Table of Contents Purpose of This PDQ Summary General Information Cellular Classification Stage Information
Gastrinoma Insulinoma Glucagonoma Miscellaneous Islet Cell Tumors Recurrent Islet Cell Tumors Get More Information From NCI Changes to This Summary (10/31/2008) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of islet cell tumors (endocrine pancreas). This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Diagnostic information.
- Cellular classification.
- Staging.
- Treatment options for different types of tumors.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
Back to Top General Information
Cancer of the endocrine pancreas includes a highly treatable and often curable
collection of tumors. They are uncommon cancers with 200 to 1,000 new cases
per year and occur in only 1.5% of detailed autopsy series. Islet tumors may
either be functional (produce one or more hormones) or nonfunctional. The
majority of functioning tumors that produce insulin are benign; however, 90% of
nonfunctioning tumors are malignant. Many islet cell cancers are
nonfunctional and produce symptoms from tumor bulk or metastatic dissemination.
Because of the presence of several cell types in the pancreatic islet cells
(alpha, beta, delta, A, B, C, D, E), the term islet cell tumors refers to at
least five distinct cancers, which when functional, produce unique metabolic
and clinical characteristics. Since the clinical manifestations in functional
tumors may result from the metabolic effects of polypeptide(s) secreted by the
cancer cells rather than from tumor bulk or metastatic disease, each tumor type
must be considered separately, both diagnostically and therapeutically.[1-3]
Functional tumors may be too small in size to be detected by conventional
imaging techniques.
The frequent long delays between initial symptoms and diagnosis and the varied
effects of the polypeptides secreted often necessitate involvement of multiple
surgical and medical subspecialties. Surgery is the only curative
modality.[4,5] Even in those cases not resectable for cure, effective
palliation may be achieved because of the slow-growing nature of the majority
of these tumors and the potential use of antihormonal pharmacologic therapy
(for example, cimetidine in the ulcer-producing Zollinger-Ellison syndrome).
Combination chemotherapy may provide effective palliation as well as increased
survival in selected patients. In patients with indolent, slow-growing
metastatic islet cell tumors, the best therapy may be careful observation
and no treatment until palliation is required. Patients with multiple
endocrine neoplasia syndrome type 1, an autosomal dominant condition in which
85% have pancreatic islet cell tumors, 90% have hyperparathyroidism, and 65%
have pituitary tumors, are less likely to be cured by pancreatic resection than
are patients with sporadic islet cell tumors. With the exception of pain
relief from bone metastases, radiation therapy has a limited role in this
disease.
References
-
Kent RB 3rd, van Heerden JA, Weiland LH: Nonfunctioning islet cell tumors. Ann Surg 193 (2): 185-90, 1981.
[PUBMED Abstract]
-
Modlin IM, Lewis JJ, Ahlman H, et al.: Management of unresectable malignant endocrine tumors of the pancreas. Surg Gynecol Obstet 176 (5): 507-18, 1993.
[PUBMED Abstract]
-
Delcore R, Friesen SR: Gastrointestinal neuroendocrine tumors. J Am Coll Surg 178 (2): 187-211, 1994.
[PUBMED Abstract]
-
Danforth DN Jr, Gorden P, Brennan MF: Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery. Surgery 96 (6): 1027-37, 1984.
[PUBMED Abstract]
-
Evans DB, Skibber JM, Lee JE, et al.: Nonfunctioning islet cell carcinoma of the pancreas. Surgery 114 (6): 1175-81; discussion 1181-2, 1993.
[PUBMED Abstract]
Back to Top Cellular Classification
Endocrine Tumors of the Pancreas
Islet cells
|
Secreted active agent
|
Tumor and syndrome
|
Alpha |
Glucagon |
Glucagonoma (diabetes,
dermatitis) |
Beta |
Insulin |
Insulinoma (hypoglycemia) |
Delta |
Somatostatin |
Somatostatinoma (mild diabetes) |
D |
Gastrin |
Gastrinoma (peptic ulcer disease) |
A -> D |
Vasoactive Intestinal Peptide (VIP) and/or other undefined mediators |
WDHA (watery diarrhea, hypokalemia, achlorhydria) |
serotonin (5-HT) |
Carcinoid |
ACTH |
Cushing disease |
MSH |
Hyperpigmentation |
Interacinar cells
|
Secreted active agent
|
Tumor and syndrome
|
F |
Pancreatic polypeptide |
Multiple hormonal syndromes |
EC |
5-HT |
Carcinoid |
Back to Top Stage Information
There is no detailed or generally accepted staging system for islet cell
cancer; however, a logical division of these tumors follows:
- Islet cell cancers occurring in one site.
- Islet cell cancers occurring in several sites.
- Islet cell cancers metastatic to regional lymph nodes or distant sites.
Gastrinoma
Diagnosis is dependent on elevated serum gastrin and elevated gastric acid
levels. Provocative testing with calcium and secretin shows considerable
overlap, and the value of these tests is limited. Zollinger-Ellison syndrome
(ZES) is a syndrome of unrelenting peptic ulcer disease, diarrhea, and gastric
hyperacidity, associated with a gastrin-producing tumor. (For more information on diarrhea, refer to the Gastrointestinal Complications summary.) It accounts for less
than 1% of all peptic ulcer disease. Sixty percent to 75% of gastrinomas associated with
multiple endocrine neoplasia syndrome type 1 (MEN-1) are malignant with
metastasis at diagnosis. Sporadic gastrinomas are less often malignant; 70%
are multicentric.
Diagnostic tests:
- BAO:MAO ≥ = 0.6 (Basal Acid Output:Maximal Acid Output).
- Overnight AO ≥ = 100 mmols.
- BAO ≥ = 10 mmols/hr.
- Serum gastrin 10 times normal, or greater than 500 pg/mL (Note: the
accuracy of gastrin assays may vary widely).
- Secretin test: 1 unit/kg IV rapid injection: Positive = 100% increase
in gastrin within 10 minutes; 2 units/kg: Positive = 100% increase
over baseline.
- Elevated human chorionic gonadotropin levels.
In the era of proton pump inhibitors and H2 blocking agents, the potentially
lethal hyperacidity and hypersecretory states induced by excessive gastrin
production can be controlled. In a series of 212 patients with ZES, no
patients died of causes related to acid hypersecretion despite the fact that
only 2.3% of patients had been subjected to total gastrectomy and that the
cohort upon which the report was based had a long median follow-up period of
13.8 years. Although 32% of the patients died during the course of the study, only 50%
of the 67 deaths were attributable to ZES-related causes that were mainly liver
metastases with progressive anorexia and cachexia (67%) or secondary endocrine
tumors consequent to MEN-1 syndrome. The
development of bone or liver metastases (especially diffuse liver disease) or
of ectopic Cushing syndrome during the study period predicted for
significantly decreased survival times.[1]
Insulinoma
Insulinomas are far more likely to be benign than malignant. Only 10% are
multiple and only 10% are malignant; 10% are associated with MEN-1. The
clinical manifestations are those of hypoglycemia, which is produced by
inappropriate secretion of insulin by the tumor. These tumors may occur alone
or as part of a MEN syndrome. Fasting hypoglycemia (<40 mg/dL) associated with
an elevated insulin level (in the absence of exogenous administration of
insulin) is pathognomonic. Measurement of plasma proinsulin may be helpful for
diagnosing insulin-secreting carcinoma. These are usually slow-growing tumors
and, when localized to the pancreas or regional lymph nodes, can be cured with
pancreatic resection. The approach to management depends on carefully
performed preoperative localization studies and the findings at exploratory
laparotomy.[2-4] One large retrospective series has suggested that
extensive preoperative radiologic studies are neither clinically effective nor
cost effective because intraoperative ultrasound and visual inspection of the
pancreas at surgery localize most occult insulinomas.[5]
Glucagonoma
Glucagonoma is the third most common endocrine-secreting islet cell tumor, and 70% of glucagonomas are malignant. Necrolytic migratory erythema, hyperglycemia,
and venous thrombosis comprise a virtually diagnostic triad. The measurement of serum glucagon confirms the diagnosis.
Miscellaneous
The following classifications are considered under miscellaneous:
- VIPoma (Verner-Morrison Syndrome) - characterized by watery diarrhea,
hypokalemia, achlorhydria (WDHA).
- Somatostatinoma - 90% malignant, adult onset diabetes.
- Pancreatic polypeptide.
These are rare but defined clinical syndromes associated with specific
polypeptide hormone production by islet cell tumors. Because of their rarity
and similar approaches to management, they are grouped in this section.
References
-
Yu F, Venzon DJ, Serrano 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 17 (2): 615-30, 1999.
[PUBMED Abstract]
-
Danforth DN Jr, Gorden P, Brennan MF: Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery. Surgery 96 (6): 1027-37, 1984.
[PUBMED Abstract]
-
Kahn CR, Rosen SW, Weintraub BD, et al.: Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors. A specific marker for malignancy. N Engl J Med 297 (11): 565-9, 1977.
[PUBMED Abstract]
-
Pasieka JL, McLeod MK, Thompson NW, et al.: Surgical approach to insulinomas. Assessing the need for preoperative localization. Arch Surg 127 (4): 442-7, 1992.
[PUBMED Abstract]
-
van Heerden JA, Grant CS, Czako PF, et al.: Occult functioning insulinomas: which localizing studies are indicated? Surgery 112 (6): 1010-4; discussion 1014-5, 1992.
[PUBMED Abstract]
Back to Top Gastrinoma
The approach to treatment often depends on the results of preoperative
localization studies and findings at exploratory laparotomy. At exploration,
85% of these tumors are found in the gastrinoma triangle with 40% on the
surface of the pancreas and 40% outside of the pancreas. Only 15% are found
within the substance of the pancreas. Percutaneous transhepatic venous
sampling may occasionally provide accurate localization of single sporadic
gastrinomas. Total gastrectomy is no longer considered the immediate treatment
of choice and is selectively used depending on effectiveness of other
treatment programs.[1]
Standard treatment options:
- Single lesion in head of the pancreas:
- Enucleation.
- Parietal cell vagotomy and cimetidine.
- Total gastrectomy (in very unusual circumstances).
- Single or multiple lesions in the duodenum:
- Single lesion in body/tail of the pancreas:
- Multiple lesions in pancreas:
- Resection of body/tail and, if residual disease is present,
- Parietal cell vagotomy and cimetidine, or
- Total gastrectomy.
- No tumor found:
- Parietal cell vagotomy and cimetidine.
- Total gastrectomy.
- Liver metastases:
- Liver resection where possible; radiofrequency ablation and cryosurgical ablation are options.
- Chemoembolization of liver.
- Metastatic disease or disease refractory to surgery and cimetidine:
- Combination chemotherapy: doxorubicin plus streptozocin or fluorouracil plus
streptozocin in patients when doxorubicin is contraindicated.[2]
- Somatostatin analogue therapy (SMS 201-995).[3]
Patients with hepatic-dominant disease and substantial symptoms caused by tumor
bulk or hormone-release syndromes may benefit from procedures that reduce
hepatic arterial blood flow to metastases (hepatic arterial occlusion with
embolization or with chemoembolization). Such treatment may also be combined
with systemic chemotherapy in selected patients.[4] Treatment with proton pump inhibitors or H2 blocking agents may aid in control of peptic symptoms.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with gastrinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Glowniak JV, Shapiro B, Vinik AI, et al.: Percutaneous transhepatic venous sampling of gastrin: value in sporadic and familial islet-cell tumors and G-cell hyperfunction. N Engl J Med 307 (5): 293-7, 1982.
[PUBMED Abstract]
-
Moertel CG, Lefkopoulo M, Lipsitz S, et al.: Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326 (8): 519-23, 1992.
[PUBMED Abstract]
-
Kvols LK, Buck M, Moertel CG, et al.: Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med 107 (2): 162-8, 1987.
[PUBMED Abstract]
-
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
[PUBMED Abstract]
Back to Top Insulinoma
Standard treatment options:
- Single lesion in head of pancreas or single lesion less than 1.0 cm in tail
of pancreas:
- Enucleation, if feasible.
- Single lesion in body/tail greater than 1.0 cm:
- Multiple lesions: occur in 10%, suspect multiple endocrine neoplasia syndrome type 1 (MEN-1):
- Metastatic lesions-lymph nodes or distant sites:
- Resect when possible. Consider radiofrequency or cryosurgical ablation if not resectable.
- Unresectable:
- Combination chemotherapy: doxorubicin plus streptozocin or fluorouracil plus
streptozocin in patients when doxorubicin is contraindicated.[1,2]
- Pharmacologic palliation: diazoxide 300 to 500 mg/day
- Somatostatin analogue therapy (SMS 201-995).[3] Necrotizing erythema of glucagonoma is relieved in 24 hours with somatostatin analogue, with nearly complete disappearance within 1 week.
Patients with hepatic-dominant disease and substantial symptoms caused by tumor
bulk or hormone-release syndromes may benefit from procedures that reduce
hepatic arterial blood flow to metastases (hepatic arterial occlusion with
embolization or with chemoembolization). Such treatment may also be combined
with systemic chemotherapy in selected patients.[4]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with insulinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Danforth DN Jr, Gorden P, Brennan MF: Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery. Surgery 96 (6): 1027-37, 1984.
[PUBMED Abstract]
-
Moertel CG, Lefkopoulo M, Lipsitz S, et al.: Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326 (8): 519-23, 1992.
[PUBMED Abstract]
-
Kvols LK, Buck M, Moertel CG, et al.: Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med 107 (2): 162-8, 1987.
[PUBMED Abstract]
-
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
[PUBMED Abstract]
Back to Top Glucagonoma
Standard treatment options:
- Single lesion in head of pancreas or single lesion less than 1.0 cm in tail
of pancreas:
- Enucleation, if feasible.
- Single lesion in body/tail greater than 1.0 cm:
- Multiple lesions:
- Metastatic disease-lymph nodes or distant sites:
- Resect when possible. Consider radiofrequency or cryosurgical ablation if not resectable.
- Unresectable disease:
- Combination chemotherapy: doxorubicin plus streptozocin or fluorouracil
plus streptozocin in patients for whom doxorubicin is contraindicated.[1]
- Somatostatin analogue therapy (SMS 201-995).[2]
Necrotizing erythema of glucagonoma is relieved in 24 hours with somatostatin analogue, with nearly complete disappearance within 1 week.
Patients with hepatic-dominant disease and substantial symptoms caused by tumor
bulk or hormone-release syndromes may benefit from procedures that reduce
hepatic arterial blood flow to metastases (hepatic arterial occlusion with
embolization or with chemoembolization). Such treatment may also be combined
with systemic chemotherapy in selected patients.[3]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with glucagonoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Moertel CG, Lefkopoulo M, Lipsitz S, et al.: Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326 (8): 519-23, 1992.
[PUBMED Abstract]
-
Kvols LK, Buck M, Moertel CG, et al.: Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med 107 (2): 162-8, 1987.
[PUBMED Abstract]
-
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
[PUBMED Abstract]
Back to Top Miscellaneous Islet Cell Tumors
Standard treatment options:
For watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome,
somatostatinoma, and pancreatic polypeptide:
- Single lesion in head of pancreas or single lesion less than 1.0 cm in tail
of pancreas:
- Enucleation, if feasible.
- Single lesion in body/tail greater than 1.0 cm:
- Multiple lesions:
- Metastatic disease-lymph nodes or distant sites:
- Resect when possible. Consider radiofrequency or cryosurgical ablation if not resectable.
- Unresectable disease:
- Combination chemotherapy: doxorubicin plus streptozocin or fluorouracil
plus streptozocin in patients for whom doxorubicin is contraindicated.[1]
- Somatostatin analogue therapy (SMS 201-995) for WDHA syndrome
and pancreatic polypeptide.[2]
Necrotizing erythema of glucagonoma is relieved in 24 hours with somatostatin analogue, with nearly complete disappearance within 1 week.
Patients with hepatic-dominant disease and substantial symptoms caused by tumor
bulk or hormone-release syndromes may benefit from procedures that reduce
hepatic arterial blood flow to metastases (hepatic arterial occlusion with
embolization or with chemoembolization). Such treatment may also be combined
with systemic chemotherapy in selected patients.[3]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with islet cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Moertel CG, Lefkopoulo M, Lipsitz S, et al.: Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326 (8): 519-23, 1992.
[PUBMED Abstract]
-
Kvols LK, Buck M, Moertel CG, et al.: Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). Ann Intern Med 107 (2): 162-8, 1987.
[PUBMED Abstract]
-
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
[PUBMED Abstract]
Back to Top Recurrent Islet Cell Tumors
Deciding on further treatment depends on many factors, including the specific
cancer, prior treatment, and site of recurrence, as well as individual patient
considerations. Clinical trials are appropriate and should be considered when
possible. Attempts at
re-resection are worthwhile for patients with gastrinomas, insulinomas, and
glucagonomas. Somatostatin analogues will aid in control of syndromes of some
of these tumors. Intra-arterial chemotherapy has been useful for a number of
patients with liver metastases. Patients with hepatic-dominant disease and
substantial symptoms caused by tumor bulk or hormone-release syndromes may
benefit from continuous-infusion intra-arterial chemotherapy or procedures that
reduce hepatic arterial blood flow to metastases (hepatic arterial occlusion
with embolization or with chemoembolization). Such treatment may also be
combined with systemic chemotherapy in selected patients.[1]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent islet cell carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
-
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
[PUBMED Abstract]
Back to Top Get More Information From NCI
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Back to Top Changes to This Summary (10/31/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
Back to Top More Information
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