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5. Carcinoid Tumour Biochemical And Radiological Testing

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5. Carcinoid Tumour Biochemical And Radiological Testing

  1. 1. Carcinoid Tumour Biochemical and Radiological Testing Gillian Harris 4th year MBBS
  2. 2. Carcinoid Tumour-background • Rare, slow growing • Derived from resident neuroendocrine cells • Most often found in GIT (2/3) and lung • Secrete various substances including -Serotonin -Histamine -Bradykinin -Prostaglandins -Kallikrein -Adrenocorticotropic hormone -Neuropeptide K -Gastrin -Neurokinins A & B -Calcitonin -Substance P -Growth hormone • Carcinoid syndrome
  3. 3. Biochemical Markers • 5-hydroxy-indole-acetic acid (5-HIAA) – End product of serotonin metabolism – Measured in 24 hour urinary collection – Sensitivity 75% Specificity 100% • Chromogranin A (CgA) – In wall of synaptic vesicles that store serotonin and glucagons – Levels correlate with tumour bulk – Elevated in 85-100% pts with carcinoid tumour – Sensitivity 67.9% Specificity 85.7%
  4. 4. 5-hydroxy-indole-acetic acid (5-HIAA) • End product of serotonin metabolism • Normal rate of excretion 2-8mg/day • Sensitivity of 73% • Specificity of 100%
  5. 5. Serotonin overproduction • Increased values of Urinary 5-HIAA secretion occur with: – Malabsorption syndromes – Ingestion of tryptophan-rich foods (eg bananas and avocadoes) – Certain drugs
  6. 6. Other methods for measuring serotonin overproduction • Urinary Serotonin • Platelet concentration of serotonin
  7. 7. Chromogranin A (CgA) • Found in the wall of secretory vesicles of neuroendocrine cells • Widely distributed throughout the neuroendocrine system • Immunohistochemical staining can detect the presence of CgA in the circulation
  8. 8. • CgA is elevated in 85-100% pts with carcinoid tumour • Specificity 85.7% • Sensitivity 67.9% for neuroendocrine tumours
  9. 9. Other causes of increased serum CgA • Renal impairment • Liver Failure • Atrophic Gastritis • Irritable bowel disease • Proton pump inhibitors • Physical Stress
  10. 10. Diagnostic Imaging • Neuroendocrine tumours express: – Neuroamine uptake mechanisms – Specific receptors (eg. Somatostatin receptors) • Radiolabelled amines/peptides bound to suitable ligands target specific cells • Gamma camera visualises uptake • Improved localisation with simultaneous conventional imaging (eg. CT/MRI)
  11. 11. 111 In-Pentetreotide Scintigraphy • 111In-labelled somatostatin analogue • Concentrates in neuroendocrine and some non- neuroendocrine tumours containing somatostatin receptor subtypes 2 and 5 • 80-90% sensitivity for carcinoid tumours (10) • Identifies lesions not visualised on conventional imaging – 1/3-2/3 patients had additional localisations – 65 extra lesions found per 100 patients
  12. 12. (11) Van der Lely; De Herder. Carcinoid Syndrome: diagnosis and medical management Arq Bras Endocrinol Metab. 2005: 49:5
  13. 13. Meta-iodobenzylguanidine (MIBG) Scintigraphy • Guanidine derivative • Utilises Type 1 amine uptake mechanism of cell • Found in carcinoid and other neuroendocrine tumours • Uses 123I- or 131I-labelled MIBG • 123I-labelled MIBG has a superior image quality • Useful for tumours which do not have somatostatin receptors • Select patients for MIBG therapy
  14. 14. Conventional Imaging Modalities • CT • MRI • Transabdominal ultrasound • Endoscopy • Endoscopic ultrasound • Selective mesenteric angiography
  15. 15. Tumour type Imaging (12) Foregut Chest radiography-occasionally detects lesions CT/MRI-identification of primary tumour, lymph nodes, facilitates biopsy diagnosis Octreotide Scintigraphy-negative in 30% but most specific Midgut Octreotide Scintigraphy-staging and identification of primary lesion. 83% diagnostic accuracy, 100% PPV Transabdominal Ultrasound-1/3 Small bowel carcinoids, 2/3 liver metastases CT/MRI-to monitor responsiveness to treatment, only detect 50% primary tumours Double contrast barium studies-to assess for imminent obstruction Hindgut Octreotide scintigraphy-highest sensitivity MIBG-when negative scan Endoscopic ultrasound-90% accuracy for localisation and staging of colorectal carcinoids MRI
  16. 16. Positron Emission Tomography (PET) • Carcinoids are slow growing, well differentiated tumours • FDG has detection rates 25-73% • Newer tracers: – 11 C-5-HTP – 68 Ga coupled to octreotide • More evidence necessary
  17. 17. Summary • Biochemical Markers – 5-hydroxy-indole-acetic acid (5-HIAA) – Chromogranin A (CgA) • Radiological Imaging – 111In-Pentetreotide Scintigraphy – Meta-iodobenzylguanidine (MIBG) Scintigraphy – Conventional Imaging (CT/MRI/Ultrasound) – PET
  18. 18. References • Feldman JM Urinary Serotonin in the Diagnosis of Carcinoid Tumors. Clin Chem 1986; 32:840 • Feldman JM, O’Doriso TM. Role of Neuropeoptides and Serotonin in the Diagnosis of Carcinoid Tumors. Am J Med 1986; 81:41 • Maroun J, Kocha W et al Guidelines for the diagnosis and management of carcinoid tumours. Current Oncology. 13(2): 67-76 • Janson ET, Holmberg L. Carcinoid tumors: Analysis of prognostic factors and survival in 301 patients from a referral center. Annals of Oncology. 1997; 8:685-690 • Bajetta E, Ferrari L. Chromogranin A, Neuron Specific Enolase, Carcinoembryonic Antigen, and Hydroxyindole Acetic Acid Evaluation in Patients with Neuroendocrine Tumors. American Cancer Society. 1999; 86(5) 858 • Eriksson B, Oberg K. Tumor Markers in Neuroendocrine Tumors. Digestion 2000; 62(suppl 1):33-38 • Nobels FRE et al. Chromogranin A: its clinical value as marker of neuroendocrine tumours. European Journal of Clinical Investigation. 1998; 28: 431-440 • Stridsberg M, Eriksson B et al. A comparison between three commerical kits for chromogranin A measurements. J of Endocrinology. 2003; 177: 337-341 • Onaitis MW, Kirshbom PM et al. Gastrointestinal Carcinoids: Characteriszation by Site of Origin and Hormone Production. Annals of Surgery. 232(4): 549-546 • Kweekeboom DJ, Krenning MD. Somatostatin Receptor Scintigraphy in Patients with Carcinoid tumors. World J Surg. 1996; 20:157-161. • Van der Lely; De Herder. Carcinoid Syndrome: diagnosis and medical management Arq Bras Endocrinol Metab. 2005; 49:5 • Kaltsas G, Besser G. The diagnosis and medical management of Advanced Neuroendocrine Tumours. Endocrine Reviews 25(3):458-511 • Kaltsas G, Rockall A. Recent advances in radiological and radionuclide imaging and therapy of Neuroendocrine tumours. European Journal of Endocrinology. 2004; 151:15-27. • Kaltsas G, Korbonits M. Comparison of Somatostatin Analog and Meta-Iodobenzylguanidine Radionuclides in the Diagnosis and Localization of Advanced Neuroendocrine Tumors. J Clin Endocrinology and Metab. 2001. 86(2) 895 • Sitaraman SV, Goldfinger SE. Diagnosis of the carcinoid syndrome. Uptodate. 2007.

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