Neuroendocrine, goblet cell and mixed adeno-neuroendocrine tumours of the appendix: updates, clinical applications and the future

Expert Review of Gastroenterology and Hepatology

Volumn 11, Issue 3, 2017, Pages 237-247

  Clift, Ashley K ^a   Frilling, Andrea ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Appendix; carcinoma; goblet cell; mixed adeno neuroendocrine; neoplasm; neuroendocrine; surgery

Indexed keywords

COPPER 64; GALLIUM 68;

APPENDECTOMY; APPENDICEAL NEUROENDOCRINE TUMOR; CANCER GRADING; CANCER STAGING; CANCER SURVIVAL; CARCINOMA; CLINICAL EFFECTIVENESS; CYTOREDUCTIVE SURGERY; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR; GENE EXPRESSION PROFILING; GOBLET CELL; GOBLET CELL CARCINOMA; HEMICOLECTOMY; HUMAN; HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; LIVER METASTASIS; LYMPH NODE METASTASIS; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY; REVIEW; SURVIVAL RATE; TREATMENT OUTCOME; TUMOR VOLUME; X-RAY COMPUTED TOMOGRAPHY; ADENOCARCINOMA; ALGORITHM; APPENDICEAL NEOPLASMS; CLASSIFICATION; CLINICAL DECISION MAKING; CLINICAL PATHWAY; DECISION SUPPORT SYSTEM; NEOPLASMS, COMPLEX AND MIXED; NEUROENDOCRINE TUMORS; PATHOLOGY; PATIENT SELECTION; PREDICTIVE VALUE; TIME FACTOR;

ADENOCARCINOMA; ALGORITHMS; APPENDICEAL NEOPLASMS; CLINICAL DECISION-MAKING; CRITICAL PATHWAYS; DECISION SUPPORT TECHNIQUES; GOBLET CELLS; HUMANS; NEOPLASMS, COMPLEX AND MIXED; NEUROENDOCRINE TUMORS; PATIENT SELECTION; PREDICTIVE VALUE OF TESTS; TIME FACTORS; TREATMENT OUTCOME;

EID: 85012013972     PISSN: 17474124     EISSN: 17474132     Source Type: Journal    
DOI: 10.1080/17474124.2017.1282314     Document Type: Review

References (90)

1. Ellis L, Shale MJ, Coleman MP., Carcinoid tumors of the gastrointestinal tract:trends in incidence in England since 1971. Am J Gastroenterol. 2010 Dec;105:2563–2569.
2. Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor epidemiology:contrasting Norway and North America. Cancer. 2008 Nov 15;113:2655–2664.
3. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97:934–959.
4. Lawrence B, Gustafsson BI, Chan A, et al. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011 Mar;40:1–18, vii.
5. Yao JC, Hassan M, Phan A, 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 Jun 20;26:3063–3072.
6. Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, et al. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs):results from the National Cancer Registry of Spain (RGETNE). Ann Oncol. 2010;21:1794–1803.
7. Pape U-F, Niederle B, Costa F, et al. ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas). Neuroendocrinology. 2016;103:144–152.•• This article sets out the current optimal standards for the management of patients with appendiceal neuroendocrine tumors.
8. Moertel CG, Dockerty MB, Judd ES. Carcinoid tumors of the vermiform appendix. Cancer. 1968 Feb;21:270–278.
9. Tchana-Sato V, Detry O, Polus M, et al. Carcinoid tumor of the appendix:a consecutive series from 1237 appendectomies. World J Gastroenterol. 2006 Nov 7;12:6699–6701.
10. Debnath D, Rees J, Myint F. Are we missing diagnostic opportunities in cases of carcinoid tumours of the appendix? Surgeon. 2008 Oct;6:266–272.
11. Doede T, Foss HD, Waldschmidt J. Carcinoid tumors of the appendix in children–epidemiology, clinical aspects and procedure. Eur J Pediatr Surg. 2000 Dec;10:372–377.
12. van Gompel JJ, Stoddard E, Chen H. Incidental carcinoid tumors of the appendix:do they affect presentation or prognosis?. Int Surg. 2007;92:331–334.
13. Amr B, Froghi F, Edmond M, et al. Management and outcomes of appendicular neuroendocrine tumours:retrospective review with 5-year follow-up. Eur J Surg Oncol. 2015 Sep;41:1243–1246.
14. Landry CS, Woodall C, Scoggins CR, et al. Analysis of 900 appendiceal carcinoid tumors for a proposed predictive staging system. Arch Surg. 2008 Jul;143:664–670.
15. Mullen JT, Savarese DMF. Carcinoid tumors of the appendix:a population-based study. J Surg Oncol. 2011 Jul 1;104:41–44.• This study demonstrates and quantifies the ability of appendiceal neuroendocrine tumors to exhibit metastasis.
16. Pape U-F, Perren A, Niederle B, et al. ENETS consensus guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology. 2012;95:135–156.
17. Alexandraki KI, Kaltsas GA, Grozinsky-Glasberg S, et al. Appendiceal neuroendocrine neoplasms:diagnosis and management. Endocr Relat Cancer. 2016 Jan;23:R27–41.
18. Clift AK, Faiz O, Al-Nahhas A, et al. Role of staging in patients with small intestinal neuroendocrine tumours. J Gastrointest Surg. 2016;20:180–8; discussion 188.
19. Norlén O, Stålberg P, Öberg K, et al. Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg. 2012;36:1419–1431.
20. Han X, Zhang C, Tang M, et al. The value of serum chromogranin A as a predictor of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors with liver metastases. Eur J Gastroenterol Hepatol. 2015;27:527–535.
21. Kidd M, Bodei L, Modlin IM, et al. any relevance in neuroendocrine tumors? Curr Opin Endocrinol Diabetes Obes. 2016 Feb;23:28–37.
22. Ardill JE, Armstrong L, Smye M, et al. Neuroendocrine tumours of the small bowel:- interpretation of raised circulating chromogranin A, urinary 5 hydroxy indole acetic acid and neurokinin A. Qjm. 2015 May 15. DOI:10.1093/qjmed/hcv095
23. de Herder WW. Biochemistry of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007 Mar;21:33–41.
24. Alexandraki KI, Griniatsos J, Bramis KI, et al. Clinical value of right hemicolectomy for appendiceal carcinoids using pathologic criteria. J Endocrinol Invest. 2011;34:255–259.
25. Prommegger R, Ensinger C, Adlassnig C, et al. Catestatin–a novel neuropeptide in carcinoid tumors of the appendix. Anticancer Res. 2004;24:311–316.
26. Modlin IM, Kidd M, Latich I, et al. Genetic differentiation of appendiceal tumor malignancy:a guide for the perplexed. Ann Surg. 2006 Jul;244:52–60.•• This report was the first to use ‘modern’ molecular methods to distinguish between appendiceal neoplasms.
27. Sundin A, Vullierme M-P, Kaltsas G, et al. Mallorca consensus conference participants, European Neuroendocrine Tumor Society:ENETS consensus guidelines for the standards of care in neuroendocrine tumors:radiological examinations. Neuroendocrinology. 2009;90:167–183.
28. Coursey CA, Nelson RC, Moreno RD, et al. Carcinoid tumors of the appendix:are these tumors identifiable prospectively on preoperative CT? Am Surg. 2010 Mar;76:273–275.
29. Kwekkeboom DJ, Krenning EP, Scheidhauer K, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors:somatostatin receptor imaging with (111)in-pentetreotide. Neuroendocrinology. 2009;90:184–189.
30. Frilling A, Sotiropoulos GC, Radtke A, et al. The impact of 68Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors. Ann Surg. 2010;252:850–856.
31. Pfeifer A, Knigge U, Mortensen J, et al. Clinical PET of neuroendocrine tumors using 64Cu-DOTATATE:first-in-humans study. J Nucl Med. 2012;53:1207–1215.
32. Rindi G, Klöppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors:a consensus proposal including a grading system. Virchows Arch. 2007;451:757–762.
33. Sobin LH, Gospodarowicz MK, Mary K, et al. International union against cancer.:TNM classification of malignant tumours. Chichester (UK):Wiley-Blackwell; 2009.
34. Oberg K, Modlin IM, de Herder W, et al. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015;16:e435–46.
35. Modlin IM, Frilling A, Salem RR, et al. Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2015 Oct 5. DOI:10.1016/j.surg.2015.06.056
36. Ćwikła JB, Bodei L, Kolasinska-Ćwikła A, et al. Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy. J Clin Endocrinol Metab. 2015 Nov;100:E1437–45.
37. Pape U-F, Niederle B, Costa F, et al. ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas). Neuroendocrinology. 2016;103:144–152.
38. Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012;61:6–32.
39. Goede AC, Caplin ME, Winslet MC. Carcinoid tumour of the appendix. Br J Surg. 2003 Nov;90:1317–1322.
40. Moertel CG, Weiland LH, Nagorney DM, et al. Carcinoid tumor of the appendix:treatment and prognosis. N Engl J Med. 1987 Dec 31;317:1699–1701.
41. Bamboat ZM, Berger DL. Is right hemicolectomy for 2.0-cm appendiceal carcinoids justified? Arch Surg. 2006 Apr;141:349–352.
42. Moertel CG, Sauer WG, Dockerty MB, et al. Life history of the carcinoid tumor of the small intestine. Cancer. 1961 Jan;14:901–912.
43. Groth SS, Virnig BA, Al-Refaie WB, et al. Appendiceal carcinoid tumors:predictors of lymph node metastasis and the impact of right hemicolectomy on survival. J Surg Oncol. 2011 Jan 1;103:39–45.
44. Stinner B, Kisker O, Zielke A, et al. Surgical management for carcinoid tumors of small bowel, appendix, colon, and rectum. World J Surg. 1996 Feb;20:183–188.
45. Stinner B, Rothmund M. Neuroendocrine tumours (carcinoids) of the appendix. Best Pract Res Clin Gastroenterol. 2005 Oct;19:729–738.
46. Grozinsky-Glasberg S, Alexandraki KI, Barak D, et al. Current size criteria for the management of neuroendocrine tumors of the appendix:are they valid? Clinical experience and review of the literature. Neuroendocrinology. 2013 Jan;98:31–37.• An important critical analysis of the clinical ramifications of following ENETS consensus guidelines in the management of patients with appendiceal neuroendocrine tumors.
47. Kleiman DA, Finnerty B, Beninato T, et al. Features associated with metastases among well-differentiated neuroendocrine (carcinoid) tumors of the appendix:the significance of small vessel invasion in addition to size. Dis Colon Rectum. 2015;58:1137–1143.
48. Syracuse DC, Perzin KH, Price JB, et al. Carcinoid tumors of the appendix. Mesoappendiceal extension and nodal metastases. Ann Surg. 1979 Jul;190:58–63.
49. Roggo A, Wood WC, Ottinger LW. Carcinoid tumors of the appendix. Ann Surg. 1993 Apr;217:385–390.
50. Liu E, Telem DA, Hwang J, et al. The clinical utility of Ki-67 in assessing tumor biology and aggressiveness in patients with appendiceal carcinoids. J Surg Oncol. 2010 Sep 15;102:338–341.
51. De Lambert G, Lardy H, Martelli H, et al. Surgical management of neuroendocrine tumors of the appendix in children and adolescents:a retrospective french multicenter study of 114 cases. Pediatr Blood Cancer. 2016 Apr;63:598–603.
52. Ciarrocchi A, Pietroletti R, Carlei F, et al. Propensity adjusted appraisal of the surgical strategy for appendiceal carcinoids. Tech Coloproctol. 2015 Jan;19:35–41.
53. Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer. 2015 Apr 15;121:1172–1186.
54. Frilling A, Li J, Malamutmann E, et al. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease. Br J Surg. 2009 Feb;96:175–184.
55. Murray SE, R V L, Sippel RS, et al. Postoperative surveillance of small appendiceal carcinoid tumors. Am J Surg. 2014 Mar;207:342–345.
56. Subbuswamy SG, Gibbs NM, Ross CF, et al. Goblet cell carcinoid of the appendix. Cancer. 1974 Aug;34:338–344.
57. Klein HZ. Mucinous carcinoid tumor of the vermiform appendix. Cancer. 1974 Mar;33:770–777.
58. Warkel RL, Cooper PH, Helwig EB. Adenocarcinoid, a mucin-producing carcinoid tumor of the appendix:a study of 39 cases. Cancer. 1978 Dec;42:2781–2793.
59. Holt N, Grønbæk H. Goblet cell carcinoids of the appendix. ScientificWorldJournal. 2013;2013:1–6.
60. Roy P, Chetty R. Goblet cell carcinoid tumors of the appendix:an overview. World J Gastrointest Oncol. 2010 Jun 15;2:251–258.
61. McCusker ME, Coté TR, Clegg LX, et al. Primary malignant neoplasms of the appendix:a population-based study from the surveillance, epidemiology and end-results program, 1973-1998. Cancer. 2002 Jun 15;94:3307–3312.
62. Pham TH, Wolff B, Abraham SC, et al. Surgical and chemotherapy treatment outcomes of goblet cell carcinoid:a tertiary cancer center experience. Ann Surg Oncol. 2006 Mar;13:370–376.
63. Stancu M, Wu -T-T, Wallace C, et al. Genetic alterations in goblet cell carcinoids of the vermiform appendix and comparison with gastrointestinal carcinoid tumors. Mod Pathol. 2003 Dec 1;16:1189–1198.
64. Ramnani DM, Wistuba II, Behrens C, et al. K-ras and p53 mutations in the pathogenesis of classical and goblet cell carcinoids of the appendix. Cancer. 1999 Jul 1;86:14–21.
65. van Eeden S, Offerhaus GJA, Hart AAM, et al. Goblet cell carcinoid of the appendix:a specific type of carcinoma. Histopathology. 2007;51:763–773.
66. Jiang Y, Long H, Wang W, et al. Clinicopathological features and immunoexpression profiles of goblet cell carcinoid and typical carcinoid of the appendix. Pathol Oncol Res. 2011 Mar 18;17:127–132.
67. Toumpanakis C, Standish RA, Baishnab E, et al. Goblet cell carcinoid tumors (adenocarcinoid) of the appendix. Dis Colon Rectum. 2007 Mar;50:315–322.
68. Ng D, Falck V, McConnell YJ, et al. Appendiceal goblet cell carcinoid and mucinous neoplasms are closely associated tumors:lessons from their coexistence in primary tumors and concurrence in peritoneal dissemination. J Surg Oncol. 2014 May;109:548–555.
69. Tang LH, Shia J, Soslow RA, et al. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol. 2008;32:1429–1443.
70. Lamarca A, Nonaka D, Lopez Escola C, et al. Appendiceal goblet cell carcinoids:management considerations from a reference peritoneal tumour service centre and ENETS centre of excellence. Neuroendocrinology. 2016;103:500–517.• This report details important experience with a large cohort of goblet cell cancers at a specialist center.
71. Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors. Pancreas. 2010;39:753–766.
72. Varisco B, McAlvin B, Dias J, et al. Adenocarcinoid of the appendix:is right hemicolectomy necessary? A meta-analysis of retrospective chart reviews. Am Surg. 2004 Jul;70:593–599.
73. Bucher P, Gervaz P, Ris F, et al. Surgical treatment of appendiceal adenocarcinoid (goblet cell carcinoid). World J Surg. 2005 Nov;29:1436–1439.
74. Byrn JC, Wang J-L, Divino CM, et al. Management of goblet cell carcinoid. J Surg Oncol. 2006 Oct 1;94:396–402.
75. Rossi RE, Luong T-V, Caplin ME, et al. Goblet cell appendiceal tumors–management dilemmas and long-term outcomes. Surg Oncol. 2015;24:47–53.
76. McConnell YJ, Mack LA, Gui X, et al. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy:an emerging treatment option for advanced goblet cell tumors of the appendix. Ann Surg Oncol. 2014 Jun 8;21:1975–1982.
77. Cashin P, Nygren P, Hellman P, et al. Appendiceal adenocarcinoids with peritoneal carcinomatosis treated with cytoreductive surgery and intraperitoneal chemotherapy:a retrospective study of in vitro drug sensitivity and survival. Clin Colorectal Cancer. 2011 Jun;10:108–112.
78. Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. Lyon:International Agency for Research on Cancer. 2010.
79. Gagné F, Fortin P, Dufour V, et al. [Tumors of the appendix associating histologic features of carcinoid and adenocarcinoma]. Ann Anat Pathol (Paris). 1969;14:393–406.
80. La Rosa S, Marando A, Sessa F, et al. Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract:an update. Cancers (Basel). 2012 Jan 16;4:11–30.
81. Capella C, La Rosa S, Uccella S, et al. Mixed endocrine-exocrine tumors of the gastrointestinal tract. Semin Diagn Pathol. 2000 May;17:91–103.
82. Brathwaite S, Rock J, Yearsley MM, et al. Mixed adeno-neuroendocrine carcinoma:an aggressive clinical entity. Ann Surg Oncol. 2016;23:2281–2286.
83. Brathwaite S, Yearsley MM, Bekaii-Saab T, et al. Appendiceal mixed adeno-neuroendocrine carcinoma:a population-based study of the surveillance, epidemiology, and end results registry. Front Oncol. 2016;6:148.
84. Boyar Cetinkaya R, Aagnes B, Thiis-Evensen E, et al. Trends in incidence of neuroendocrine neoplasms in Norway:a report of 16,075 cases from 1993 through 2010. Neuroendocrinology. 2015 Nov 13. DOI:10.1159/000442207
85. Rinke A, Wittenberg M, Schade-Brittinger C, 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 (PROMID):results on long term survival. Neuroendocrinology. 2016 Jan 6. DOI:10.1159/000443612
86. Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4):a randomised, placebo-controlled, phase 3 study. Lancet (London, England). 2016 Mar 5;387:968–977.
87. Modlin IM, Oberg K, Taylor A, et al. Neuroendocrine tumor biomarkers:current status and perspectives. Neuroendocrinology. 2014 Jan;100:265–277.
88. Oberg K, Krenning E, Sundin A, et al. A Delphic consensus assessment:imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management. Endocr Connect. 2016;5:174–187.
89. Vélayoudom-Céphise F-L, Duvillard P, Foucan L, et al. Are G3 ENETS neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer. 2013;20:649–657.
90. Öberg K. Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence-based medicine - A scandinavian view. Scand J Gastroenterol. 2015 Jun;50:727–739.