History

Fact Explanation
Flushing Carcinoid syndrome is the bio-chemical manifestation of a carcinoid tumor [1], which is a slow-growing tumor of neuro-endocrine origin [2]. The bio-chemical substances secreted (mainly serotonin) by the tumor gives rise to clinical features of the carcinoid syndrome. Only 10% of patients get the carcinoid syndrome when the tumor has metastasized to lungs/liver, when these organs are no longer able to metabolize the substances secreted by the carcinoid tumor. Flushing is a vaso-active symptom caused by vaso dilation by these secretory substances [2].
Diarrhea/ passage of loose stools Diarrhea is thought to be caused by the excitatory effect of serotonin on the smooth muscle causing increased gastro-intestinal motility [3].
Symptoms of right heart failure (ankle & abdominal swelling/fatigue/ exertional dyspnea) Right heart failure is a consequence of right side valvular heart disease (pulmonary stenosis/ tricuspid insufficiency) caused by the prolonged exposure of the endocardium to serotonin. Hence this is a late effect of carcinoid syndrome. Serotonin causes endocardial fibrosis resulting in the valvular defects and ultimately right heart failure [2]. Note: left side valves are affected less as serotonin is metabolized by the lungs [1].
New onset wheezing This is due to bronchospasm caused by serotonin & bradykinin secreted by the tumor [4]. Note: the above symptoms can be precipitated by exertion or by consuming food that are high in tyramine (blue cheese/chocolate) or ethanol (red wine) [5].
Family history of parathyroid/ pancreatic/ bronchial/ gastric/pituitary & adrenal tumors This should raise the suspicion of multiple endocrine neoplasia (MEN-1), which has a genetic susceptibility to carcinoid tumors [5]. Most patients initially present with symptoms of hypercalcemia due to parathyroid disease [2]. Note: patients with MEN-1 present about 15 years earlier than the sporadic cases with carcinoid tumor [6].
Family history of hemangioblastomas of the central nervous system/pancreatic tumors/ retinal angiomas/ renal cell carcinomas & phechromocytomas This should raise the suspicion of Von Hippel Lindau’s disease (VHL) ), which has a genetic susceptibility to carcinoid tumors [5].
Family history of parathyroid/medullary thyroid cancer/ phechromocytomas and skin lumps/ depigmented lesions These findings lead to the possibility of Neurofibromatosis type 1 (NF-1) which is associated with mid gut carcinoid tumors [5]. As the carcinoid syndrome is highly associated with small bowel carcinoid tumors which are a derivative of the mid gut [2], asking about NF-1from the patient is very important in taking history.
References
  1. DE VRIES H, VERSCHUEREN RC, WILLEMSE PH, KEMA IP, DE VRIES EG. Diagnostic, surgical and medical aspect of the midgut carcinoids. Cancer Treat Rev [online] 2002 Feb, 28(1):11-25 [viewed 02 September 2014] Available from: doi:10.1053/ctrv.2001.0239
  2. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  3. HAGE R, DE LA RIVIèRE AB, SELDENRIJK CA, VAN DEN BOSCH JM. Update in pulmonary carcinoid tumors: a review article. Ann Surg Oncol [online] 2003 Jul, 10(6):697-704 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12839856
  4. HORTON KM, KAMEL I, HOFMANN L, FISHMAN EK. Carcinoid tumors of the small bowel: a multitechnique imaging approach. AJR Am J Roentgenol [online] 2004 Mar, 182(3):559-67 [viewed 02 September 2014] Available from: doi:10.2214/ajr.182.3.1820559
  5. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575
  6. MODLIN IM, LYE KD, KIDD M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer [online] 2003 Feb 15, 97(4):934-59 [viewed 02 September 2014] Available from: doi:10.1002/cncr.11105

Examination

Fact Explanation
Tachycardia & hypotension Caused by the various vaso-active substances secreted by the carcinoid tumor. Some of these substances include serotonin, bradykinin, prostaglandins & substance P [1].
Heart murmur Ejection click/ ejection systolic murmur at the right 2nd intercostal space of pulmonary stenosis or pansystolic murmur at the lower sternal edge of tricuspid insufficiency may be heard [1].
Signs of right heart failure (bilateral ankle edema/ ascites/ tender hepatomegaly/ elevated jugular venous pulse) These can be found as a complication of pulmonary stenosis/ tricuspid insufficiency, at the late stages of carcinoid tumor as prolonged exposure to excessive serotonin is needed to cause endocardial fibrosis resulting in the valve defects [1].
Signs of bronchospasm in chest examination Signs similar to asthma may be seen due to bronchospasm induced by serotonin [1]. the signs include hyper-resonance on percussion, rhochi & prolonged expiration with wheezing on auscultation.
Hepatosplenomegaly on abdominal examination This can be a finding in the presence of metastatic disease.
Skin lumps (fibromas/lipomas/neurofibromas) and associated lesions Presence of fibromas & lipomas raise the suspicion of MEN-1 while neurofibromas associated with café-au-lait spots & axillary freckles suggest a diagnosis of NF-1, both of which are susceptible genetic conditions for carcinoid tumors [3].
References
  1. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  2. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575

Differential Diagnoses

Fact Explanation
Menopausal syndrome When women around 50 years of age present with flushing as the predominant symptom, it may be regarded as a feature of menopause instead of carcinoid syndrome [1].
Benign cutaneous flushing This also causes flushing but not the other hormonal effects of the carcinoid syndrome [1].
Bronchial asthma As bronchospasm is also caused by serotonin in the carcinoid syndrome, asthma comes as a main differential diagnosis [1]. History can help in making the diagnosis as there is often a triggering factor and a positive family history of atopy in asthma.
Gartroenteritis Causes diarrhea similar to carcinoid syndrome, but is associated with ill health such as malaise & fever unlike in carcinoid syndrome [1]. Also the gastroenteritis resolves in few days with full recovery.
Inflammatory bowel disease This also causes chronic diarrhea [1]. The distinguishing clinical features from carcinoid syndrome are bleeding per rectum, fistula formation and presence of extra intestinal features such as erythema nodosum, clubbing & sacroilietis [2].
Rheumatic heart disease This is mostly seen in developing countries. Rheumatic heart disease affects mainly on the left side valves (most common mitral valve) [3] whereas carcinoid syndrome affects the right side valves [1].
Infective endocarditis This also leads to valve defects but is associated with systemic features as high fever, malaise and splinter hemorrhages, osler’s nodes and janeway lesions. Cardiac echogram will reveal vegetations on valve cusps and a positive blood culture along with the short duration of progression of the disease will help in making the diagnosis [4].
Anaphylaxis This causes rapid onset breathing difficulty with wheezing caused by bronchospasm [1]. The sudden onset of symptoms together with a history of ingestion of a precipitant will help in making the diagnosis.
References
  1. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  2. WILKINS T, JARVIS K, PATEL J. Diagnosis and management of Crohn's disease. Am Fam Physician [online] 2011 Dec 15, 84(12):1365-75 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22230271
  3. CARABELLO BA, CRAWFORD FA JR. Valvular heart disease. N Engl J Med [online] 1997 Jul 3, 337(1):32-41 [viewed 02 September 2014] Available from: doi:10.1056/NEJM199707033370107
  4. PIERCE D, CALKINS BC, THORNTON K. Infectious endocarditis: diagnosis and treatment. Am Fam Physician [online] 2012 May 15, 85(10):981-6 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22612050

Investigations - for Diagnosis

Fact Explanation
Serum analysis Serum analysis of chromogranin A is the ideal test to confirm the disease as it is almost always elevated in neuro-endocrine tumors [1], hence has high specificity [2]. False positives can be seen in multiple myeloma [2]. Plasma pancreatic polypeptide and human chorionic gonadotrophin alpha subunits are other serum markers [1]. Measurement of insulin, gastrin,glucagons and other peptides can be carried out depending on the clinical features [3]. ].
Urinanalysis Measuring urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) is recommended for patients presenting with vasoactive symptoms (flushing), which is a metabolite of serotonin [4]. Measuring 5-HIAA in a 24 hour urine sample is the most common test done to detect excessive serotonin secretion in the carcinoid syndrome [2]. However, the patient should refrain from taking food & medication rich in serotonin prior to the test, to prevent from getting a false positive result.
Imaging Imaging modality depends on the suspected site of the carcinoid tumor [4]. Barium contrast studies: may detect mucosal thickening/ submucosal mass/luminal narrowing [5]. Computed tomography (CT): may detect mucosal thickening/ submucosal mass/luminal narrowing. Infiltrated carcinoids show a characteristic stellate pattern on CT [5]. CT has higher sensitivity in detecting carcinoid tumors of the thymus and bronchus than other imaging modalities[1]. CT may also be useful in detecting second primary malignancy, which is a significant feature of carcinoid syndrome. The common sites are the gastro-intestinal tract, genitor-urinary tract and the respiratory tract [6]. Note: CT is very important in diagnosing carcinoid syndrome as it shows liver mets that supports the diagnosis. CT also shows mesenteric extension [2]. Magnetic resonance imaging (MRI): imaging results of carcinoid tumor is similar to that of CT [7]. Endoscopic ultrasonography (EUS): important in assessing the regional spread of the tumor, as it gives an account of local tumor invasion and lymph node metastases. EUS is indicated in thymic, bronchopulmonary, gastroduodenal and pancreatic tumors [1]. Note: all those imaging modalities can detect liver mets of size more than 1 cm, hence very important in patients with carcinoid syndrome [1]. USS & CT also helps in taking specimens for histopathological diagnosis [8].
Nuclear medicine Iodine labeled meta-iodobenzylguanidine (MIBG) [7] and positron emission tomography (PET) [9] can be used to detect neuroendocrine tumors.
Somatostatin receptor scintigraphy Neuro-endocrine cells containing receptors for somatostatin and other peptides is the basis for this test [1]. This is superior to CT & MIBG and has greater than 90% sensitivity to patients with symptoms of carcinoid syndrome [10]. Note: tumors lacking somatostatin receptors such as benign insulinomas can escape from this test [1].
Histopathological diagnosis Observation of the characteristic cells by histopathology confirms the diagnosis [1]. Surgical / coarse biopsy needle specimens give detailed appearance of the cells by light/electron microscopy whereas fine needle aspiration cytology (FNAC) specimens are unable to do so. Immunohistochemical analyses (ICA) using chromogranin A and synaptophysin as markers give a more accurate histopathological diagnosis [1]. Tyramide Signal amplification procedure augments the sensitivity of ICA and helps in the diagnosis of poorly differentiated neuro-endocrine tumors [1].
References
  1. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575
  2. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  3. ERIKSSON B, OBERG K, STRIDSBERG M. Tumor markers in neuroendocrine tumors. Digestion [online] 2000:33-8 [viewed 02 September 2014] Available from: doi:51853
  4. RAMAGE JK, DAVIES AH, ARDILL J, BAX N, CAPLIN M, GROSSMAN A, HAWKINS R, MCNICOL AM, REED N, SUTTON R, THAKKER R, AYLWIN S, BREEN D, BRITTON K, BUCHANAN K, CORRIE P, GILLAMS A, LEWINGTON V, MCCANCE D, MEERAN K, WATKINSON A, UKNETWORK FOR NEUROENDOCRINE TUMOURS. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut [online] 2005 Jun:iv1-16 [viewed 02 September 2014] Available from: doi:10.1136/gut.2004.053314
  5. KULKE MH, MAYER RJ. Carcinoid tumors. N Engl J Med [online] 1999 Mar 18, 340(11):858-68 [viewed 02 September 2014] Available from: doi:10.1056/NEJM199903183401107
  6. HABAL N, SIMS C, BILCHIK AJ. Gastrointestinal carcinoid tumors and second primary malignancies. J Surg Oncol [online] 2000 Dec, 75(4):310-6 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11135275
  7. HORTON KM, KAMEL I, HOFMANN L, FISHMAN EK. Carcinoid tumors of the small bowel: a multitechnique imaging approach. AJR Am J Roentgenol [online] 2004 Mar, 182(3):559-67 [viewed 02 September 2014] Available from: doi:10.2214/ajr.182.3.1820559
  8. PASIEKA JL, MCKINNON JG, KINNEAR S, YELLE CA, NUMEROW L, PATERSON A, RORSTAD O, DIFRANCESCO LM, MCEWAN A, SKOGSEID B. Carcinoid syndrome symposium on treatment modalities for gastrointestinal carcinoid tumours: symposium summary. Can J Surg [online] 2001 Feb, 44(1):25-32 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11220795
  9. SUNDIN A, ERIKSSON B, BERGSTRöM M, LåNGSTRöM B, OBERG K, ORLEFORS H. PET in the diagnosis of neuroendocrine tumors. Ann N Y Acad Sci [online] 2004 Apr:246-57 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15153441
  10. KALTSAS G, KORBONITS M, HEINTZ E, MUKHERJEE JJ, JENKINS PJ, CHEW SL, REZNEK R, MONSON JP, BESSER GM, FOLEY R, BRITTON KE, GROSSMAN AB. Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors. J Clin Endocrinol Metab [online] 2001 Feb, 86(2):895-902 [viewed 02 September 2014] Available from: doi:10.1210/jcem.86.2.7194

Investigations - Fitness for Management

Fact Explanation
Full blood count (FBC) Investigation to asses basic fitness are needed as patients with carcinoid syndrome may undergo surgery to remove the tumor [1]. Hemoglobin level is the most important component in the FBC as correction of anemia is required before surgery to prevent effects of bleeding related complications.
Electrocardiogram (ECG) & echogram Important to asses fitness for surgery, as morbidity & mortality is high in patients with poor cardio-resoiratory reserve [2]. ECG should be done in every patient to detect rhythm abnormalities that can be aggrevated during surgery, while echo can be reserved for patents with co-morbodities.
Spirometry Used to asses the pulmonary function before surgery as abdominal surgery may cause basal atelectasis followed by chest infection (pneumonia). Although this is carried out as a routine test prior to abdominal surgery, the actual effect of it in the assesment of pulmonary function remains controversial [3].
Serum creatinine & blood urea These are used as a general guide to asses the renal functions prior to surgery,
Fasting blood sugar (FBS) & lipid profile Used to asses co-existing diabetes & dyslipidemia. Note: control of blood glucose is very crucial in the post-operative period for good wound healing and prevention of infection [4].
Liver profile This is important in the surgery of carcinoid tumor, specially if the surgery is carried out for hapatic matastases, to have a baseline value of liver function before surgery.
References
  1. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575
  2. STRUTHERS R., ERASMUS P., HOLMES K., WARMAN P., COLLINGWOOD A., SNEYD J. R.. Assessing fitness for surgery: a comparison of questionnaire, incremental shuttle walk, and cardiopulmonary exercise testing in general surgical patients. British Journal of Anaesthesia [online] December, 101(6):774-780 [viewed 05 September 2014] Available from: doi:10.1093/bja/aen310
  3. LAWRENCE VALERIE A.. Preoperative Spirometry Before Abdominal Operations. Arch Intern Med [online] 1989 February [viewed 05 September 2014] Available from: doi:10.1001/archinte.1989.00390020030006
  4. MCMURRY JF JR. Wound healing with diabetes mellitus. Better glucose control for better wound healing in diabetes. Surg Clin North Am [online] 1984 Aug, 64(4):769-78 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6433493

Investigations - Followup

Fact Explanation
Serum analysis of chromogranin A This is used to follow up the course of the disease as it is highly specific to carcinoid tumor [1] and is almost always elevated in carcinoid tumors [2].
References
  1. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  2. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575

Investigations - Screening/Staging

Fact Explanation
Fine needle aspiration cytology (FNAC) Can be used as a screening test of the tumor as it aids in detecting granulated neoplastic neuroendocrine cells [1].
Somatostatin receptor scintigraphy Neuro-endocrine cells containing receptors for somatostatin and other peptides is the basis for this test. As this is a whole-body investigation it helps in staging of the disease [1]. Note: the above staging tests are for the carcinoid tumor, not the carcinoid syndrome which is only a cliical manifestation of the carcinoid tumor.
References
  1. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575

Management - General Measures

Fact Explanation
Patient education Explaining the patient about the disease condition & related counselling is of utmost importance as carcinoid syndrome occur in the later stage of carcinoid tumor with the matastatic disease [1], and mostly symptomatic treatment is carried out.
Treatment of heart failure: Diuretics are used and occasionally valvular replacement is carried out [1].
Flushing: Advice to avoid precipitating food & alcohol. Use of serotonin antagonists and somatostatin analogues, interferon can be beneficial. Hepatic artery embolization also may be effective [1].
Diarrhea: Anti-diarrheal agents, serotonin antagonists and somatostatin analogues, interferon and hepatic artery embolization can be effective [1].
Wheezing: Bronchodilators, serotonin antagonists and somatostatin analogues, interferon and hepatic artery embolization can be effective [1].
References
  1. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  2. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575

Management - Specific Treatments

Fact Explanation
Surgery Treatment options vary on the tumor site and the presence of metastasis [1]. Surgical resection is the only curative method of neuro-endocrine tumors. Debulking and bypassing procedures for metastatic disease facilitates medical treatment [2]. Radiofrequency ablation is a more aggressive type of surgery to remove the tumor. Metastases are treated with laser treatment [2].
Management of hepatic metastases Carcinoid syndrome is an indication for surgery of liver mets which can be performed either with curative or palliative intent. The types of resection include enucleation, segmental resection, hemi-hepatectomy and extended hemi-hepatectomy, depending on the site combined with radio-frequency ablation. Liver transplantation has been performed in young patients with no extrahepatic tumor tissue, but recurrence is reported almost always post surgery. Embolizationcan combined with cytotoxic therapy can also be carried out,which is a commonly used technique to treat clinical symptoms and hepatic mets. 5-fluorouracil, doxorubicin & mitomycin C are used for chemoemboliization and the symptomatic response takes about 15-30 months. Common side effects are post-embolization syndrome with nausea, right upper quadrant pain while major effects are gall bladder necrosis, pancreatitis, hepato-renal syndrome & liver absecess with a mortality rate of 7% [2]. Debulking surgery, radiofrequency ablation, cryoablation, laser therapy, chemoembolization & medical therapy are used to treat multiple liver mets [2]. Note: intra-operative USS should always be performed during surgery to detect all the mets and observe the relation to hepatic vessels & bile ducts [2].
Somatostatin analogues These are used to reduce the hormonal effect, hence the clinical features. They exert both cytotoxic & cytostatic actions and mediate cell cycle arrest and thereby prevent release of the peptides from neuro-endocrine cells. Octerotide & lanreotide are used and this is the primary mode of treatment for peptide-related symptoms. These are used to facilitate surgery as they reduce the risk of carcinoid crises. Possible side-effects are nausea, flatulence, diarrhea, steatorrhea and gall stones and substitution of pancreatic enzymes can reduce these symptoms [2].
Alpha-interferon Used to treat midgut carcinoids. It blocks the cell cycle and inhibit angiogenesis and has an indirect effect on the immune system as well. Combination with somatostatin analogues has a synergistic & additive effect by up regulating the somatostatin receptors. Side-effects include flu-like symptoms, chronic fatigue, depression, myositis & SLE syndrome [2].
Cytotoxic therapy The treatment of choice for highly proliferating neuro-endocrine tumors. Streptozotocin, 5-fluorouracil, cisplatinum and paraplatinum are some agents used. Common side-effects are nausea, vomiting and renal toxicity [2]. Important: combination therapy with somatostatin analogues is recommended for clinical syndromes associated with hormone overproduction, thus carcinoid syndrome can have a beneficial effect from this therapy [2].
Anti-angiogenic therapy This is a new option used based on the high vascularity of carcinoid tumors. Endostatin and angostatin are used to inhibit angiogenesis and thereby suppress tumor growth [2].
Tyrosine kinase inhibitors Imitanib and other inhibitors may be effective as some carcinoid tumors express tyrosine kinase receptors [2].
Radiotherapy As carcinoid tumors are radio-resistant, external beam therapy is used only for brain & bone metastases [2].
References
  1. ROBERTSON RG, GEIGER WJ, DAVIS NB. Carcinoid tumors. Am Fam Physician [online] 2006 Aug 1, 74(3):429-34 [viewed 02 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16913162
  2. ÖBERG KJELL, ASTRUP LONE, ERIKSSON BARBRO, FALKMER STURE E., FALKMER URSULA G., GUSTAFSEN JENS, HAGLUND CAJ, KNIGGE ULRICH, VATN MORTEN H., VäLIMäKI MATTI. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview. Acta Oncol [online] 2004 January, 43(7):617-625 [viewed 02 September 2014] Available from: doi:10.1080/02841860410018575