Carcinoid tumors generally are classified based on the location in the primitive gut (ie, foregut, midgut, hindgut) that gives rise to the tumor. Foregut carcinoid tumors are divided into sporadic primary tumors and tumors secondary to achlorhydria. The term sporadic primary foregut tumor encompasses carcinoids of the bronchus, stomach, proximal duodenum, and pancreas. Midgut tumors are derived from the second portion of the duodenum, the jejunum, the ileum, and the right colon. These account for 60-80% of all carcinoid tumors (especially those of the appendix and distal ileum) in adults and are also seen in children
Diagnosis and Treatment:
A number of imaging modalities have been used to detect carcinoid tumors. These modalities include plain radiography, upper- and lower-GI radiography with the use of oral contrast agents, CT, MRI, angiography, positron emission tomography (PET), scintigraphy with metaiodobenzylguanidine (MIBG) and octreotide (Monsieurs, 2001; Shi, 1998), radionuclide imaging with somatostatin analogs attached to the radioactive tracer, and technetium-99m bone scanning. Depending on the location of the tumor and metastasis, a combination of these may be used.
GI series, CT, and MRI may be helpful in some situations.
For the diagnosis of chest tumors, CT combined with scintigraphy with octreotide is preferred.
In the large bowel, the disease is often detected with colonoscopy and does not provide an imaging challenge. Imaging diagnosis of small-bowel carcinoids is relatively difficult. Small tumors in this location are difficult to detect on upper-GI series and CT scans, and other techniques are required.
Mesenteric invasion and liver metastasis are often detected on CT scans. MRI can also be helpful in the diagnosis of hepatic disease but is less sensitive than CT in detection of extrahepatic lesions.
With advances in imaging studies, angiography is rarely used and is reserved for equivocal situations.
PET scanning can be helpful and is increasingly used for diagnosis and follow-up of the tumors.
Scintigraphy with MIBG and octreotide scanning have been used to successfully detect carcinoid tumors (Kaltsas, 2001). Octreotide scanning appears to be more sensitive than MIBG imaging.
Radionuclide imaging with somatostatin analogs attached to radioactive tracer can be used to advantage for diagnosis of carcinoid tumors.
Radiotracers currently used include indium-111 diethylenetriamine pentaacetic acid (111 In-DTPA) and yttrium. Most neuroendocrine tumors have receptors for somatostatins. Five somatostatin receptor subtypes, designated SSTR-1 to SSTR-5, are identified. Binding affinity of somatostatin analogs to these subtypes may vary, with highest affinity for SSTR-2, medium affinity for SSTR-2 and SSTR-5, and lowest affinity for SSTR-1 and SSTR-4. Carcinoid tumors often express SSTR-1 to SSTR-3 and, infrequently, SSTR-2. Nevertheless, for tumors that measure less than 1 cm in diameter, the sensitivity of111 In-DTPA octreotide imaging reaches 80-90%.
This technique can be used to identify primary and metastatic disease and is approved for radionuclide scanning of carcinoid tumors. An advantage is that, if the result is positive, this technique can be used as a treatment modality.
In a study of 40 patients, somatostatin-receptor scintigraphy (SRS) helped in detecting localized tumors in 78% of patients versus 82% with CT scanning. However, SRS helped in identifying primary tumors in 2 patients missed on CT scanning. In 16% of patients, SRS depicted lesions not found with other modalities. No false-positive results were observed.
Overall, SRS appears to be the imaging method of choice for localizing and evaluating the extent of carcinoid tumor.
Bone metastasis is not uncommon in carcinoid tumors. In a study of 12 patients, 11 of whom had liver metastasis, 8 had bone involvement, as detected on SRS.
Technetium-99m bone scanning can aid in the detection of metastases.
Endoscopy, including bronchoscopy, esophagogastroscopy, gastroscopy, and colonoscopy, can be used for biopsy and diagnosis.
If metastases occur and surgical excision is not suitable, consider treatment with currently recommended chemotherapy.
Chemotherapeutic agents currently used in clinical trials to palliate metastatic carcinoid disease include the following:
Somatostatin analogs with a radioactive load
A combination of the agents listed above is typically used.
In one study, 8 adults with carcinoid tumor metastatic to liver were treated with intra-arterial 5-fluorouracil and embolization of hepatic tumors with bovine collagen fiber admixed with iohexol, cisplatin, mitomycin C, and doxorubicin. This treatment resulted in symptomatic relief and tumor regression in 4 patients and stabilized the disease in the rest of the patients.
Octreotide, a somatostatin analog, is highly effective in reducing symptoms; however, in the pediatric age group, stunted linear growth is of concern.
Octreotide reduces the amount of the growth factor produced and, thus, theoretically impairs growth.
Intermittent and continuous infusions of octreotide have been reported, with superior results obtained with the latter.
Such treatment can result in near-normalization of the plasma insulinlike growth factor I and partial suppression of plasma growth hormone–releasing hormone (GHRH) (Lefebvre, 1995).
The availability of a long-acting somatostatin analog that can be given once a month has eliminated the need for injections 2-3 times per day, with equal efficacy (Rubin, 1999).
In metastatic carcinoid tumors, long-term use of octreotide is reported. However, receptor alteration induced during the use of this agent requires consecutive drug dosage increase to control the symptoms (Corleto, 2000).
At present, no formal, well-designed study has been performed to systematically measure the effects of this modality of therapy. Although experience is limited, adverse effects in children have been similar to those in adults. Adverse effects include gallstones and steatorrhea, which may sometimes require pancreatic enzyme replacement. Local irritation at the injection site is a common complaint. These adverse effects must be weighted against the potential benefits.
In situ targeted therapy with somatostatin analogs (eg, octreotide attached to a radioactive load using yttrium-90 or111 Indium-labeling agents) provides promise for patients with unresectable tumors. This therapy is currently used on an experimental basis in adults and children.
The treatment of choice is surgical excision, if feasible. The surgical technique may vary according to the type or location of the tumor.
In most appendiceal tumors, simple appendectomy is sufficient for treatment. In intestinal carcinoids, block resection of the tumor with adjacent lymph nodes must be attempted. In the bronchial location, aggressive surgical resection, and not bronchoscopic removal, is recommended (Fink, 2001; Fauroux, 2005).
In localized tumors, surgical resection can result in cure, with 70-90% survival rate.
When total resection is not possible, debulking may provide symptomatic relief.
For hepatic tumors, surgical ligation of the hepatic artery can potentially deprive blood supply to the tumor cells and cause necrosis while preserving most of the normal live cells. However, new blood vessels develop over time and restore circulation.
Intra-arterial infusion of chemotherapeutic agents with chemoembolization of the hepatic artery may also provide effective, albeit short term, relief of symptoms due to hepatic metastasis in cases of carcinoid tumors.
If hepatic metastasis is present but resectable, surgical resection is preferred
HCG Cancer centre