The majority of carcinoid tumors are asymptomatic and found incidentally during endoscopy or surgery. When symptoms do occur, they vary depending on the site of disease. Symptoms from gastric carcinoids are more likely to occur in type III rather than type I or II tumors and can include abdominal pain, gastrointestinal bleeding, and weight loss [16]. Patients with disease of the small intestine can present with symptoms of obstruction or ischemia, including abdominal pain and intermittent diarrhea [17]. Appendiceal carcinoid tumors are most likely to present as acute appendicitis [18]. The large diameter of the colon frequently results in the absence of symptoms until the tumor has reached an advanced state. When present, the most common signs and symptoms include weight loss, diarrhea, abdominal tenderness, rectal bleeding, and a palpable abdominal mass [19]. Rectal carcinoids are frequently detected during screening of asymptomatic patients. Complaints attributable to these tumors include rectal bleeding, localized pain, change in bowel habits, and weight loss [20].

In patients clinically suspected of having a carcinoid tumor, laboratory studies can aid in the diagnosis. Serotonin produced by carcinoid tumors is metabolized in the liver and lung and converted to 5-hydroxyindoleacetic acid (5-HIAA). An elevation of 24-hour urine 5-HIAA levels has a specificity of approximately 88%, although the sensitivity is significantly lower [21]. Chromogranin A, which is secreted by many NE tumors, has greater sensitivity and is elevated in more than 80% of patients with carcinoid tumor [22]. A combination of elevated serum chromogranin A and 24-hour 5-HIAA levels seems to provide the best diagnostic approach. Other biochemical markers that have been studied include bradykinin, substance P, neurotensin, human chorionic gonadotropin, neuropeptide K, and neuropeptide PP; however, these are more complex to measure and not as accurate as chromogranin A and 5-HIAA [7]. In the case of gastric carcinoids, the additional measurement of gastrin levels assists in determining type [23].

Multiple imaging modalities are available for the evaluation of carcinoid tumors. CT scan is commonly used as an initial technique and has a sensitivity of approximately 80% [24]. Various protocols can increase the sensitivity, such as the use of intraluminal water, rapid intravenous contrast administration, multiplanar reconstructions, and, in the case of liver metastases, triple-phase contrast [25,26]. Single-photon emission CT (SPECT) and CT enteroclysis can also improve the accuracy of carcinoid tumor detection (Fig. 1) [26]. Features noted on CT scan include the presence of a polypoid intraluminal lesion, bowel wall thickening, and, in cases of mesenteric extension, a spiculated mesenteric mass [25]. MRI can be used as an alternative or adjunctive imaging modality; however, trials comparing MRI to CT have not demonstrated significant differences [24].

Fig. 1 SPECT/CT fusion study demonstrating carcinoid liver metastases.

(Courtesy of Dr Adrian Dawkins, Elizabeth Cheatham, Lexington, KT and Staci Allen, University of Kentucky, Lexington, KT.)

Somatostatin receptor scintigraphy can further characterize primary or metastatic disease. Somatostatin acts through membrane-bound receptors, 5 of which have been cloned and are designated somatostatin receptor types 1 through 5. Somatostatin receptor type 2 tends to be the most strongly expressed in neoplastic tissue [27]. Multiple analogs targeting these receptors are used in somatostatin receptor scintigraphy (eg, In-111 diethylenetriamine pentaacetic acid [DTPA]-octreotide, In-111 DTPA-lanreotide, and technetium Tc 99m depreotide). In-111 DTPA-octreotide, also known as OctreoScan, is the most commonly used agent for scintigraphy and has a reported sensitivity as high as 90% [24,28]. Indium In 111 DTPA-lanreotide has a lower sensitivity than its octreotide counterpart and is, therefore, generally not used for carcinoid tumors [29]. Technetium Tc 99m depreotide is approved specifically for lung cancer. It is less effective in the detection of abdominal carcinoid tumors due to the high level of background activity in the abdomen and the tracer’s short half-life [30].

Traditional fludeoxyglucose (FDG)-positron emission tomography (PET) is ineffective for carcinoid tumors due to their relatively slow rate of growth. PET has received increasing attention as a result of the introduction of multiple novel radionuclides, however, which may allow for more accurate imaging. Determining the effectiveness of these tracers has proved difficult due to the wide variety of available peptides, variations in production methods, and lack of adequately designed studies [30]. Radioactive carbon [¹¹C]5-HTP and ¹⁸F-DOPA are 2 recently introduced radioligands that are reported as more sensitive than somatostatin receptor scintigraphy. The instability of these products, however, necessitates their synthesis near the location where they are administered [28]. Radiogallium-labeled ligands also have promising characteristics, including their high affinity for somatostatin receptor types 2 and 5 and their rapid clearance from the circulatory system [31]. Two of these, [⁶⁸Ga-DOTA⁰, Tyr³]octreotide and [⁶⁸Ga-DOTA⁰,Tyr³]octreotate, have received particular attention due to their high affinity for somatostatin receptor subtype 2, their relative ease of production, and the existence of counterparts used in peptide receptor radionuclide therapy [28]. Overall, PET scanning can be considered for use in the diagnosis and staging of carcinoid disease; however, further studies are required to appropriately delineate the optimal technique and its exact role in clinical practice.

Endoscopy is a useful tool for the identification of gastric, duodenal, colonic, and rectal carcinoid tumors as well as for obtaining biopsies for histologic diagnosis. The addition of endoscopic ultrasound also allows for determination of the depth of invasion and local lymph node involvement in these tumor types, thus enabling more accurate staging. Capsule endoscopy may play a role in the surveillance of small bowel carcinoids, but the ability to localize the lesion is limited.

Barium studies are sometimes performed during the work-up of symptoms related to carcinoid disease, such as diarrhea or abdominal pain. The radiologic appearance of small bowel carcinoids in these studies is nonspecific. Features include submucosal nodules, barium-filled craters known as target lesions resulting from mucosal ulceration, and thickening of the bowel wall from tumor infiltration and ischemia [25]. The use of angiography and high-resolution ultrasound has been described; however, these techniques are not routinely performed due to the frequency of nonspecific findings [8]. Metaiodobenzylguanidine imaging has also been studied, but this method is less accurate than OctreoScan and generally not indicated in the diagnosis of carcinoids [32].

The treatment of gastric carcinoid tumors is based on type (summarized in Table 1). Because of the excellent prognosis associated with types I and II gastric carcinoids, these tumors have increasingly been treated with more conservative measures. Regular endoscopic surveillance or endoscopic resection, which consists of polypectomy or endoscopic mucosal resection, is appropriate for tumors less than 1.0 cm in size [9,23]. Surgical resection should be considered if a tumor is greater than 1 cm or increasing in size, if there is concern for gastric adenocarcinoma on biopsy, or if a patient is unable to undergo endoscopic surveillance [23]. Surgery may consist of partial or total gastrectomy depending on the extent of tumor involvement [16]. In type I gastric carcinoids, antrectomy is an additional treatment option, particularly when multiple tumors make complete resection difficult [16]. Antrectomy removes the majority of G cells of the stomach, thus resulting in the reversal of enterochromaffin-like hyperplasia. This technique is effective in more than 80% of cases [33]. Type III gastric carcinoids are considerably more aggressive and should be treated with radical gastric resection and lymph node removal [16].

Table 1 Surgical treatment of gastrointestinal carcinoid tumors

Abbreviations: APR, abdominoperineal resection; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; LAR, low anterior resection; RFA, radio frequency ablation.

Duodenal carcinoid tumors are rare, which makes a standardized treatment protocol difficult to develop. Tumors less than 1 cm can generally be treated with endoscopic resection [34]. For tumors between 1 cm and 2 cm, achieving complete endoscopic resection may be more difficult; therefore, an open, transduodenal excision is often a more appropriate approach [34]. In a recent study, lymph node metastases were detected even in tumors less than 1 cm that were confined to the submucosa [35]