General diagnostic approaches
As might be expected, diagnostic approaches to GI carcinoids vary according to anatomical location. In 2004, a consensus statement regarding the diagnosis and treatment of GI NETs was published on behalf of the European Neuroendocrine Tumor Society, which details site-specific approaches to the diagnosis of GI carcinoids.
Factors that determine the clinical course and outcome of patients with GI carcinoid tumors are complex and multifaceted and include the following:
- The site of origin.
- The size of the primary tumor.
- The anatomical extent of disease.
Elevated expression of the proliferation antigen Ki-67 and the tumor suppressor protein p53 have been associated with poorer prognosis; however, some investigators suggest that the Ki-67 index may be helpful in establishing prognosis of gastric lesions only and maintain that no consistent genetic markers of prognosis have yet been discovered. Adverse clinical prognostic indicators include:
- Carcinoid syndrome.
- Carcinoid heart disease.
- High concentrations of the tumor markers urinary 5-HIAA and plasma chromogranin A.
In general, patients with carcinoid tumors of the appendix and rectum experience longer survival than patients with tumors arising from the stomach, small intestine, and colon. Carcinoid tumors occurring in the small intestine, even those of small size, have a greater propensity to metastasize than those in the appendix, colon, and rectum. Appendiceal and rectal carcinoids are usually small at the time of initial detection, and have rarely metastasized. The presence of metastases has been associated with a reduction in 5-year survival ranging from 39% to 60% in several case series and reviews.[3,68,69,70,71] However, some patients with metastatic carcinoid tumors have an indolent clinical course with survival of several years, whereas others experience an aggressively malignant course with short survival. Although metastases are associated with a shorter survival in large patient samples, the presence of metastases alone does not sufficiently predict the clinical course of the individual patient.
Approximately 35% of carcinoids of the small intestine are associated with carcinoid syndrome. The relatively common carcinoids of the appendix and rectum rarely produce this syndrome, and carcinoids from other sites have intermediate risks.[71,72] Investigations using echocardiographic criteria for carcinoid heart disease found prevalences ranging from 35% to 77% among patients with carcinoid syndrome.[73,74,75,76,77] The tricuspid valve is affected more frequently and severely than the pulmonic valve, and the presence and severity of carcinoid heart disease, particularly tricuspid valve dysfunction, is associated with shortened survival.[74,76,77,78] One study involving 64 patients with midgut carcinoid syndrome found 5-year survival rates of 30% for those with severe carcinoid heart disease versus 75% for those with no cardiac disease.