Surgical Endoscopy

, Volume 31, Issue 10, pp 3864–3871 | Cite as

Clinical characteristics, risk factors and outcomes of asymptomatic rectal neuroendocrine tumors

  • Sun-Hye Ko
  • Myong Ki BaegEmail author
  • Seung Yeon Ko
  • Hee Sun Jung



Rectal neuroendocrine tumors (NET) are often asymptomatic and frequently discovered during health examinations. However, data on the risk factors of asymptomatic rectal NETs are lacking. We investigated the risk factors, clinical characteristics and outcomes of asymptomatic rectal NETs discovered during health screening.

Materials and methods

Asymptomatic subjects who underwent colonoscopy during routine health screening at a tertiary hospital from March 2009 to July 2014 were reviewed. Subjects with histologically confirmed rectal NETs were compared with healthy controls from the same population. Risk factors for rectal NETs were analyzed by multivariable analysis. Clinical outcomes of the resected NETs were also analyzed.


A total of 21,706 Subjects underwent screening colonoscopy during the study period. 3417 were excluded from the study, and 180 rectal NET subjects were compared with 18,109 controls. Multivariable analysis showed that a previous history of malignancy (OR 2.960, 95% CI 1.673–5.237, p < 0.001), hypertriglyceridemia (OR 1.482, 95% CI 1.046–2.100, p = 0.027), higher fasting plasma glucose levels (OR 1.008, 95% CI 1.003–1.014, p = 0.001) and higher carcinoembryonic antigen levels (OR 1.019, 95% CI 1.003–1.035, p = 0.021) were significant risk factors while older age (OR 0.964, 95% CI 0.951–0.977, p < 0.001) was a preventive factor. One hundred and sixty nine subjects had endoscopic resection, five were treated by local surgery and six by radical surgery. Complete resection was achieved in 152 subjects. There were three cases of positive lymph nodes and one metastasis. Histology revealed four lymphatic, five vascular and two cases of perineural invasion. One hundred and fifty seven subjects were followed up for at least 1 year (median 38.6 months, 12–84 months). There were no recurrences during the follow-up period.


Younger age, previous history of malignancy, higher fasting plasma glucose levels and hypertriglyceridemia are significantly associated with rectal NET risk.


Rectal neuroendocrine tumor Screening colonoscopy Health screening Risk factor Outcome 



This work was supported through the research fund of Catholic Kwandong University, International St. Mary’s Hospital.

Compliance with ethical standards


Drs Sun-Hye Ko, Myong Ki Baeg, Seung Yeon Ko and Hee Sun Jung have no conflicts of interest or financial ties to disclose.


  1. 1.
    Kulke MH, Mayer RJ (1999) Carcinoid tumors. N Engl J Med 340:858–868. doi: 10.1056/nejm199903183401107 CrossRefPubMedGoogle Scholar
  2. 2.
    Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97:934–959. doi: 10.1002/cncr.11105 CrossRefPubMedGoogle Scholar
  3. 3.
    Stewart SL, Wike JM, Kato I, Lewis DR, Michaud F (2006) A population-based study of colorectal cancer histology in the United States, 1998-2001. Cancer 107:1128–1141. doi: 10.1002/cncr.22010 CrossRefPubMedGoogle Scholar
  4. 4.
    Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC (2008) Risk factors associated with neuroendocrine tumors: a US-based case-control study. Int J Cancer 123:867–873. doi: 10.1002/ijc.23529 CrossRefPubMedGoogle Scholar
  5. 5.
    Wang AY, Ahmad NA (2006) Rectal carcinoids. Curr Opin Gastroenterol 22:529–535. doi: 10.1097/01.mog.0000239868.27328.1d CrossRefPubMedGoogle Scholar
  6. 6.
    Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474. doi: 10.1245/s10434-010-0985-4 CrossRefPubMedGoogle Scholar
  7. 7.
    Scherubl H (2009) Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy 41:162–165. doi: 10.1055/s-0028-1119456 CrossRefPubMedGoogle Scholar
  8. 8.
    Jung YS, Yun KE, Chang Y, Ryu S, Park JH, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI, Park DI (2014) Risk factors associated with rectal neuroendocrine tumors: a cross-sectional study. Cancer Epidemiol Biomark Prev 23:1406–1413. doi: 10.1158/1055-9965.epi-14-0132 CrossRefGoogle Scholar
  9. 9.
    Pyo JH, Hong SN, Min BH, Lee JH, Chang DK, Rhee PL, Kim JJ, Choi SK, Jung SH, Son HJ, Kim YH (2016) Evaluation of the risk factors associated with rectal neuroendocrine tumors: a big data analytic study from a health screening center. J Gastroenterol. doi: 10.1007/s00535-016-1198-9 Google Scholar
  10. 10.
    Rindi G, Petrone G, Inzani F (2014) The 2010 WHO classification of digestive neuroendocrine neoplasms: a critical appraisal four years after its introduction. Endocr Pathol 25:186–192. doi: 10.1007/s12022-014-9313-z CrossRefPubMedGoogle Scholar
  11. 11.
    (2015) Standards of medical care in diabetes-2015 abridged for primary care providers. Clin Diabetes 33:97–111. doi: 10.2337/diaclin.33.2.97
  12. 12.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289:2560–2572. doi: 10.1001/jama.289.19.2560 CrossRefPubMedGoogle Scholar
  13. 13.
    National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421Google Scholar
  14. 14.
    McDermott FD, Heeney A, Courtney D, Mohan H, Winter D (2014) Rectal carcinoids: a systematic review. Surg Endosc 28:2020–2026. doi: 10.1007/s00464-014-3430-0 CrossRefPubMedGoogle Scholar
  15. 15.
    Taghavi S, Jayarajan SN, Powers BD, Davey A, Willis AI (2013) Examining rectal carcinoids in the era of screening colonoscopy: a surveillance, epidemiology, and end results analysis. Dis Colon Rectum 56:952–959. doi: 10.1097/DCR.0b013e318291f512 CrossRefPubMedGoogle Scholar
  16. 16.
    Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Seke Etet PF (2013) Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer 20:R1-r17. doi: 10.1530/erc-12-0324 CrossRefPubMedGoogle Scholar
  17. 17.
    Wang H, Chen Y, Fernandez-Del Castillo C, Yilmaz O, Deshpande V (2013) Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway. Mod Pathol 26:139–147. doi: 10.1038/modpathol.2012.143 CrossRefPubMedGoogle Scholar
  18. 18.
    Weinmaster G, Kopan R (2006) A garden of Notch-ly delights. Development 133:3277–3282. doi: 10.1242/dev.02515 CrossRefPubMedGoogle Scholar
  19. 19.
    Jernman J, Kallio P, Hagstrom J, Valimaki MJ, Haapasalo H, Alitalo K, Arola J, Haglund C (2015) PROX1 is involved in progression of rectal neuroendocrine tumors, NETs. Virchows Arch 467:279–284. doi: 10.1007/s00428-015-1795-7 CrossRefPubMedGoogle Scholar
  20. 20.
    Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Magi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparso T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proenca C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O’Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben-Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Bottcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jorgensen T, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Lyssenko V, Mahley R, Mangino M, Manning AK, Martinez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orru M, Pakyz R, Palmer CN, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvanen AC, Tanaka T, Thorand B, Tichet J, Tonjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Rios M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP, Wichmann HE, Illig T, Rudan I, Wright AF, Stumvoll M, Campbell H, Wilson JF, Bergman RN, Buchanan TA, Collins FS, Mohlke KL, Tuomilehto J, Valle TT, Altshuler D, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Frayling TM, Ferrucci L, Kong A, Thorsteinsdottir U, Stefansson K, van Duijn CM, Aulchenko YS, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Abecasis GR, Wareham NJ, Sladek R, Froguel P, Watanabe RM, Meigs JB, Groop L, Boehnke M, McCarthy MI, Florez JC, Barroso I (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105–116. doi: 10.1038/ng.520 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Toumpanakis CG, Caplin ME (2008) Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Am J Gastroenterol 103:729–732. doi: 10.1111/j.1572-0241.2007.01777.x CrossRefPubMedGoogle Scholar
  22. 22.
    Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC (2008) Family history of cancer and associated risk of developing neuroendocrine tumors: a case-control study. Cancer Epidemiol Biomark Prev 17:959–965. doi: 10.1158/1055-9965.epi-07-0750 CrossRefGoogle Scholar
  23. 23.
    Corkum M, Hayden JA, Kephart G, Urquhart R, Schlievert C, Porter G (2013) Screening for new primary cancers in cancer survivors compared to non-cancer controls: a systematic review and meta-analysis. J Cancer Surviv 7:455–463. doi: 10.1007/s11764-013-0278-6 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chi Y, Du F, Zhao H, Wang JW, Cai JQ (2014) Characteristics and long-term prognosis of patients with rectal neuroendocrine tumors. World J Gastroenterol 20:16252–16257. doi: 10.3748/wjg.v20.i43.16252 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  2. 2.Division of Gastroenterology, Department of Internal Medicine, International St. Mary’s Hospital, College of MedicineCatholic Kwandong UniversitySeo-guSouth Korea
  3. 3.Department of Surgery, Incheon St. Mary’s Hospital, College of MedicineCatholic University of KoreaIncheonSouth Korea
  4. 4.Department of Health Promotion, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeoulSouth Korea

Personalised recommendations