Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms.
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Endocrine pancreatic tumors (EPT) and neuroendocrine tumors (NET) occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). We analyzed the frequency of allelic deletions and mutations of the recently identified MEN1 gene in 53 sporadic tumors including 30 EPT and 23 NET (carcinoids) of different locations and types. Allelic deletion of the MEN1 locus was identified in 18/49 (36.7%) tumors (13/30, 43.3% in EPT and 5/19, 26.3% in NET) and mutations of the MEN1 gene were present in 8/52 (15.3%) tumors (4/30 (13.3%) EPT and 4/22 (18.1%) NET). The somatic mutations were clustered in the 5' region of the coding sequence and most frequently encompassed missense mutations. All tumors with mutations exhibited a loss of the other allele and a wild-type sequence of the MEN1 gene in nontumorous DNA. In one additional patient with a NET of the lung and no clinical signs or history of MEN1, a 5178-9G-->A splice donor site mutation in intron 4 was identified in both the tumor and blood DNA, indicating the presence of a thus far unknown MEN1 syndrome. In most tumor groups the frequency of allelic deletions at 11q13 was 2 to 3 times higher than the frequency of identified MEN1 gene mutations. Some tumor types, including rare forms of EPT and NET of the duodenum and small intestine, exhibited mutations more frequently than other types. Furthermore, somatic mutations were not restricted to foregut tumors but were also detectable in a midgut tumor (15.2% versus 16.6%). Our data indicate that somatic MEN1 gene mutations contribute to a subset of sporadic EPT and NET, including midgut tumors. Because the frequency of mutations varies significantly among the investigated tumor subgroups and allelic deletions are 2 to 3 times more frequently observed, factors other than MEN1 gene inactivation, including other tumor-suppressor genes on 11q13, may also be involved in the tumorigenesis of these neoplasms. (+info)
Carcinoids of the common bile duct: a case report and literature review.
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Carcinoids of the extrahepatic bile ducts and particularly the common bile duct are extremely rare. A 65-year-old woman presented with obstructive jaundice. Laboratory and imaging studies gave results that were consistent with an obstructing lesion in the common bile duct. In this case, a stent was inserted initially to decompress the bile ducts. Subsequently a laparotomy and pancreaticoduodenectomy were performed and a tissue diagnosis of carcinoid of the common bile duct was made. The patient was well with no evidence of recurrence 17 months postoperatively. The authors believe this is the 19th reported case of an extrahepatic bile duct carcinoid. (+info)
Primary hepatic carcinoid in a renal transplant patient.
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There seems to be a world-wide increase in the incidence of tumors among immunosuppressed patients. Of 1350 renal allografts transplanted in the past 23 years at the Department of Transplantation and Surgery, 56 cases were malignant tumors. The case of a 58-year-old female patient is reported, with disseminated primary carcinoid in the liver detected 86 days after renal transplantation. According to the literature only 39 patients with primary liver carcinoids have been reported until 1997, but this is the first where the carcinoid developed in an immunosuppressed patient. The rapid progression of the carcinoid could be associated with the immunosuppression. (+info)
Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome.
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PURPOSE: Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea and flushing associated with carcinoid syndrome but requires long-term multiple injections daily. A microencapsulated long-acting formulation (LAR) of octreotide acetate has been developed for once-monthly intramuscular dosing. PATIENTS AND METHODS: A randomized trial compared double-blinded octreotide LAR at 10, 20, and 30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and who returned for at least the week 20 evaluation constituted the efficacy-assessable population. RESULTS: Complete or partial treatment success was comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg, 71.4%; 30 mg, 61.9%; P> or =.72 for all pairwise comparisons). Control of stool frequency was similar in all treatment groups. Flushing episodes were best controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least effective in the control of flushing. Treatment was well tolerated by patients in all four groups. CONCLUSION: Once octreotide steady-state concentrations are achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended. Supplemental SC octreotide is needed for approximately 2 weeks after initiation of octreotide LAR treatment. Occasional rescue SC injections may be required for possibly 2 to 3 months until steady-state octreotide levels from the LAR formulation are achieved. (+info)
Primary carcinoid tumor of the testis: immunohistochemical, ultrastructural and DNA flow cytometric study of two cases.
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Primary testicular carcinoid tumor, occupying 0.23% of testicular neoplasm, is a rare and indolent neoplasm with the potential for distant metastasis. We present two cases of primary pure carcinoid tumor of the testis. Both patients were 36 years old. Physical examination revealed testicular mass with and without tenderness. The preoperative serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein were normal and neither patient had carcinoid syndrome. The tumors measured 7.5x6x4 cm and 5.5x5x4 cm in size. Histologically, immunohistochemically and ultrastructurally, the tumors showed typical features of the carcinoid tumor. Case 1 showed extensive tumor necrosis and vascular invasion. DNA flow cytometric analysis showed aneuploidy with DNA index of 1.47 and S+G2M of 14.0% in case 1 and tetraploidy with DNA index of 1.96 and S+G2M of 22.1% in case 2. Both patients have been well without any signs of metastasis after operation for 24 months in case 1 and for 16 months in case 2. (+info)
Library of sequence-specific radioimmunoassays for human chromogranin A.
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BACKGROUND: Human chromogranin A (CgA) is an acidic protein widely expressed in neuroendocrine tissue and tumors. The extensive tissue- and tumor-specific cleavages of CgA at basic cleavage sites produce multiple peptides. METHODS: We have developed a library of RIAs specific for different epitopes, including the NH2 and COOH termini and three sequences adjacent to dibasic sites in the remaining part of CgA. RESULTS: The antisera raised against CgA(210-222) and CgA(340-348) required a free NH2 terminus for binding. All antisera displayed high titers, high indexes of heterogeneity ( approximately 1.0), and high binding affinities (Keff0 approximately 0.1 x 10(12) to 1.0 x 10(12) L/mol), implying that the RIAs were monospecific and sensitive. The concentration of CgA in different tissues varied with the assay used. Hence, in a carcinoid tumor the concentration varied from 0.5 to 34.0 nmol/g tissue depending on the specificity of the CgA assay. The lowest concentration in all tumors was measured with the assay specific for the NH2 terminus of CgA. This is consistent with the relatively low concentrations measured in plasma from carcinoid tumor patients by the N-terminal assay, whereas the assays using antisera raised against CgA(210-222) and CgA(340-348) measured increased concentrations. CONCLUSION: Only some CgA assays appear useful for diagnosis of neuroendocrine tumors, but the entire library is valuable for studies of the expression and processing of human CgA. (+info)
Review article: current status of gastrointestinal carcinoids.
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Carcinoid tumours are enigmatic, slow growing malignancies which occur most frequently (74%) in the gastrointestinal tract. In recent years, it has become apparent that the term 'carcinoid' represents a wide spectrum of different neoplasms originating from a variety of different neuroendocrine cell types. Carcinoid lesions are usually identified histologically by their affinity for silver salts, by general neuroendocrine markers, or more specifically by immunocytochemistry using antibodies against their specific cellular products. Within the gut, the most frequent sites are the small bowel (29%), the appendix (19%) and rectum (13%). Clinical manifestations are often vague or absent. Nevertheless, in approximately 10% of patients the tumours secrete bioactive mediators which may engender various elements of characteristic carcinoid syndrome. In many instances the neoplasms are detected incidentally at the time of surgery for other gastrointestinal disorders. The tendency for metastatic spread correlates with tumour size, and is substantially higher in lesions larger than 2.0 cm. An association with noncarcinoid neoplasms is ascribed in 8-17% of lesions. Treatment consists of radical surgical excision of the tumour, although gastric (type I and II) and rectal carcinoids may be managed with local excision. Overall 5-year survival is excellent for carcinoids of the appendix (86%) and rectum (72%), whereas small intestinal (55%), gastric (49%) and colonic carcinoids (42%) exhibit a far worse prognosis. (+info)
Clinical symptoms, hormone profiles, treatment, and prognosis in patients with gastric carcinoids.
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BACKGROUND: Type 1 gastric carcinoids are associated with hypergastrinaemia and chronic atrophic gastritis, type 2 occur in patients with multiple endocrine neoplasia type 1 combined with Zollinger-Ellison syndrome, and type 3 lack any relation to hypergastrinaemia. Type 1 tumours are usually benign whereas type 3 are highly malignant. AIMS: To identify possible tumour markers in patients with gastric carcinoids. PATIENTS/METHOD: Nine patients with type 1, one with type 2, and five with type 3 were evaluated with regard to symptoms, hormone profile, and prognosis. RESULTS: Plasma chromogranin A was increased in all patients but was higher (p < 0.01) in those with type 3 than those with type 1 carcinoids. All patients with type 3 carcinoids died from metastatic disease, but none of the type 1 patients died as a result of their tumours. One type 1 patient with a solitary liver metastasis received interferon alpha and octreotide treatment. Nine months later, the metastasis was no longer detectable. She is still alive eight years after diagnosis, without recurrent disease. This represents the only reported case of foregut carcinoid with an unresectable liver metastasis that seems to be have been cured by biotherapy. CONCLUSIONS: Plasma chromogranin A appears to be a valuable tumour marker for all types of gastric carcinoid. Combination therapy with interferon alpha and octreotide may be beneficial in patients with metastasising type 1 gastric carcinoids. (+info)