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PANCREATIC & DUODENAL NEUROENDOCRINE TUMORS* ISLET CELL TUMORS
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Half the tumors are nonsecretory; weight loss, abdominal pain, or jaundice may be presenting signs Secretory tumors cause a variety of manifestations depending on the hormones secreted
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The pancreatic islets are composed of several types of cells, each with distinct chemical and microscopic features: the A cells (20%) secrete glucagon, the B cells (70%) secrete insulin, and the D cells (5%) secrete somatostatin or gastrin F cells secrete pancreatic polypeptide Each type of cell may give rise to benign or malignant neoplasms that may be
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*Diabetes mellitus and hyperglycemia are discussed in 27
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multiple and usually present with a clinical syndrome related to hypersecretion of a native or ectopic hormonal product The endocrine diagnosis of a particular pancreatic islet neoplasm depends on first suspecting it from its clinical manifestations Many tumors secrete two or more different hormones Insulinomas are usually (about 82%) benign and secrete excessive amounts of insulin (as well as proinsulin and Cpeptide), which causes hypoglycemia The tumors may be multiple, especially in familial MEN 1 about 12% of cases (see 27) Gastrinomas secrete excessive quantities of the hormone gastrin (as well as big gastrin), which stimulates the stomach to hypersecrete acid, thereby causing hyperplastic gastric rugae and peptic ulceration (Zollinger Ellison syndrome) Most gastrinomas are benign, but some are malignant and metastasize to the liver Gastrinomas are typically found in the duodenum (49%), pancreas (24%), or lymph nodes (11%) Presenting symptoms and signs include abdominal pain (75%), diarrhea (73%), heartburn (44%), bleeding (25%), or weight loss (17%) Endoscopy usually discovers prominent gastric folds (94%) Sporadic Zollinger Ellison syndrome is rarely suspected at the onset of symptoms; typically, there is a 5-year delay in diagnosis About 22% of patients have MEN 1 MEN 1 usually presents in patients who are younger; hyperparathyroidism may occur from 14 years preceding the Zollinger Ellison diagnosis to 38 years afterward (See Multiple Endocrine Neoplasia, below) Therapy with high doses of proton pump inhibitors (quadruple usual doses) is usually effective Surgery is not usually performed because of the low cure rates, particularly in patients with MEN 1 Note that serum gastrin levels tend to be high in any patient who is taking a proton pump inhibitor; hypercalcemia also stimulates gastrin release The 5-, 10-, and 20-year survival rates with MEN 1 are 94%, 75%, and 58%, respectively, while the survival rates for sporadic Zollinger Ellison syndrome are 62%, 50%, and 31%, respectively (See 14) Glucagonomas are usually malignant; weight loss and liver metastases are ordinarily present by the time of diagnosis They usually secrete other hormones besides glucagon, often gastrin Other initial symptoms often include diarrhea, nausea, peptic ulcer, or necrolytic migratory erythema About 35% of patients ultimately develop diabetes The median survival is 28 years after diagnosis Somatostatinomas are very rare and are associated with weight loss, diabetes mellitus, malabsorption, and hypochlorhydria Other rare tumors secrete excessive amounts of vasoactive intestinal polypeptide (VIP), a substance that causes profuse watery diarrhea (Verner Morrison syndrome) Treatment with octreotide improves the symptoms but does not halt tumor growth Symptomatic improvement with calcitonin treatment has also been reported Islet cell tumors can secrete ectopic hormones in addition to native hormones, often in combinations producing a variety of clinical syndromes They may secrete ACTH, producing Cushing s syndrome Secretion of serotonin can produce an atypical carcinoid syndrome manifested by pain, diarrhea, and weight loss; skin flushing occurs in only 39% of patients
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Pancreatic carcinoid tumors grow slowly but usually metastasize to local and distant sites, particularly to other endocrine organs Islet cell tumors may be part of the syndrome of multiple endocrine adenomatosis type I (with pituitary and parathyroid adenomas) Localization of noninsulinoma pancreatic islet cell tumors and their metastases is best done with somatostatin receptor scintigraphy (SRS); SRS detects about 75% of noninsulinomas CT and MRI are also useful Insulinomas can usually be located preoperatively by endoscopic ultrasonography For insulinomas, preoperative localization studies are less successful and have the following sensitivities: ultrasonography 25%, CT 25%, endoscopic ultrasonography 27%, transhepatic portal vein sampling 40%, arteriography 45%, intraoperative palpation 55%, and intraoperative pancreatic ultrasound 75% Nearly all insulinomas can be successfully located at surgery by intraoperative palpation and ultrasound An abdominal CT scan is usually obtained, but extensive preoperative localization procedures, especially with invasive methods, are not required Tumors may be located in the pancreatic head or neck (57%), body (15%), or tail (19%) or in the duodenum (9%) Direct resection of the tumor (or tumors), which often spreads locally, is the primary form of therapy for all types of islet cell neoplasm except Zollinger Ellison syndrome, where use of high doses of a proton pump inhibitor is the therapy of choice Insulinomas are resected However, in MEN 1, insulinomas are rarely cured, so surgery is reserved for dominant masses in such cases Palliation of functioning malignant disease often requires both antihormonal and anticancer chemotherapy The use of streptozocin, doxorubicin, and asparaginase, especially for malignant insulinoma, has produced some encouraging results, though these drugs are quite toxic The hypoglycemia of insulinoma may be counteracted by verapamil or diazoxide Octreotide LAR is useful in the therapy of islet cell tumors with the exception of insulinoma; monthly subcutaneous injections of 20 30 mg are required The prognosis in these neoplasms is variable The surgical complication rate is about 40%, with patients commonly developing fistulas and infections Extensive pancreatic resection may cause diabetes mellitus The overall 5-year survival is higher with functional tumors (77%) than with nonfunctional ones (55%) and higher with benign tumors (91%) than with malignant ones (55%)
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Finlayson E et al Surgical treatment of insulinomas Surg Clin North Am 2004 Jun;84(3):775 85 [PMID: 15145234] Hirshberg B et al Malignant insulinoma: spectrum of unusual clinical features Cancer 2005 Jul 15;104(2):264 72 [PMID: 15937909] Norton JA et al Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome Ann Surg 2004 Nov;240(5):757 73 [PMID: 15492556] Warner RR Enteroendocrine tumors other than carcinoid: a review of clinically significant advances Gastroenterology 2005 May;128(6):1668 84 [PMID: 15887158]
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