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Small Bowel Neuroendocrine Tumors

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Surgical Endocrinopathies

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Abstract

Small bowel neuroendocrine tumors (NETs) are the most common neoplasm of the small intestine, and their incidence has increased in the past four decades. A majority of patients have metastatic disease at the time of diagnosis. Biochemical and imaging studies are important in the diagnostic workup and surveillance of small bowel NETs. Surgical resection of the primary tumor with regional lymph nodes and resection of metastatic lesions when possible is the only hope for cure and only possible in about 20 % of cases. In patients with unresectable metastasis, ablative/cytoreductive techniques exist which can achieve tumor control. Patients with systemic disease may be treated with somatostatin analogues as well as new emerging modalities such as peptide-receptor radiotherapy. Advancements in the treatment of metastatic lesions with ablative techniques and targeted medical therapy have improved survival.

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Abbreviations

CT Scan:

Computed tomography scan

MRI:

Magnetic resonance imaging

PET Scan:

Positron emission tomography

NETs:

Neuroendocrine tumors

WHO:

World Health Organization

NCDB:

National Cancer Database

SEER:

Surveillance Epidemiology and End Results

5-HIAA:

5-hydroxyindoleacetic acid

NCCN:

National Comprehensive Cancer Network

AJCC:

American Joint Committee on Cancer

TAE:

Transarterial embolization

TACE:

Transarterial chemoembolization

ENETS:

European Neuroendocrine Tumor Society

LITT:

Laser-induced thermotherapy

PRRT:

Peptide-receptor radiotherapy

References

  1. Strosberg J. Neuroendocrine tumours of the small intestine. Best Pract Res Clin Gastroenterol. 2012;26(6):755–73.

    Article  CAS  PubMed  Google Scholar 

  2. Lundqvist M, Wilander E. Subepithelial neuroendocrine cells and carcinoid tumours of the human small intestine and appendix. A comparative immunohistochemical study with regard to serotonin, neuron-specific enolase and S-100 protein reactivity. J Pathol. 1986;148(2):141–7.

    Article  CAS  PubMed  Google Scholar 

  3. Williams ED, Sandler M. The classification of carcinoid tum ours. Lancet. 1963;1(7275):238–9.

    Article  CAS  PubMed  Google Scholar 

  4. Maggard MA, O’Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg. 2004;240(1):117–22.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Cameron JL, Cameron AM. Small Bowel Carcinoid/ Neuroendocrine Tumors Current Surgical Therapy Elsevier Saunders 2011.

    Google Scholar 

  6. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72.

    Article  PubMed  Google Scholar 

  7. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59.

    Article  PubMed  Google Scholar 

  8. Norlén O, Stålberg P, Öberg K, Eriksson J, Hedberg J, Hessman O, et al. Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg. 2012;36(6):1419–31.

    Article  PubMed  Google Scholar 

  9. Thorson A, Biorck G, Bjorkman G, Waldenstrom J. Malignant carcinoid of the small intestine with metastases to the liver, valvular disease of the right side of the heart (pulmonary stenosis and tricuspid regurgitation without septal defects), peripheral vasomotor symptoms, bronchoconstriction, and an unusual type of cyanosis; a clinical and pathologic syndrome. Am Heart J. 1954;47(5):795–817.

    Article  CAS  PubMed  Google Scholar 

  10. Vinik AI, Silva MP, Woltering EA, Go VL, Warner R, Caplin M. Biochemical testing for neuroendocrine tumors. Pancreas. 2009;38(8):876–89.

    Article  PubMed  Google Scholar 

  11. Cunningham JL, Janson ET, Agarwal S, Grimelius L, Stridsberg M. Tachykinins in endocrine tumors and the carcinoid syndrome. Eur J Endocrinol. 2008;159(3):275–82.

    Article  CAS  PubMed  Google Scholar 

  12. Matuchansky C, Launay JM. Serotonin, catecholamines, and spontaneous midgut carcinoid flush: plasma studies from flushing and nonflushing sites. Gastroenterology. 1995;108(3):743–51.

    Article  CAS  PubMed  Google Scholar 

  13. von der Ohe MR, Camilleri M, Kvols LK. A 5HT3 antagonist corrects the postprandial colonic hypertonic response in carcinoid diarrhea. Gastroenterology. 1994;106(5):1184–9.

    PubMed  Google Scholar 

  14. Kvols LK. Metastatic carcinoid tumors and the malignant carcinoid syndrome. Ann N Y Acad Sci. 1994;733:464–70.

    Article  CAS  PubMed  Google Scholar 

  15. Lundin L, Norheim I, Landelius J, Oberg K, Theodorsson-Norheim E. Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities. Circulation. 1988;77(2):264–9.

    Article  CAS  PubMed  Google Scholar 

  16. Robiolio PA, Rigolin VH, Wilson JS, Harrison JK, Sanders LL, Bashore TM, et al. Carcinoid heart disease. Correlation of high serotonin levels with valvular abnormalities detected by cardiac catheterization and echocardiography. Circulation. 1995;92(4):790–5.

    Article  CAS  PubMed  Google Scholar 

  17. Zuetenhorst JM, Bonfrer JM, Korse CM, Bakker R, van Tinteren H, Taal BG. Carcinoid heart disease: the role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta and fibroblast growth factor. Cancer. 2003;97(7):1609–15.

    Article  CAS  PubMed  Google Scholar 

  18. Burke AP, Thomas RM, Elsayed AM, Sobin LH. Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer. 1997;79(6):1086–93.

    Article  CAS  PubMed  Google Scholar 

  19. Campana D, Nori F, Piscitelli L, Morselli-Labate AM, Pezzilli R, Corinaldesi R, et al. Chromogranin A: is it a useful marker of neuroendocrine tumors? J Clin Oncol. 2007;25(15):1967–73.

    Article  CAS  PubMed  Google Scholar 

  20. Conlon JM. Granin-derived peptides as diagnostic and prognostic markers for endocrine tumors. Regul Pept. 2010;165(1):5–11.

    Article  CAS  PubMed  Google Scholar 

  21. Sanduleanu S, De Bruine A, Stridsberg M, Jonkers D, Biemond I, Hameeteman W, et al. Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy. Eur J Clin Invest. 2001;31(9):802–11.

    Article  CAS  PubMed  Google Scholar 

  22. Yao JC, Pavel M, Phan AT, Kulke MH, Hoosen S, St Peter J, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011;96(12):3741–9.

    Article  CAS  PubMed  Google Scholar 

  23. Bajetta E, Ferrari L, Martinetti A, Celio L, Procopio G, Artale S, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer. 1999;86(5):858–65.

    Article  CAS  PubMed  Google Scholar 

  24. Ito T, Igarashi H, Jensen RT. Serum pancreastatin: the long sought universal, sensitive, specific tumor marker for neuroendocrine tumors? Pancreas. 2012;41(4):505–7.

    Article  PubMed Central  PubMed  Google Scholar 

  25. NCCN Guidelines: Neuroendocrine Tumors National Comprehensive Cancer Network, 2014.

    Google Scholar 

  26. Hakim FA, Alexander JA, Huprich JE, Grover M, Enders FT. CT-enterography may identify small bowel tumors not detected by capsule endoscopy: eight years experience at Mayo Clinic Rochester. Dig Dis Sci. 2011;56(10):2914–9.

    Article  PubMed  Google Scholar 

  27. Paulson EK, McDermott VG, Keogan MT, DeLong DM, Frederick MG, Nelson RC. Carcinoid metastases to the liver: role of triple-phase helical CT. Radiology. 1998;206(1):143–50.

    Article  CAS  PubMed  Google Scholar 

  28. Dromain C, de Baere T, Lumbroso J, Caillet H, Laplanche A, Boige V, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol. 2005;23(1):70–8.

    Article  PubMed  Google Scholar 

  29. Sundin A. Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2012;26(6):803–18.

    Article  PubMed  Google Scholar 

  30. Haug AR, Cindea-Drimus R, Auernhammer CJ, Reincke M, Wangler B, Uebleis C, et al. The role of 68 Ga-DOTATATE PET/CT in suspected neuroendocrine tumors. J Nucl Med. 2012;53(11):1686–92.

    Article  CAS  PubMed  Google Scholar 

  31. Garin E, Le Jeune F, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med. 2009;50(6):858–64.

    Article  CAS  PubMed  Google Scholar 

  32. Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16(3):978–85.

    Article  CAS  PubMed  Google Scholar 

  33. Rindi G, Kloppel G, Couvelard A, Komminoth P, Korner M, Lopes JM, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451(4):757–62.

    Article  CAS  PubMed  Google Scholar 

  34. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  35. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707–12.

    Article  PubMed  Google Scholar 

  36. Strosberg JR, Weber JM, Feldman M, Coppola D, Meredith K, Kvols LK. Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors. J Clin Oncol. 2013;31(4):420–5.

    Article  PubMed  Google Scholar 

  37. Figueiredo MN, Maggiori L, Gaujoux S, Couvelard A, Guedj N, Ruszniewski P, et al. Surgery for small-bowel neuroendocrine tumors: is there any benefit of the laparoscopic approach? Surg Endosc. 2014;28(5):1720–6.

    Article  PubMed  Google Scholar 

  38. Soreide O, Berstad T, Bakka A, Schrumpf E, Hanssen LE, Engh V, et al. Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery. 1992;111(1):48–54.

    CAS  PubMed  Google Scholar 

  39. Kulke MH, Benson AB, 3rd, Bergsland E, Berlin JD, Blaszkowsky LS, Choti MA, et al. Neuroendocrine tumors. J Natl Compr Canc Netw. 2012;10(6):724–64.

    CAS  PubMed  Google Scholar 

  40. Landry CS, Lin HY, Phan A, Charnsangavej C, Abdalla EK, Aloia T, et al. Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors. World J Surg. 2013;37(7):1695–700.

    Article  PubMed  Google Scholar 

  41. Wang YZ, Diebold A, Woltering E, King H, Boudreaux JP, Anthony LB, et al. Radioguided exploration facilitates surgical cytoreduction of neuroendocrine tumors. J Gastrointest Surg. 2012;16(3):635–40.

    Article  PubMed  Google Scholar 

  42. Steinmüller T, Kianmanesh R, Falconi M, Scarpa A, Taal B, Kwekkeboom DJ, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2008;87(1):47–62.

    Article  PubMed  Google Scholar 

  43. Chambers AJ, Pasieka JL, Dixon E, Rorstad O. The palliative benefit of aggressive surgical intervention for both hepatic and mesenteric metastases from neuroendocrine tumors. Surgery. 2008;144(4):645–51; discussion 51–3.

    Article  PubMed  Google Scholar 

  44. Pawlik TM, Izzo F, Cohen DS, Morris JS, Curley SA. Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol. 2003;10(9):1059–69.

    Article  PubMed  Google Scholar 

  45. Mayo SC, de Jong MC, Pulitano C, Clary BM, Reddy SK, Gamblin TC, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010;17(12):3129–36.

    Article  PubMed  Google Scholar 

  46. Roche A, Girish BV, de Baere T, Baudin E, Boige V, Elias D, et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol. 2003;13(1):136–40.

    PubMed  Google Scholar 

  47. Vogl TJ, Straub R, Eichler K, Sollner O, Mack MG. Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy–local tumor control rate and survival data. Radiology. 2004;230(2):450–8.

    Article  PubMed  Google Scholar 

  48. Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986;315(11):663–6.

    Article  CAS  PubMed  Google Scholar 

  49. di Bartolomeo M, Bajetta E, Buzzoni R, Mariani L, Carnaghi C, Somma L, et al. Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group. Cancer. 1996;77(2):402–8.

    Article  CAS  PubMed  Google Scholar 

  50. Kvols LK, Martin JK, Marsh HM, Moertel CG. Rapid reversal of carcinoid crisis with a somatostatin analogue. N Engl J Med. 1985;313(19):1229–30.

    CAS  PubMed  Google Scholar 

  51. Strosberg J, Kvols L. Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. World J Gastroenterol. 2010;16(24):2963–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Serri O, Brazeau P, Kachra Z, Posner B. Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action. Endocrinology. 1992;130(4):1816–21.

    CAS  PubMed  Google Scholar 

  53. Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27(28):4656–63.

    Article  CAS  PubMed  Google Scholar 

  54. Detjen KM, Welzel M, Farwig K, Brembeck FH, Kaiser A, Riecken EO, et al. Molecular mechanism of interferon alfa-mediated growth inhibition in human neuroendocrine tumor cells. Gastroenterology. 2000;118(4):735–48.

    Article  CAS  PubMed  Google Scholar 

  55. Oberg K, Funa K, Alm G. Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl J Med. 1983;309(3):129–33.

    Article  CAS  PubMed  Google Scholar 

  56. Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46(1):62S–6S.

    CAS  PubMed  Google Scholar 

  57. Bushnell DL, Jr., O’Dorisio TM, O'Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, et al. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28(10):1652–9.

    Article  CAS  PubMed  Google Scholar 

  58. van Essen M, Krenning EP, Kam BL, de Jong M, Valkema R, Kwekkeboom DJ. Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol. 2009;5(7):382–93.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery, University of Miami Miller School of Medicine, Clinical Research Building (C232), 1120 NW 14th Street, 4th Floor, 33136, Miami, FL, USA

    Josefina C. Farra MD

  2. Department of Surgery, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, USA

    Steven E. Rodgers MD, PhD

Authors
  1. Josefina C. Farra MD
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Correspondence to Steven E. Rodgers MD, PhD .

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Editors and Affiliations

  1. Divisions of General Surgery and Surgical Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

    Janice L. Pasieka

  2. Department of Surgery, Columbia University Medical Center, New York, New York, USA

    James A. Lee

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Farra, J., Rodgers, S. (2015). Small Bowel Neuroendocrine Tumors. In: Pasieka, J., Lee, J. (eds) Surgical Endocrinopathies. Springer, Cham. https://doi.org/10.1007/978-3-319-13662-2_53

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  • DOI: https://doi.org/10.1007/978-3-319-13662-2_53

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