Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas

British Journal of Surgery

Volumn 94, Issue 11, 2007, Pages 1331-1341

  Fendrich, V ^a   Langer, P ^a   Waldmann, J ^a   Bartsch, D K ^b   Rothmund, M ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b OWL University   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; CHROMOGRANIN A; DOXORUBICIN; FLUOROURACIL; OCTREOTIDE; PANTOPRAZOLE; PROTON PUMP INHIBITOR; STOMACH SECRETION INHIBITOR; STREPTOZOCIN;

ABDOMINAL PAIN; BIOCHEMISTRY; CANCER SURGERY; CANCER SURVIVAL; CLINICAL FEATURE; DISEASE ASSOCIATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG WITHDRAWAL; DUODENUM; DUODENUM TUMOR; ECHOGRAPHY; GASTRINOMA; GENE MUTATION; HUMAN; INFORMATION PROCESSING; LIVER METASTASIS; LIVER RESECTION; MEDLINE; MULTIPLE ENDOCRINE NEOPLASIA; PANCREAS; PANCREAS RESECTION; PANCREAS TUMOR; PANCREATICODUODENECTOMY; PRIORITY JOURNAL; PROGNOSIS; PYLORUS; RADIOFREQUENCY ABLATION; REVIEW; STOMACH ACID SECRETION; SURGICAL TECHNIQUE; SURVIVAL RATE; TREATMENT RESPONSE; TUMOR LOCALIZATION; ZOLLINGER ELLISON SYNDROME;

DUODENAL NEOPLASMS; GASTRINOMA; HUMANS; MULTIPLE ENDOCRINE NEOPLASIA TYPE 1; PANCREATIC NEOPLASMS; PROGNOSIS;

EID: 36349020246     PISSN: 00071323     EISSN: 13652168     Source Type: Journal    
DOI: 10.1002/bjs.5987     Document Type: Review

References (96)

1. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 1955; 142: 709-723.
2. McGuigan JE, Trudeau WL. 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; 278: 1308-1313.
3. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1 (MEN1). Science 1997; 276: 404-407.
4. Zhuang Z, Vortmeyer AO, Pack S, Huang S, Pham TA, Wang C et al. Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas. Cancer Res 1997; 57: 4682-4686.
5. Wilkinson S, Teh BT, Davey KR, McArdle JP, Young M, Shepherd JJ. Cause of death in multiple endocrine neoplasia type 1. Arch Surg 1993; 128: 683-690.
6. Doherty GM, Olson JA, Frisella MM, Lairmore TC, Wells SA, Norton JA. Lethality of multiple endocrine neoplasia type I. World J Surg 1998; 22: 581-587.
7. Skogseid B, Eriksson B, Lundqvist G, Lorelius LE, Rastad J, Wide L et al. Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab 1991; 73: 281-287.
8. Anlauf M, Perren A, Henopp T, Rudolf T, Garbrecht N, Schmitt A et al. Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions. Gut 2007; 56: 637-644.
9. Serrano J, Goebel SU, Peghini PL, Lubensky IA, Gibril F, Jensen RT. Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab 2000; 85: 4146-4156.
10. Kaplan EL, Horvath K, Udekwu A, Straus F, Schark C, Ferguson DJ et al. Gastrinomas: a 42-year experience. World J Surg 1990; 14: 365-375.
11. Mignon M, Cadiot G. Diagnostic and therapeutic criteria in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. J Intern Med 1998; 243: 489-494.
12. Roy PK, Venzon DJ, Shojamanesh H, Abou-Saif A, Peghini P, Doppman JL et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine 2000; 79: 379-411.
13. Hoffmann KM, Gibril F, Entsuah LK, Serrano J, Jensen RT. Patients with multiple endocrine neoplasia type 1 with gastrinomas have an increased risk of severe esophageal disease including stricture and the premalignant condition, Barrett's esophagus. J Clin Endocrinol Metab 2006; 91: 204-212.
14. Gibril F, Schumann M, Pace A, Jensen RT. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore) 2004; 83: 43-83.
15. Fendrich V, Bartsch DK, Langer P, Zielke A, Rothmund M. Zollinger-Ellison syndrome. Chirurg 2005; 76: 217-226.
16. Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT. Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2229 cases from the literature. Medicine (Baltimore) 2006; 85: 295-330.
17. Dhillo WS, Jayasena CN, Lewis CJ, Martin NM, Tang KC, Meeran K et al. Plasma gastrin measurement cannot be used to diagnose a gastrinoma in patients on either proton pump inhibitors or histamine type-2 receptor antagonists. Ann Clin Biochem 2006; 43: 153-155.
18. Berna MJ, Hoffmann KM, Long SH, Serrano J, Gibril F, Jensen RT. Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. Evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine (Baltimore) 2006; 85: 331-364.
19. Fishbeyn VA, Norton JA, Benya RV, Pisegna JR, Venzon DJ, Metz DC et al. Assessment and prediction of long-term cure in patients with the Zollinger-Ellison syndrome: the best approach. Ann Intern Med 1993; 119: 199-206.
20. Frucht H, Howard JM, Slaff JI, Wank SA, McCarthy DM, Maton PN et al. Secretin and calcium provocative tests in the Zollinger-Ellison syndrome. A prospective study. Ann Intern Med 1989; 111: 713-722.
21. Wada M, Komoto I, Doi R, Imamura M. Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma. World J Surg 2002; 26: 1291-1296.
22. Goebel SU, Serrano J, Yu F, Gibril F, Venzon DJ, Jensen RT. Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas. Cancer 1999; 85: 1470-1483.
23. Nikou GC, Toubanakis C, Nikolaou P, Giannatou E, Marinou K, Safioleas M et al. Gastrinomas associated with MEN-1 syndrome: new insights for the diagnosis and management in a series of 11 patients. Hepatogastroenterology 2005; 52: 1668-1676.
24. Abou-Saif A, Gibril F, Ojeaburu JV, Bashir S, Entsuah LK, Asgharian B et al. Prospective study of the ability of serial measurements of serum chromogranin A and gastrin to detect changes in tumor burden in patients with gastrinomas. Cancer 2001; 98: 249-261.
25. Stabile BE, Morrow DJ, Passaro E Jr. The gastrinoma triangle: operative implications. Am J Surg 1984; 147: 25-31.
26. Hoffmann KM, Furukawa M, Jensen RT. Duodenal neuroendocrine tumors: classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005; 19: 675-697.
27. Sugg SL, Norton JA, Fraker DL, Metz DC, Pisegna JR, Fishbeyn V et al. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann Surg 1993; 218: 138-144.
28. Norton JA, Fraker DL, Alexander HR, Venzon DJ, Doppman JL, Serrano J et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341: 635-644.
29. Kisker O, Bastian D, Bartsch D, Nies C, Rothmund M. Localization, malignant potential and surgical management of gastrinomas. World J Surg 1998; 22: 651-657.
30. Zimmer T, Scherübl H, Faiss S, Stolzel U, Riecken EO, Wiedenmann B. Endoscopic ultrasonography of neuroendocrine tumours. Digestion 2000; 62(Suppl 1): 45-50.
31. Anderson MA, Carpenter S, Thompson NW, Nostrant TT, Elta GH, Scheiman JM. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol 2000; 95: 2271-2277.
32. Gibril F, Reynolds JC, Doppmann JL, Chen CC, Venzon DJ, Termanini B et al. 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; 125: 26-34.
33. 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; 210: 710-718.
34. Vinik AL, Moattari AR, Cho K, Thompson N. Transhepatic portal vein catheterization for localization of sporadic and MEN gastrinomas: a ten-year experience. Surgery 1990; 107: 246-255.
35. Palazzo L, Roseau G, Chaussade S, Salmeron M, Gaudric M, Paolaggi JA. [Pancreatic endocrine tumors: contribution of ultrasound endoscopy in the diagnosis of localization.] Ann Chir 1993; 47: 419-424.
36. Rösch T, Lightdale CJ, Botet JF, Boyce GA, Sivak MV, Yasuda K et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med 1992; 326: 1721-1726.
37. Ruszniewski P, Amouyal P, Amouyal G, Grange JD, Mignon M, Bouche O et al. Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. Surgery 1995; 117: 629-635.
38. Krenning EP, Kwekkeboom DJ, Oei HY, de Jong RJ, Dop FJ, de Herder WW et al. Somatostatin receptor scintigraphy in carcinoids, gastrinomas and Cushing's syndrome. Digestion 1994; 55(Suppl 3): 54-59.
39. Proye C, Malvaux P, Pattou F, Filoche B, Godchaux JM, Maunoury V et al. Noninvasive imaging of insulinomas and gastrinomas with endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery 1998; 124: 1134-1143.
40. Gibril F, Doppman JL, Reynolds JC, Chen CC, Sutliff VE, Yu F et al. Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect of their detection on management. J Clin Oncol 1998; 16: 1040-1053.
41. Alexander HR, Fraker DL, Norton JA, Bartlett DL, Tio L, Benjamin SB et al. Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome. Ann Surg 1998; 228: 228-238.
42. Termanini B, Gibril F, Reynolds JC, Doppman JL, Chen CC, Stewart CA et al. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology 1997; 112: 335-347.
43. Gibril F, Doppman JL, Chang R, Weber HC, Termanini B, Jensen RT. Metastatic gastrinomas: localization with selective arterial injection of secretin. Radiology 1996; 198: 77-84.
44. Cadiot G, Lebtahi R, Sarda L, Bonnaud G, Marmuse JP, Vissuzaine C et al. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe d'Etude du Syndrome de Zollinger-Ellison. Gastroenterology 1996; 111: 845-854.
45. Imamura M, Takahashi K. Use of selective arterial secretin injection test to guide surgery in patients with Zollinger-Ellison syndrome. World J Surg 1993; 17: 433-438.
46. Miller DL, Doppman JL, Metz DC, Maton PN, Norton JA, Jensen RT. Zollinger-Ellison syndrome: technique, results, and complications of portal venous sampling. Radiology 1992; 182: 235-241.
47. Frucht H, Norton JA, London JF, Vinayek R, Doppman JL, Gardner JD et al. Detection of duodenal gastrinomas by operative endoscopic transillumination. A prospective study. Gastroenterology 1990; 99: 1622-1627.
48. Norton JA, Alexander HR, Fraker DL, Venzon DJ, Gibril F, Jensen RT. Does the use of routine duodenotomy (DUODX) affect rate of cure, development of liver metastases, or survival in patients with Zollinger-Ellison syndrome? Ann Surg 2004; 239: 617-625.
49. Skogseid B, Grama D, Rastad J, Eriksson B, Lindgren PG, Ahlstrom H et al. Operative tumour yield obviates preoperative pancreatic localization in multiple endocrine neoplasia type 1. J Intern Med 1996; 238: 281-288.
50. Langer P, Kann PH, Fendrich V, Richter G, Diehl S, Rothmund M et al. Prospective evaluation of imaging procedures for the detection of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. World J Surg 2004; 28: 1317-1322.
51. Kann PH, Balakina E, Ivan D, Bartsch DK, Meyer S, Klose KJ et al. Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. Endocr Relat Cancer 2006; 13: 1195-1202.
52. Kato M, Imamura M, Hosotani R, Shimada Y, Doi R, Itami A et al. Curative resection of microgastrinomas based on the intraoperative secretin test. World J Surg 2000; 24: 1425-1430.
53. Weber HC, Venzon DJ, Lin JT, Fishbein VA, Orbuch M, Strader DB et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology 1995; 108: 1637-1649.
54. Imamura M, Kanda M, Takahashi K, Shimada Y, Miyahara T, Wagata T et al. Clinicopathological characteristics of duodenal microgastrinomas. World J Surg 1992; 16: 703-709.
55. Yu F, Venzon DJ, Serrano J, Goebel SU, Doppman JL, Gibril F 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; 17: 615-630.
56. Furukawa M, Raffeld M, Mateo C, Sakamoto A, Moody TW, Ito T et al. Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases. Clin Cancer Res 2005; 11: 3233-3242.
57. Chen YJ, Vortmeyer A, Zhuang Z, Gibril F, Jensen RT. X-chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth. Cancer 2004; 100: 1379-1387.
58. Chen YJ, Vortmeyer A, Zhuang Z, Huang S, Jensen RT. Loss of heterozygosity of chromosome 1q in gastrinomas: occurrence and prognostic significance. Cancer Res 2003; 63: 817-823.
59. Delcore R Jr, Cheung LY, Friesen SR. Characteristics of duodenal wall gastrinomas. Am J Surg 1990; 160: 621-623.
60. Ellison EC, Sparks J, Verducci JS, Johnson JA, Muscarella P, Bloomston M et al. 50-year appraisal of gastrinoma: recommendations for staging and treatment. J Am Coll Surg 2006; 202: 897-905.
61. Zogakis TG, Gibril F, Libutti SK, Norton JA, White DE, Jensen RT et al. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann Surg 2003; 238: 42-48.
62. Thodiyil PA, El-Masry NS, Williamson RC. Achieving eugastrinaemia in Zollinger-Ellison syndrome: resection or enucleation? Dig Surg 2001; 18: 118-123.
63. Stadil F, Bardram L, Gustafsen J, Efsen F. Surgical treatment of the Zollinger-Ellison syndrome. World J Surg 1993; 17: 463-467.
64. Bartsch DK, Fendrich V, Langer P, Celik I, Kann PH, Rothmund M. Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann Surg 2005; 242: 757-764.
65. Tonelli F, Fratini G, Nesi G, Tommasi MS, Batignani G, Falchetti A et al. Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias. Ann Surg 2006; 244: 61-70.
66. Melvin WS, Johnson JA, Sparks J, Innes JT, Ellison EC. Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia. Surgery 1993; 114: 1183-1188.
67. Norton JA, Fraker DL, Alexander HR, Gibril F, Liewehr DJ, Venzon DJ et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244: 410-419.
68. Proye C, Pattou F, Carnaille B, Paris JC, d'Herbomez M, Marchandise X. Intraoperative gastrin measurements during surgical management of patients with gastrinomas: experience with 20 cases. World J Surg 1998; 22: 643-649.
69. Thom AK, Norton JA, Axiotis CA, Jensen RT. Location, incidence, and malignant potential of duodenal gastrinomas. Surgery 1991; 110: 1086-1091.
70. Akerstrom G, Hessman O, Skogseid B. Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN1. Langenbecks Arch Surg 2002; 386: 558-569.
71. Norton JA, Jensen RT. Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome. Ann Surg 2004; 240: 757-773.
72. MacFarlane MP, Fraker DL, Alexander HR, Norton JA, Lubensky I, Jensen RT. Prospective study of surgical resection of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery 1995; 118: 973-979.
73. Fraker DL, Norton JA, Alexander HR, Venzon DJ, Jensen RT. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann Surg 1994; 220: 320-328.
74. Bartsch DK, Langer P, Wild A, Schilling T, Celik I, Rothmund M et al. Pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1: surgery or surveillance? Surgery 2000; 128: 958-966.
75. Norton JA, Alexander HR, Fraker DL, Venzon DJ, Gibril F, Jensen RT. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg 2001; 234: 495-505.
76. Thompson NW. Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both. J Intern Med 1998; 243: 495-500.
77. Pipeleers-Marichal M, Somers G, Willems G, Foulis A, Imrie C, Bishop AE et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 1990; 322: 723-727.
78. Imamura M, Komoto I, Doi R, Onodera H, Kobayashi H, Kawai Y. New pancreas-preserving total duodenectomy technique. World J Surg 2005; 29: 203-207.
79. Norton JA. Surgery and prognosis of duodenal gastrinoma as a duodenal neuroendocrine tumor. Best Pract Res Clin Gastroenterol 2005; 19: 699-704.
80. Touzios JG, Kiely JM, Pitt SC, Rilling WS, Quebbeman EJ, Wilson SD et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg 2005; 241: 776-785.
81. Que FG, Nagorny DM, Batts KP, Linz LJ, Kvols LK. Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg 1995; 169: 36-42.
82. Chen H, Hardacre JM, Uzar A, Cameron JL, Choti MA. Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? J Am Coll Surg 1998; 187: 88-92.
83. Chamberlain RS, Canes D, Brown KT, Saltz L, Jarnagin W, Fong Y et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 2000; 190: 432-445.
84. Nave H, Mossinger E, Feist H, Lang H, Raab H. Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years. Surgery 2001; 129: 170-175.
85. Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003; 197: 29-37.
86. Jaskowiak NT, Fraker DL, Alexander HR, Norton JA, Doppman JL, Jensen RT. Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome? Surgery 1996; 120: 1055-1062.
87. Fendrich V, Langer P, Celik I, Bartsch DK, Zielke A, Ramaswamy A et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors. Ann Surg 2006; 244: 845-853.
88. Norton JA, Doherty GM, Fraker DL, Alexander HR, Doppman JL, Venzon DJ et al. Surgical treatment of localized gastrinoma within the liver: a prospective study. Surgery 1998; 124: 1145-1152.
89. Metz DC, Pisegna JR, Fishbeyn VA, Benya RV, Jensen RT. Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. World J Surg 1993; 17: 468-480.
90. Corleto VD, Annibale B, Gibril F, Angeletti S, Serrano J, Venzon DJ et al. Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome? Aliment Pharmacol Ther 2001; 15: 1555-1561.
91. Ellison EC, Sparks J. Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing rumors? Am J Surg 2003; 186: 245-248.
92. Lew EA, Pisegna JR, Starr JA, Soffer EF, Forsmark C, Modlin IM et al. Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterology 2000; 118: 696-704.
93. Metz DC, Benya RV, Fishbeyn VA, Pisegna JR, Orbuch M, Strader DB et al. Prospective study of the need for long-term antisecretory therapy in patients with Zollinger-Ellison syndrome following successful curative gastrinoma resection. Aliment Pharmacol Ther 1993; 7: 247-257.
94. de Herder WW, Lamberts SW. Clinical endocrinology and metabolism. Gut endocrine tumours. Best Pract Res Clin Endocrinol Metab 2004; 18: 477-495.
95. Shojamanesh H, Gibril F, Louie A, Ojeaburu JV, Bashir S, Abou-Saif A et al. Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma. Cancer 2002; 94: 331-343.
96. Pisegna JR, Slimak GG, Doppman JL, Strader DB, Metz DC, Benya RV et al. An evaluation of human recombinant alpha interferon in patients with metastatic gastrinoma. Gastroenterology 1993; 105: 1179-1183.