Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1998 Aug;228(2):228–238. doi: 10.1097/00000658-199808000-00013

Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome.

H R Alexander 1, D L Fraker 1, J A Norton 1, D L Bartlett 1, L Tio 1, S B Benjamin 1, J L Doppman 1, S U Goebel 1, J Serrano 1, F Gibril 1, R T Jensen 1
PMCID: PMC1191465  PMID: 9712569

Abstract

OBJECTIVE: To determine the relative abilities of somatostatin receptor scintigraphy (SRS) and conventional imaging studies (computed tomography, magnetic resonance imaging, ultrasound, angiography) to localize gastrinomas before surgery in patients with Zollinger-Ellison syndrome (ZES) subsequently found at surgery, and to determine the effect of SRS on the disease-free rate. SUMMARY BACKGROUND DATA: Recent studies demonstrate that SRS is the most sensitive imaging modality for localizing neuroendocrine tumors such as gastrinomas. Because of conflicting results in small series, it is unclear in ZES whether SRS will alter the disease-free rate, which gastrinomas are not detected, what factors contribute to failure to detect a gastrinoma, or whether the SRS result should be used to determine operability in patients without hepatic metastases, as recently recommended by some investigators. METHODS: Thirty-five consecutive patients with ZES undergoing 37 exploratory laparotomies for possible cure were prospectively studied. All had SRS and conventional imaging studies before surgery. Imaging results were determined by an independent investigator depending on surgical findings. All patients underwent an identical surgical protocol (palpation after an extensive Kocher maneuver, ultrasound during surgery, duodenal transillumination, and 3 cm duodenotomy) and postoperative assessment of disease status (fasting gastrin, secretin test imaging within 2 weeks, at 3 to 6 months, and yearly), as used in pre-SRS studies previously. RESULTS: Gastrinomas were detected in all patients at each surgery. Seventy-four gastrinomas were found: 22 duodenal, 8 pancreatic, 3 primaries in other sites, and 41 lymph node metastases. The relative detection order on a per-patient or per-lesion basis was SRS > angiography, magnetic resonance imaging, computed tomography > ultrasound. On a per-lesion basis, SRS had greater sensitivity than all conventional studies combined. SRS missed one third of all lesions found at surgery. SRS detected 30% of gastrinomas < or =1.1 cm, 64% of those 1.1 to 2 cm, and 96% of those >2 cm and missed primarily small duodenal tumors. Tumor size correlated closely with SRS rate of detection. SRS did not increase the disease-free rate immediately after surgery or at 2 years mean follow-up. CONCLUSIONS: SRS is the most sensitive preoperative imaging study for extrahepatic gastrinomas in patients with ZES and should replace conventional imaging studies as the preoperative study of choice. Negative results of SRS for localizing extrahepatic gastrinomas should not be used to decide operability, because a surgical procedure will detect 33% more gastrinomas than SRS. SRS does not increase the disease-free rate. In the future, more sensitive methods to detect small gastrinomas, especially in the duodenum and in periduodenal lymph nodes, or more extensive surgery will be needed to improve the postoperative disease-free rate in ZES.

Full text

PDF
228

Images in this article

233Figure 1.
on p.233
234Figure 2.
on p.234

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arbab A. S., Koizumi K., Hemmi A., Toyama K., Arai T., Yoshitomi T., Araki T. Tc-99m-MIBI scintigraphy for detecting parathyroid adenoma and hyperplasia. Ann Nucl Med. 1997 Feb;11(1):45–49. doi: 10.1007/BF03164759. [DOI] [PubMed] [Google Scholar]
  2. Benya R. V., Metz D. C., Venzon D. J., Fishbeyn V. A., Strader D. B., Orbuch M., Jensen R. T. Zollinger-Ellison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia-type I. Am J Med. 1994 Nov;97(5):436–444. doi: 10.1016/0002-9343(94)90323-9. [DOI] [PubMed] [Google Scholar]
  3. Bergenfelz A., Tennvall J., Valdermarsson S., Lindblom P., Tibblin S. Sestamibi versus thallium subtraction scintigraphy in parathyroid localization: a prospective comparative study in patients with predominantly mild primary hyperparathyroidism. Surgery. 1997 Jun;121(6):601–605. doi: 10.1016/s0039-6060(97)90046-5. [DOI] [PubMed] [Google Scholar]
  4. Cadiot G., Lebtahi R., Sarda L., Bonnaud G., Marmuse J. P., Vissuzaine C., Ruszniewski P., Le Guludec D., Mignon M. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D'etude Du Syndrome De Zollinger-Ellison. Gastroenterology. 1996 Oct;111(4):845–854. doi: 10.1016/s0016-5085(96)70052-5. [DOI] [PubMed] [Google Scholar]
  5. Delcore R., Friesen S. R. The place for curative surgical procedures in the treatment of sporadic and familial Zollinger-Ellison syndrome. Curr Opin Gen Surg. 1994:69–76. [PubMed] [Google Scholar]
  6. 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]
  7. Fishbeyn V. A., Norton J. A., Benya R. V., Pisegna J. R., Venzon D. J., Metz D. C., Jensen R. T. Assessment and prediction of long-term cure in patients with the Zollinger-Ellison syndrome: the best approach. Ann Intern Med. 1993 Aug 1;119(3):199–206. doi: 10.7326/0003-4819-119-3-199308010-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fraker D. L., Norton J. A., Alexander H. R., Venzon D. J., Jensen R. T. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann Surg. 1994 Sep;220(3):320–330. doi: 10.1097/00000658-199409000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Gibril F., Reynolds J. C., Doppman J. L., Chen C. C., Venzon D. J., Termanini B., Weber H. C., Stewart C. A., Jensen R. T. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study. Ann Intern Med. 1996 Jul 1;125(1):26–34. doi: 10.7326/0003-4819-125-1-199607010-00005. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Jaskowiak N. T., Fraker D. L., Alexander H. R., Norton J. A., Doppman J. L., Jensen R. T. Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome? Surgery. 1996 Dec;120(6):1055–1063. doi: 10.1016/s0039-6060(96)80055-9. [DOI] [PubMed] [Google Scholar]
  14. Kisker O., Weinel R. J., Geks J., Zacara F., Joseph K., Rothmund M. Value of somatostatin receptor scintigraphy for preoperative localization of carcinoids. World J Surg. 1996 Feb;20(2):162–167. doi: 10.1007/s002689900025. [DOI] [PubMed] [Google Scholar]
  15. Krenning E. P., Kooij P. P., Pauwels S., Breeman W. A., Postema P. T., De Herder W. W., Valkema R., Kwekkeboom D. J. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion. 1996;57 (Suppl 1):57–61. doi: 10.1159/000201398. [DOI] [PubMed] [Google Scholar]
  16. Krenning E. P., Kwekkeboom D. J., Bakker W. H., Breeman W. A., Kooij P. P., Oei H. Y., van Hagen M., Postema P. T., de Jong M., Reubi J. C. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993 Aug;20(8):716–731. doi: 10.1007/BF00181765. [DOI] [PubMed] [Google Scholar]
  17. Krenning E. P., Kwekkeboom D. J., Oei H. Y., de Jong R. J., Dop F. J., Reubi J. C., Lamberts S. W. Somatostatin-receptor scintigraphy in gastroenteropancreatic tumors. An overview of European results. Ann N Y Acad Sci. 1994 Sep 15;733:416–424. doi: 10.1111/j.1749-6632.1994.tb17291.x. [DOI] [PubMed] [Google Scholar]
  18. Lebtahi R., Cadiot G., Sarda L., Daou D., Faraggi M., Petegnief Y., Mignon M., le Guludec D. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med. 1997 Jun;38(6):853–858. [PubMed] [Google Scholar]
  19. London J. F., Shawker T. H., Doppman J. L., Frucht H. H., Vinayek R., Stark H. A., Miller L. S., Miller D. L., Norton J. A., Jensen R. T. Zollinger-Ellison syndrome: prospective assessment of abdominal US in the localization of gastrinomas. Radiology. 1991 Mar;178(3):763–767. doi: 10.1148/radiology.178.3.1994415. [DOI] [PubMed] [Google Scholar]
  20. MacFarlane M. P., Fraker D. L., Alexander H. R., Norton J. A., Lubensky I., Jensen R. T. Prospective study of surgical resection of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery. 1995 Dec;118(6):973–980. doi: 10.1016/s0039-6060(05)80102-3. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Meko J. B., Doherty G. M., Siegel B. A., Norton J. A. Evaluation of somatostatin-receptor scintigraphy for detecting neuroendocrine tumors. Surgery. 1996 Dec;120(6):975–984. doi: 10.1016/s0039-6060(96)80043-2. [DOI] [PubMed] [Google Scholar]
  23. Metz D. C., Pisegna J. R., Fishbeyn V. A., Benya R. V., Jensen R. T. Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. World J Surg. 1993 Jul-Aug;17(4):468–480. doi: 10.1007/BF01655106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Norton J. A. Advances in the management of Zollinger-Ellison syndrome. Adv Surg. 1994;27:129–159. [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Norton J. A., Doppman J. L., Jensen R. T. Curative resection in Zollinger-Ellison syndrome. Results of a 10-year prospective study. Ann Surg. 1992 Jan;215(1):8–18. doi: 10.1097/00000658-199201000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Pisegna J. R., Doppman J. L., Norton J. A., Metz D. C., Jensen R. T. Prospective comparative study of ability of MR imaging and other imaging modalities to localize tumors in patients with Zollinger-Ellison syndrome. Dig Dis Sci. 1993 Jul;38(7):1318–1328. doi: 10.1007/BF01296084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reubi J. C., Laissue J., Waser B., Horisberger U., Schaer J. C. Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann N Y Acad Sci. 1994 Sep 15;733:122–137. doi: 10.1111/j.1749-6632.1994.tb17262.x. [DOI] [PubMed] [Google Scholar]
  32. Ruszniewski P., Amouyal P., Amouyal G., Grangé J. D., Mignon M., Bouché O., Bernades P. Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. Surgery. 1995 Jun;117(6):629–635. doi: 10.1016/s0039-6060(95)80005-0. [DOI] [PubMed] [Google Scholar]
  33. Rösch T., Lightdale C. J., Botet J. F., Boyce G. A., Sivak M. V., Jr, Yasuda K., Heyder N., Palazzo L., Dancygier H., Schusdziarra V. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. 1992 Jun 25;326(26):1721–1726. doi: 10.1056/NEJM199206253262601. [DOI] [PubMed] [Google Scholar]
  34. Schirmer W. J., Melvin W. S., Rush R. M., O'Dorisio T. M., Pozderac R. V., Olsen J. O., Ellison E. C. Indium-111-pentetreotide scanning versus conventional imaging techniques for the localization of gastrinoma. Surgery. 1995 Dec;118(6):1105–1114. doi: 10.1016/s0039-6060(05)80121-7. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Sugg S. L., Norton J. A., Fraker D. L., Metz D. C., Pisegna J. R., Fishbeyn V., Benya R. V., Shawker T. H., Doppman J. L., Jensen R. T. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann Surg. 1993 Aug;218(2):138–144. doi: 10.1097/00000658-199308000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Termanini B., Gibril F., Doppman J. L., Reynolds J. C., Stewart C. A., Sutliff V. E., Venzon D. J., Jensen R. T. Distinguishing small hepatic hemangiomas from vascular liver metastases in gastrinoma: use of a somatostatin-receptor scintigraphic agent. Radiology. 1997 Jan;202(1):151–158. doi: 10.1148/radiology.202.1.8988205. [DOI] [PubMed] [Google Scholar]
  38. Termanini B., Gibril F., Reynolds J. C., Doppman J. L., Chen C. C., Stewart C. A., Sutliff V. E., Jensen R. T. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology. 1997 Feb;112(2):335–347. doi: 10.1053/gast.1997.v112.pm9024287. [DOI] [PubMed] [Google Scholar]
  39. Thom A. K., Norton J. A., Axiotis C. A., Jensen R. T. Location, incidence, and malignant potential of duodenal gastrinomas. Surgery. 1991 Dec;110(6):1086–1093. [PubMed] [Google Scholar]
  40. Thompson N. W., Czako P. F., Fritts L. L., Bude R., Bansal R., Nostrant T. T., Scheiman J. M. Role of endoscopic ultrasonography in the localization of insulinomas and gastrinomas. Surgery. 1994 Dec;116(6):1131–1138. [PubMed] [Google Scholar]
  41. Udelsman R., Yeo C. J., Hruban R. H., Pitt H. A., Niederhuber J. E., Coleman J., Cameron J. L. Pancreaticoduodenectomy for selected pancreatic endocrine tumors. Surg Gynecol Obstet. 1993 Sep;177(3):269–278. [PubMed] [Google Scholar]
  42. 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]
  43. Weber H. C., Venzon D. J., Lin J. T., Fishbein V. A., Orbuch M., Strader D. B., Gibril F., Metz D. C., Fraker D. L., Norton J. A. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology. 1995 Jun;108(6):1637–1649. doi: 10.1016/0016-5085(95)90124-8. [DOI] [PubMed] [Google Scholar]
  44. Weinel R. J., Neuhaus C., Stapp J., Klotter H. J., Trautmann M. E., Joseph K., Arnold R., Rothmund M. Preoperative localization of gastrointestinal endocrine tumors using somatostatin-receptor scintigraphy. Ann Surg. 1993 Nov;218(5):640–645. doi: 10.1097/00000658-199321850-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Woltering E. A., Barrie R., O'Dorisio T. M., O'Dorisio M. S., Nance R., Cook D. M. Detection of occult gastrinomas with iodine 125-labeled lanreotide and intraoperative gamma detection. Surgery. 1994 Dec;116(6):1139–1147. [PubMed] [Google Scholar]
  46. Zimmer T., Stölzel U., Bäder M., Koppenhagen K., Hamm B., Buhr H., Riecken E. O., Wiedenmann B. Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut. 1996 Oct;39(4):562–568. doi: 10.1136/gut.39.4.562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. de Kerviler E., Cadiot G., Lebtahi R., Faraggi M., Le Guludec D., Mignon M. Somatostatin receptor scintigraphy in forty-eight patients with the Zollinger-Ellison syndrome. GRESZE: Groupe d'Etude du Syndrome de Zollinger-Ellison. Eur J Nucl Med. 1994 Nov;21(11):1191–1197. doi: 10.1007/BF00182352. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES