Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-A, somatostatin receptor scintigraphy and somatostatin analogues.

BACKGROUND/AIMS: Carcinoids are relatively rare tumors that arise from neuroendocrine cells and have proved to be slow growing malignancies which involve many organs and most frequently the gastrointestinal (GI) tract. Herein we present in this study 101 pts with carcinoid tumors that originated from the GI tract and pancreas. Also, we analyze the clinical and pathological features, pointing out the characteristics of this group of neoplasms and describing our diagnostic and therapeutical approach, in parallel with a brief review of the literature.
METHODOLOGY: One hundred and one (66 females and 35 males, aged from 16 to 79 years) pts were included in our study. The primary tumors originated from the GI tract in 97/101 pts (appendix 34%, small intestine 31%, stomach 14%, duodenum 6%, colon 6%, rectum 3%) and from the pancreas in 4/101 (4%). The diagnosis was confirmed histologically in all cases, after surgical excision of the primary tumor or by biopsies taken during endoscopy. All pts were evaluated several times per year with clinical, biochemical and imaging assessments, including neuroendocrine markers [urinary 5-Hydroxyindoleacetic acid (5-HIAA), serum Chromogranin-A (CgA)] and Somatostatin Receptor Scintigraphy (OCTREOSCAN). The follow-up period ranged between 1.5 to 12.5 years (mean time: 5 years and 3 months) and it is still in progress.
RESULTS: Patients were referred to us with gastrointestinal symptoms or symptoms of the "carcinoid syndrome" (flushing, and diarrhea), depending mainly on the location of the primary tumors and the existence or not of metastases. CgA and 5-HIAA levels were increased especially in metastatic tumors. Localization of the primary tumors to facilitate surgery was made by many imaging techniques (US, CT, MRI, Enteroclysis, OCTREOSCAN) and endoscopic procedures. OCTREOSCAN was positive in 94% pts with metastatic disease. Furthermore, it revealed the primary and the metastatic lesions in 16% and 33% of pts with carcinoids of the small intestine respectively, while other conventional imaging procedures (including MRI) were negative at the same time. Seventy-four percent of the pts underwent a surgical resection of the primary tumor, while in 21%, an endoscopic polypectomy was performed. All pts with metastatic tumors and positive OCTREOSCAN, were treated with Somatostatin analogues, which resulted in control of symptoms (75%), stabilization of tumor growth (71%) or tumor shrinkage (9%). A combined therapy with the addition of interferon-a was initiated in pts in whom, despite the increase of drug dosage and the shortening of administration intervals, a complete clinical and biochemical response was no more achieved with Somatostatin analogues alone. Pancreatic carcinoids and also those that originated from the proximal colon were found to have worst prognosis.
CONCLUSIONS: a) Tumor size (especially in appendiceal and gastric carcinoids) and, also, the dispersion of disease, highly predict the evolution of the patients; b) serum Chromogranin-A seems to be a very useful tumor marker for the diagnosis and follow-up of pts with GI carcinoids; c) the introduction of new imaging techniques and especially OCTREOSCAN contributes to a better localization of the primary tumors and their metastases, as well as, to the right decision of the appropriate medical treatment; d) surgical excision is the treatment of choice in nonmetastatic tumors; and e) in pts with metastatic disease, the administration of Somatostatin analogues improves their quality of life.