Abstract
Since 1980, 73 patients with Zollinger-Ellison syndrome (ZES) without radiographic evidence of liver metastases were studied on a prospective protocol including medical management of gastric acid hypersecretion, extensive radiographic tumor localization, and exploratory surgery to find and resect gastrinoma for potential cure. Each patient had gastric acid hypersecretion effectively controlled with either H2-blockers or omeprazole. Patients were divided prospectively into two groups, with all patients undergoing the same preoperative localization studies and extensive laparotomy. In contrast to group 1 (1980-1986) (36 patients), group 2 (1987-Oct. 1990) (37 patients) also underwent additional procedures (transillumination and duodenotomy) at surgery to find duodenal gastrinomas. Preoperative imaging studies localized tumor in 38 (52%) patients, and portal venous sampling for gastrin determinations was positive in 49 (67%) patients. Gastrinomas were found and resected in 57 (78%) patients. Significantly more gastrinomas (92% of patients) were found in group 2 than in group 1 patients (64%) (p less than 0.01). This increase was due to increased numbers of duodenal gastrinomas in group 2 than in group 1 patients (43% versus 11%; p less than 0.01). The increased ability to find duodenal gastrinomas did not significantly improve the immediate disease-free rate, which was 58% for all patients. Duodenal primary gastrinomas were found to have a significantly greater incidence of metastases (55%) and a significantly shorter disease-free interval (12 months) than pancreatic gastrinomas (22% and 84 months, respectively) suggesting that duodenal gastrinomas may be more malignant and not more frequently curable than pancreatic gastrinomas. Operations were performed with no deaths and 11% morbidity rate. Long-term follow-up showed that 50% of patients initially rendered disease free would develop recurrent disease by 5 years. Survival was excellent for all patients, and none died of malignant spread of the tumor or uncontrolled peptic ulcer disease, with a mean follow-up of 5 years. This finding is in contrast to patients who presented with metastatic disease on imaging studies and had a 20% 5-year survival rate. This study suggests that all patients with localized sporadic ZES can have the gastric acid hypersecretion managed medically, that overall survival of these patients is excellent, most (78%) can have all gastrinoma found and resected, and some (30%) will be cured (long-term disease-free survival).
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- Andersen D. K. Current diagnosis and management of Zollinger-Ellison syndrome. Ann Surg. 1989 Dec;210(6):685–703. doi: 10.1097/00000658-198912000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bardram L., Stadil F. Effects of omeprazole on acid secretion and acid-related symptoms in patients with Zollinger-Ellison syndrome. Scand J Gastroenterol Suppl. 1989;166:95–113. doi: 10.3109/00365528909091253. [DOI] [PubMed] [Google Scholar]
- Bonfils S., Landor J. H., Mignon M., Hervoir P. Results of surgical management in 92 consecutive patients with Zollinger-Ellison syndrome. Ann Surg. 1981 Dec;194(6):692–697. doi: 10.1097/00000658-198112000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carney J. A., Go V. L., Fairbanks V. F., Moore S. B., Alport E. C., Nora F. E. The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med. 1983 Dec;99(6):761–766. doi: 10.7326/0003-4819-99-6-761. [DOI] [PubMed] [Google Scholar]
- Cherner J. A., Doppman J. L., Norton J. A., Miller D. L., Krudy A. G., Raufman J. P., Collen M. J., Maton P. N., Gardner J. D., Jensen R. T. Selective venous sampling for gastrin to localize gastrinomas. A prospective assessment. Ann Intern Med. 1986 Dec;105(6):841–847. doi: 10.7326/0003-4819-105-6-841. [DOI] [PubMed] [Google Scholar]
- Clemett A. R., Park W. M. Arteriographic demonstration of pancreatic tumor in the Zollinger-Ellison syndrome. Radiology. 1967 Jan;88(1):32–34. doi: 10.1148/88.1.32. [DOI] [PubMed] [Google Scholar]
- Creutzfeldt W., Arnold R., Creutzfeldt C., Track N. S. Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). Hum Pathol. 1975 Jan;6(1):47–76. doi: 10.1016/s0046-8177(75)80109-2. [DOI] [PubMed] [Google Scholar]
- Damgaard-Petersen K., Stage J. G. CT scanning in patients with Zollinger-Ellison syndrome and carcinoid syndrome. Scand J Gastroenterol Suppl. 1979;53:117–122. [PubMed] [Google Scholar]
- Deutsch V., Adar R., Jacob E. T., Bank H., Mozes M. Angiographic diagnosis and differential diagnosis of islet-cell tumors. Am J Roentgenol Radium Ther Nucl Med. 1973 Sep;119(1):121–132. doi: 10.2214/ajr.119.1.121. [DOI] [PubMed] [Google Scholar]
- Deveney C. W., Deveney K. E., Stark D., Moss A., Stein S., Way L. W. Resection of gastrinomas. Ann Surg. 1983 Oct;198(4):546–553. doi: 10.1097/00000658-198310000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doppman J. L., Miller D. L., Chang R., Maton P. N., London J. F., Gardner J. D., Jensen R. T., Norton J. A. Gastrinomas: localization by means of selective intraarterial injection of secretin. Radiology. 1990 Jan;174(1):25–29. doi: 10.1148/radiology.174.1.2294556. [DOI] [PubMed] [Google Scholar]
- Dunnick N. R., Doppman J. L., Mills S. R., McCarthy D. M. Computed tomographic detection of nonbeta pancreatic islet cell tumors. Radiology. 1980 Apr;135(1):117–120. doi: 10.1148/radiology.135.1.6244605. [DOI] [PubMed] [Google Scholar]
- Dunnick N. R., Long J. A., Jr, Krudy A., Shawker T. H., Doppman J. L. Localizing insulinomas with combined radiographic methods. AJR Am J Roentgenol. 1980 Oct;135(4):747–752. doi: 10.2214/ajr.135.4.747. [DOI] [PubMed] [Google Scholar]
- ELLISON E. H., WILSON S. D. THE ZOLLINGER-ELLISON SYNDROME: RE-APPRAISAL AND EVALUATION OF 260 REGISTERED CASES. Ann Surg. 1964 Sep;160:512–530. doi: 10.1097/00000658-196409000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ekman L., Hansson E., Havu N., Carlsson E., Lundberg C. Toxicological studies on omeprazole. Scand J Gastroenterol Suppl. 1985;108:53–69. [PubMed] [Google Scholar]
- Fraker D. L., Norton J. A., Saeed Z. A., Maton P. N., Gardner J. D., Jensen R. T. A prospective study of perioperative and postoperative control of acid hypersecretion in patients with Zollinger-Ellison syndrome undergoing gastrinoma resection. Surgery. 1988 Dec;104(6):1054–1063. [PubMed] [Google Scholar]
- Friesen S. R. Treatment of the Zollinger-Ellison syndrome. A 25 year assessment. Am J Surg. 1982 Mar;143(3):331–338. doi: 10.1016/0002-9610(82)90102-7. [DOI] [PubMed] [Google Scholar]
- Friesen S. R. Tumors of the endocrine pancreas. N Engl J Med. 1982 Mar 11;306(10):580–590. doi: 10.1056/NEJM198203113061005. [DOI] [PubMed] [Google Scholar]
- Frucht H., Doppman J. L., Norton J. A., Miller D. L., Dwyer A. J., Frank J. A., Vinayek R., Maton P. N., Jensen R. T. Gastrinomas: comparison of MR imaging with CT, angiography, and US. Radiology. 1989 Jun;171(3):713–717. doi: 10.1148/radiology.171.3.2655004. [DOI] [PubMed] [Google Scholar]
- Frucht H., Howard J. M., Slaff J. I., Wank S. A., McCarthy D. M., Maton P. N., Vinayek R., Gardner J. D., Jensen R. T. Secretin and calcium provocative tests in the Zollinger-Ellison syndrome. A prospective study. Ann Intern Med. 1989 Nov 1;111(9):713–722. doi: 10.7326/0003-4819-111-9-713. [DOI] [PubMed] [Google Scholar]
- Frucht H., Maton P. N., Jensen R. T. Use of omeprazole in patients with Zollinger-Ellison syndrome. Dig Dis Sci. 1991 Apr;36(4):394–404. doi: 10.1007/BF01298865. [DOI] [PubMed] [Google Scholar]
- Frucht H., Norton J. A., London J. F., Vinayek R., Doppman J. L., Gardner J. D., Jensen R. T., Maton P. N. Detection of duodenal gastrinomas by operative endoscopic transillumination. A prospective study. Gastroenterology. 1990 Dec;99(6):1622–1627. doi: 10.1016/0016-5085(90)90466-e. [DOI] [PubMed] [Google Scholar]
- Harmon J. W., Norton J. A., Collin M. J., Krudy A. G., Shawker T. H., Doppman J. L., d'Avis J., Jensen R. T. Removal of gastrinomas for control of Zollinger-Ellison syndrome. Ann Surg. 1984 Oct;200(4):396–404. doi: 10.1097/00000658-198410000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard T. J., Zinner M. J., Stabile B. E., Passaro E., Jr Gastrinoma excision for cure. A prospective analysis. Ann Surg. 1990 Jan;211(1):9–14. doi: 10.1097/00000658-199001000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imamura M., Takahashi K., Adachi H., Minematsu S., Shimada Y., Naito M., Suzuki T., Tobe T., Azuma T. Usefulness of selective arterial secretin injection test for localization of gastrinoma in the Zollinger-Ellison syndrome. Ann Surg. 1987 Mar;205(3):230–239. doi: 10.1097/00000658-198703000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imamura M., Takahashi K., Isobe Y., Hattori Y., Satomura K., Tobe T. Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test. Ann Surg. 1989 Dec;210(6):710–718. doi: 10.1097/00000658-198912000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingemansson S., Larsson L. I., Lunderquist A., Stadil F. Pancreatic vein catheterization with gastrin assay in normal patients and in patients with the Zollinger-Ellison syndrome. Am J Surg. 1977 Nov;134(5):558–563. doi: 10.1016/0002-9610(77)90433-0. [DOI] [PubMed] [Google Scholar]
- Jensen R. T., Collen M. J., McArthur K. E., Howard J. M., Maton P. N., Cherner J. A., Gardner J. D. Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states. Am J Med. 1984 Nov 19;77(5B):90–105. [PubMed] [Google Scholar]
- Jensen R. T., Gardner J. D., Raufman J. P., Pandol S. J., Doppman J. L., Collen M. J. Zollinger-Ellison syndrome: current concepts and management. Ann Intern Med. 1983 Jan;98(1):59–75. doi: 10.7326/0003-4819-98-1-59. [DOI] [PubMed] [Google Scholar]
- Lambers C. B., Lind T., Moberg S., Jansen J. B., Olbe L. Omeprazole in Zollinger-Ellison syndrome. Effects of a single dose and of long-term treatment in patients resistant to histamine H2-receptor antagonists. N Engl J Med. 1984 Mar 22;310(12):758–761. doi: 10.1056/NEJM198403223101205. [DOI] [PubMed] [Google Scholar]
- Malagelada J. R., Edis A. J., Adson M. A., van Heerden J. A., Go V. L. Medical and surgical options in the management of patients with gastrinoma. Gastroenterology. 1983 Jun;84(6):1524–1532. [PubMed] [Google Scholar]
- Maton P. N., Frucht H., Vinayek R., Wank S. A., Gardner J. D., Jensen R. T. Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: a prospective study. Gastroenterology. 1988 Feb;94(2):294–299. doi: 10.1016/0016-5085(88)90415-5. [DOI] [PubMed] [Google Scholar]
- Maton P. N., Gardner J. D., Jensen R. T. Recent advances in the management of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterol Clin North Am. 1989 Dec;18(4):847–863. [PubMed] [Google Scholar]
- Maton P. N., Miller D. L., Doppman J. L., Collen M. J., Norton J. A., Vinayek R., Slaff J. I., Wank S. A., Gardner J. D., Jensen R. T. Role of selective angiography in the management of patients with Zollinger-Ellison syndrome. Gastroenterology. 1987 Apr;92(4):913–918. doi: 10.1016/0016-5085(87)90964-4. [DOI] [PubMed] [Google Scholar]
- McArthur K. E., Collen M. J., Maton P. N., Cherner J. A., Howard J. M., Ciarleglio C. A., Cornelius M. J., Jensen R. T., Gardner J. D. Omeprazole: effective, convenient therapy for Zollinger-Ellison syndrome. Gastroenterology. 1985 Apr;88(4):939–944. doi: 10.1016/s0016-5085(85)80011-1. [DOI] [PubMed] [Google Scholar]
- McCarthy D. M. Report on the United States experience with cimetidine in Zollinger-Ellision syndrome and other hypersecretory states. Gastroenterology. 1978 Feb;74(2 Pt 2):453–458. [PubMed] [Google Scholar]
- McCarthy D. M. The place of surgery in the Zollinger-Ellison syndrome. N Engl J Med. 1980 Jun 12;302(24):1344–1347. doi: 10.1056/NEJM198006123022404. [DOI] [PubMed] [Google Scholar]
- McGuigan J. E., Trudeau W. L. Immunochemical measurement of elevated levels of gastrin in the serum of patients with pancreatic tumors of the Zollinger-Ellison variety. N Engl J Med. 1968 Jun 13;278(24):1308–1313. doi: 10.1056/NEJM196806132782402. [DOI] [PubMed] [Google Scholar]
- McGuigan J. E., Wolfe M. M. Secretin injection test in the diagnosis of gastrinoma. Gastroenterology. 1980 Dec;79(6):1324–1331. [PubMed] [Google Scholar]
- Mignon M., Ruszniewski P., Haffar S., Rigaud D., Rene E., Bonfils S. Current approach to the management of tumoral process in patients with gastrinoma. World J Surg. 1986 Aug;10(4):703–710. doi: 10.1007/BF01655562. [DOI] [PubMed] [Google Scholar]
- Norton J. A., Cornelius M. J., Doppman J. L., Maton P. N., Gardner J. D., Jensen R. T. Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. Surgery. 1987 Dec;102(6):958–966. [PubMed] [Google Scholar]
- Norton J. A., Cromack D. T., Shawker T. H., Doppman J. L., Comi R., Gorden P., Maton P. N., Gardner J. D., Jensen R. T. Intraoperative ultrasonographic localization of islet cell tumors. A prospective comparison to palpation. Ann Surg. 1988 Feb;207(2):160–168. doi: 10.1097/00000658-198802000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norton J. A., Doppman J. L., Collen M. J., Harmon J. W., Maton P. N., Gardner J. D., Jensen R. T. Prospective study of gastrinoma localization and resection in patients with Zollinger-Ellison syndrome. Ann Surg. 1986 Oct;204(4):468–479. doi: 10.1097/00000658-198610000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norton J. A., Jensen R. T. Unresolved surgical issues in the management of patients with Zollinger-Ellison syndrome. World J Surg. 1991 Jan-Feb;15(1):151–159. doi: 10.1007/BF01658992. [DOI] [PubMed] [Google Scholar]
- Norton J. A., Sugarbaker P. H., Doppman J. L., Wesley R. A., Maton P. N., Gardner J. D., Jensen R. T. Aggressive resection of metastatic disease in selected patients with malignant gastrinoma. Ann Surg. 1986 Apr;203(4):352–359. doi: 10.1097/00000658-198604000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raufman J. P., Collins S. M., Pandol S. J., Korman L. Y., Collen M. J., Cornelius M. J., Feld M. K., McCarthy D. M., Gardner J. D., Jensen R. T. Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome. Gastroenterology. 1983 Jan;84(1):108–113. [PubMed] [Google Scholar]
- Richardson C. T., Peters M. N., Feldman M., McClelland R. N., Walsh J. H., Cooper K. A., Willeford G., Dickerman R. M., Fordtran J. S. Treatment of Zollinger-Ellison syndrome with exploratory laparotomy, proximal gastric vagotomy, and H2-receptor antagonists. A prospective study. Gastroenterology. 1985 Aug;89(2):357–367. doi: 10.1016/0016-5085(85)90337-3. [DOI] [PubMed] [Google Scholar]
- Roche A., Raisonnier A., Gillon-Savouret M. C. Pancreatic venous sampling and arteriography in localizing insulinomas and gastrinomas: procedure and results in 55 cases. Radiology. 1982 Dec;145(3):621–627. doi: 10.1148/radiology.145.3.6292994. [DOI] [PubMed] [Google Scholar]
- Saeed Z. A., Norton J. A., Frank W. O., Young M. D., Maton P. N., Gardner J. D., Jensen R. T. Parenteral antisecretory drug therapy in patients with Zollinger-Ellison syndrome. Gastroenterology. 1989 Jun;96(6):1393–1402. doi: 10.1016/0016-5085(89)90504-0. [DOI] [PubMed] [Google Scholar]
- Sheppard B. C., Norton J. A., Doppman J. L., Maton P. N., Gardner J. D., Jensen R. T. Management of islet cell tumors in patients with multiple endocrine neoplasia: a prospective study. Surgery. 1989 Dec;106(6):1108–1118. [PubMed] [Google Scholar]
- Solcia E., Capella C., Buffa R., Usellini L., Frigerio B., Fontana P. Endocrine cells of the gastrointestinal tract and related tumors. Pathobiol Annu. 1979;9:163–204. [PubMed] [Google Scholar]
- Solcia E., Capella C., Fiocca R., Cornaggia M., Bosi F. The gastroenteropancreatic endocrine system and related tumors. Gastroenterol Clin North Am. 1989 Dec;18(4):671–693. [PubMed] [Google Scholar]
- Stabile B. E., Morrow D. J., Passaro E., Jr The gastrinoma triangle: operative implications. Am J Surg. 1984 Jan;147(1):25–31. doi: 10.1016/0002-9610(84)90029-1. [DOI] [PubMed] [Google Scholar]
- Stabile B. E., Passaro E., Jr Benign and malignant gastrinoma. Am J Surg. 1985 Jan;149(1):144–150. doi: 10.1016/s0002-9610(85)80024-6. [DOI] [PubMed] [Google Scholar]
- Thompson J. C., Lewis B. G., Wiener I., Townsend C. M., Jr The role of surgery in the Zollinger-Ellison syndrome. Ann Surg. 1983 May;197(5):594–607. doi: 10.1097/00000658-198305000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson N. W., Vinik A. I., Eckhauser F. E. Microgastrinomas of the duodenum. A cause of failed operations for the Zollinger-Ellison syndrome. Ann Surg. 1989 Apr;209(4):396–404. doi: 10.1097/00000658-198904000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vinayek R., Frucht H., Chiang H. C., Maton P. N., Gardner J. D., Jensen R. T. Zollinger-Ellison syndrome. Recent advances in the management of the gastrinoma. Gastroenterol Clin North Am. 1990 Mar;19(1):197–217. [PubMed] [Google Scholar]
- Vinayek R., Frucht H., London J. F., Miller L. S., Stark H. A., Norton J. A., Cederberg C., Jensen R. T., Gardner J. D., Maton P. N. Intravenous omeprazole in patients with Zollinger-Ellison syndrome undergoing surgery. Gastroenterology. 1990 Jul;99(1):10–16. doi: 10.1016/0016-5085(90)91223-s. [DOI] [PubMed] [Google Scholar]
- Vinayek R., Howard J. M., Maton P. N., Wank S. A., Slaff J. I., Gardner J. D., Jensen R. T. Famotidine in the therapy of gastric hypersecretory states. Am J Med. 1986 Oct 24;81(4B):49–59. doi: 10.1016/0002-9343(86)90600-5. [DOI] [PubMed] [Google Scholar]
- Vogel S. B., Wolfe M. M., McGuigan J. E., Hawkins I. F., Jr, Howard R. J., Woodward E. R. Localization and resection of gastrinomas in Zollinger-Ellison syndrome. Ann Surg. 1987 May;205(5):550–556. doi: 10.1097/00000658-198705000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wank S. A., Doppman J. L., Miller D. L., Collen M. J., Maton P. N., Vinayek R., Slaff J. I., Norton J. A., Gardner J. D., Jensen R. T. Prospective study of the ability of computed axial tomography to localize gastrinomas in patients with Zollinger-Ellison syndrome. Gastroenterology. 1987 Apr;92(4):905–912. doi: 10.1016/0016-5085(87)90963-2. [DOI] [PubMed] [Google Scholar]
- Wise S. R., Johnson J., Sparks J., Carey L. C., Ellison E. C. Gastrinoma: the predictive value of preoperative localization. Surgery. 1989 Dec;106(6):1087–1093. [PubMed] [Google Scholar]
- Wolfe M. M., Alexander R. W., McGuigan J. E. Extrapancreatic, extraintestinal gastrinoma: effective treatment by surgery. N Engl J Med. 1982 Jun 24;306(25):1533–1536. doi: 10.1056/NEJM198206243062506. [DOI] [PubMed] [Google Scholar]
- Wolfe M. M., Jensen R. T. Zollinger-Ellison syndrome. Current concepts in diagnosis and management. N Engl J Med. 1987 Nov 5;317(19):1200–1209. doi: 10.1056/NEJM198711053171907. [DOI] [PubMed] [Google Scholar]
- ZOLLINGER R. M., ELLISON E. H. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955 Oct;142(4):709-23; discussion, 724-8. [PMC free article] [PubMed] [Google Scholar]
- Zollinger R. M., Ellison E. C., Fabri P. J., Johnson J., Sparks J., Carey L. C. Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal. Ann Surg. 1980 Sep;192(3):422–430. doi: 10.1097/00000658-198009000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zollinger R. M. Gastrinoma: factors influencing prognosis. Surgery. 1985 Jan;97(1):49–54. [PubMed] [Google Scholar]
- Zollinger R. M., Martin E. W., Jr, Carey L. C., Sparks J., Minton J. P. Observations on the postoperative tumor growth behavior of certain islet cell tumors. Ann Surg. 1976 Oct;184(4):525–530. doi: 10.1097/00000658-197610000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Schrenck T., Howard J. M., Doppman J. L., Norton J. A., Maton P. N., Smith F. P., Vinayek R., Frucht H., Wank S. A., Gardner J. D. Prospective study of chemotherapy in patients with metastatic gastrinoma. Gastroenterology. 1988 Jun;94(6):1326–1334. doi: 10.1016/0016-5085(88)90670-1. [DOI] [PubMed] [Google Scholar]