Surgical Management of Neuroendocrine Tumors of the Gastrointestinal Tract

Neuroendocrine tumors of the pancreas (islet cell tumors) and of the luminal gastrointestinal tract (carcinoids) are a heterogeneous group of epithelial neoplasms that share certain common characteristics. First, they are similar histologically and are difficult to distinguish under light microscopy. Second, they can be associated with hypersecretory syndromes. Third, they are generally slow-growing and have a better prognosis than adenocarcinomas at the same site; however, they do become incurable when they progress to unresectable metastatic disease. Surgery is the only curative treatment and is recommended for most patients for whom cross-sectional imaging suggests that complete resection is possible. This article reviews the surgical management of gastrointestinal neuroendocrine tumors, including the preoperative control of hormonal symptoms, extent of resection required, postoperative outcomes, and differing management strategies as determined by whether the tumor has arisen sporadically or as part of a familial disorder, such as multiple endocrine neoplasia type 1 (MEN1).

Neuroendocrine tumors (NETs) are a diverse group of epithelial tumors that can originate from almost any organ derived from the primitive endoderm, including pancreatic islet cells (pancreatic NETs), diffuse neuroendocrine cells distributed throughout the gut (gastrointestinal carcinoids), the respiratory epithelium (bronchial carcinoids), the thymus (thymic carcinoids), and parafollicular cells distributed within the thyroid gland (medullary thyroid carcinoma). Despite their different sites of origin, however, these tumors can be considered as a common entity since they are very difficult to distinguish under the microscope and can share certain common biological features, such as an association with hormonal hypersecretory syndromes. The purpose of this article is to review the important aspects of the diagnosis, preoperative treatment, and operative treatment of neuroendocrine tumors of the pancreas and the luminal gastrointestinal tract. Specific management strategies, which are dependent on whether the tumor has arisen sporadically or as part of a familial disorder, such as multiple endocrine neoplasia type 1 (MEN1), are also discussed.

Pancreatic Neuroendocrine Tumors

Pancreatic NETs (PNETs) account for 2% of all pancreatic neoplasms.[1] Their annual incidence in the United States is estimated to be approximately three cases per million persons but appears to be increasing.[2] The majority of these tumors can be associated with the hypersecretion of detectable hormones, such as insulin, gastrin, glucagon, vasoactive intestinal polypeptide (VIP), or somatostatin, leading to specific clinical syndromes. PNETs generally arise sporadically. However, 80% to 100% of patients with MEN1 will develop a PNET, most commonly a gastrinoma, with insulinoma the next most common type.[3]

Insulinoma

Insulinoma is the most common functional sporadic PNET. Clinical symptoms result from episodes of hypoglycemia; patients can present with neuroglycopenia (headaches, blurred vision, confusion) or sympathoadrenal stimulation (tachycardia, diaphoresis).[4] Symptoms can be insidious and are often prevented or ameliorated by increased caloric intake, sometimes leading to weight gain. Although Dr. Alan Whipple's diagnostic triad of symptomatic hypoglycemia, low blood glucose level, and relief of symptoms with glucose administration is still valid,[5] most patients today are diagnosed using a monitored fast and serial serum measurements of glucose and insulin every 4 to 6 hours. The fast is terminated after 72 hours-or sooner if the patient develops neuroglycopenic symptoms.[4] Measurement of serum proinsulin and C-peptide levels is useful in ruling out surreptitious insulin administration (the condition is ruled out if these values are elevated).

The first step in the management of insulinomas consists of dietary changes and medical control of the symptoms. Adding cornstarch to the diet can slow the absorption of food, while diazoxide (Proglycem), an antihypertensive, can suppress insulin secretion in approximately 60% of patients.[6] For patients unable to tolerate the nausea, hirsutism, and sodium retention associated with diazoxide, other options include calcium channel blockers, beta-adrenergic antagonists, and octreotide (Sandostatin).

FIGURE 1

Pancreatic Insulinoma

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