinger-ellison syndrome. N engl j med. 1999;341635- 644
PubMed
Alexander  HRFraker  DLNorton  JA  et al.  Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with zollinger-ellison syndrome. Ann surg. 1998;228228- 238
PubMed
Hirschowitz  BI Clinical course ofnonsurgically treated zollinger-ellison syndrome. Front gastrointest res. 1995;23360- 371
Yu  FVenzon  DJSerrano  J  et al.  Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing zollinger-ellison syndrome. J clin oncol. 1999;17615- 630
PubMed

Tables

References

Zollinger  RMEllison  EH Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann surg. 1955;142709- 728
Howard  TJPassaro  E Gastrinoma: new medical and surgical approaches. Surg clin north am. 1989;69667- 681
PubMed
Dolan,  JPNorton  JA Neuroendocrine tumors of the pancreas and gastrointestinal tract and carcinoid disease. Norton  JABollinger  RRChang  AE  et al. Surgery basic science and clinical evidence. New York, NY Springer2001;
Norton  JAFraker  DLAlexander  HR  et al.  Surgery to cure the zollinger-ellison syndrome. N engl j med. 1999;341635- 644
PubMed
Alexander  HRFraker  DLNorton  JA  et al.  Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with zollinger-ellison syndrome. Ann surg. 1998;228228- 238
PubMed
Hirschowitz  BI Clinical course ofnonsurgically treated zollinger-ellison syndrome. Front gastrointest res. 1995;23360- 371
Yu  FVenzon  DJSerrano  J  et al.  Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing zollinger-ellison syndrome. J clin oncol. 1999;17615- 630
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles