Skip to main content

Advertisement

SpringerLink
Log in

Excellent prognosis following endoscopic resection of patients with rectal neuroendocrine tumors despite the frequent presence of lymphovascular invasion

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Endoscopic resection (ER) has been increasingly used for the treatment of rectal neuroendocrine tumors (NETs); however, only limited data are available on its long-term outcomes. This study analyzed the long-term outcomes of rectal NETs treated by ER and characterized potential risk factors for metastasis in these cases, with emphasis on lymphovascular invasion.

Methods

We retrospectively analyzed the clinicopathological features and outcomes of 86 patients with 90 rectal NETs who had been treated by ER. Lymphovascular invasion was reevaluated using elastic-staining and double-staining immunohistochemistry.

Results

En bloc resection with tumor-free margins was achieved in 87 lesions (96.7 %). The median tumor size was 5 mm (range 2–13), and all the lesions were confined to the submucosal layer. The Ki-67 index was less than 3 % in all the lesions, which were therefore classified as NET G1. Elastic-staining and double-staining immunohistochemistry revealed the presence of lymphatic and venous invasion in 23 (25.6 %) and 35 lesions (36.7 %), respectively. Collectively, lymphatic and/or vascular invasion was identified in 42 lesions (46.7 %). All cases were followed up without additional surgery, and no metastasis or recurrence was detected during the median follow-up period of 67.5 months.

Conclusions

This study showed an excellent long-term prognosis following ER of patients with rectal NETs, confirming that ER is a valid treatment option for small rectal NETs. The present study also revealed highly prevalent lymphovascular invasion even in minute rectal NETs; this observation raises a question regarding its significance as a risk factor for metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Klimstra DS, Anold R, Capella C, et al. Neuroendocrine neoplasms of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, et al., editors. WHO classification of tumors of the digestive system. 4th ed. Lyon: IARC; 2010. p. 174–7.

    Google Scholar 

  2. Anthony LB, Strosberg JR, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (nets): well-differentiated nets of the distal colon and rectum. Pancreas. 2010;39:767–74.

    Article  PubMed  Google Scholar 

  3. Caplin M, Sundin A, Nillson O, et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology. 2012;95:88–97.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  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;26:3063–72.

    Article  PubMed  Google Scholar 

  6. Scherübl H. Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy. 2009;41:162–5.

    Article  PubMed  Google Scholar 

  7. Ito T, Igarashi H, Nakamura K, et al. Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis. J Gastroenterol 2014 (Epub ahead of print).

  8. Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005;103:1587–95.

    Article  PubMed  Google Scholar 

  9. Konishi T, Watanabe T, Kishimoto J, et al. Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut. 2007;56:863–8.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Fahy BN, Tang LH, Klimstra D, et al. Carcinoid of the rectum risk stratification (CaRRs): a strategy for preoperative outcome assessment. Ann Surg Oncol. 2007;14:1735–43.

    Article  PubMed  Google Scholar 

  11. Shields CJ, Tiret E, Winter DC. Carcinoid tumors of the rectum: a multi-institutional international collaboration. Ann Surg. 2010;252:750–5.

    Article  PubMed  Google Scholar 

  12. Fujimoto Y, Oya M, Kuroyanagi H, et al. Lymph-node metastases in rectal carcinoids. Langenbecks Arch Surg. 2010;395:139–42.

    Article  PubMed  Google Scholar 

  13. Park CH, Cheon JH, Kim JO, et al. Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread. Endoscopy. 2011;43:790–5.

    Article  CAS  PubMed  Google Scholar 

  14. Kasuga A, Chino A, Uragami N, et al. Treatment strategy for rectal carcinoids: a clinicopathological analysis of 229 cases at a single cancer institution. J Gastroenterol Hepatol. 2012;27:1801–7.

    Article  PubMed  Google Scholar 

  15. Tomoda H, Furusawa M, Hayashi I, et al. A rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis: a case report and a review of the literature. Jpn J Surg. 1990;20:468–71.

    Article  CAS  PubMed  Google Scholar 

  16. Shinohara T, Hotta K, Oyama T. Rectal carcinoid tumor, 6 mm in diameter, with lymph node metastases. Endoscopy. 2008;40(Suppl 2):E40–1.

    Article  PubMed  Google Scholar 

  17. Yamagishi D, Matsubara N, Noda M, et al. Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection. Oncol Lett. 2012;4:910–4.

    PubMed Central  PubMed  Google Scholar 

  18. Kawahara M, Kammori M, Kanauchi H, et al. Immunohistochemical prognostic indicators of gastrointestinal carcinoid tumours. Eur J Surg Oncol. 2002;28:140–6.

    Article  CAS  PubMed  Google Scholar 

  19. Hotta K, Shimoda T, Nakanishi Y, et al. Usefulness of Ki-67 for predicting the metastatic potential of rectal carcinoids. Pathol Int. 2006;56:591–6.

    Article  PubMed  Google Scholar 

  20. Yoon SN, Yu CS, Shin US, et al. Clinicopathological characteristics of rectal carcinoids. Int J Colorectal Dis. 2010;25:1087–92.

    Article  PubMed  Google Scholar 

  21. Shim KN, Yang SK, Myung SJ, et al. Atypical endoscopic features of rectal carcinoids. Endoscopy. 2004;36:313–6.

    Article  PubMed  Google Scholar 

  22. Kim BN, Sohn DK, Hong CW, et al. Atypical endoscopic features can be associated with metastasis in rectal carcinoid tumors. Surg Endosc. 2008;22:1992–6.

    Article  PubMed  Google Scholar 

  23. Lee DS, Jeon SW, Park SY, et al. The feasibility of endoscopic submucosal dissection for rectal carcinoid tumors: comparison with endoscopic mucosal resection. Endoscopy. 2010;42:647–51.

    Article  CAS  PubMed  Google Scholar 

  24. Kim HH, Park SJ, Lee SH, et al. Efficacy of endoscopic submucosal resection with a ligation device for removing small rectal carcinoid tumor compared with endoscopic mucosal resection: analysis of 100 cases. Dig Endosc. 2012;24:159–63.

    Article  PubMed  Google Scholar 

  25. Suzuki S, Ishii N, Uemura M, et al. Endoscopic submucosal dissection (ESD) for gastrointestinal carcinoid tumors. Surg Endosc. 2012;26:759–63.

    Article  PubMed  Google Scholar 

  26. Kim KM, Eo SJ, Shim SG, et al. Treatment outcomes according to endoscopic treatment modalities for rectal carcinoid tumors. Clin Res Hepatol Gastroenterol. 2013;37:275–82.

    Article  PubMed  Google Scholar 

  27. Kim GU, Kim KJ, Hong SM, et al. Clinical outcomes of rectal neuroendocrine tumors ≤10 mm following endoscopic resection. Endoscopy. 2013;45:1018–23.

    Article  PubMed  Google Scholar 

  28. Shigeta K, Okabayashi K, Hasegawa H, et al. Long-term outcome of patients with locally resected high- and low-risk rectal carcinoid tumors. J Gastrointest Surg. 2014;18:768–73.

    Article  PubMed  Google Scholar 

  29. Fogt F, Zimmerman RL, Ross HM, et al. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep. 2004;11:47–50.

    CAS  PubMed  Google Scholar 

  30. Inoue T, Mori M, Shimono R, et al. Vascular invasion of colorectal carcinoma readily visible with certain stains. Dis Colon Rectum. 1992;35:34–9.

    Article  CAS  PubMed  Google Scholar 

  31. Vass DG, Ainsworth R, Anderson JH, et al. The value of an elastic tissue stain in detecting venous invasion in colorectal cancer. J Clin Pathol. 2004;57:769–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Edge SB, Byrd DR, Compton CC, et al., editors. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  33. Sekine S, Ogawa R, Kanai Y. Hepatomas with activating Ctnnb1 mutations in ‘Ctnnb1-deficient’ livers: a tricky aspect of a conditional knockout mouse model. Carcinogenesis. 2011;32:622–8.

    Article  CAS  PubMed  Google Scholar 

  34. Wiedenmann B. Kahn HJ, Marks A. Synaptophysin. A widespread constituent of small neuroendocrine vesicles and a new tool in tumor diagnosis. Acta Oncol. 1991;30:435–40.

    Article  CAS  PubMed  Google Scholar 

  35. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest 2002; 82:1255-1257.

  36. Fukunaga M. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology. 2005;46:396–402.

    Article  CAS  PubMed  Google Scholar 

  37. Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem. 2006;54:385–95.

    Article  CAS  PubMed  Google Scholar 

  38. de Mestier L, Brixi H, Gincul R, et al. Updating the management of patients with rectal neuroendocrine tumors. Endoscopy. 2013;45:1039–46.

    Article  PubMed  Google Scholar 

  39. Ono A, Fujii T, Saito Y, et al. Endoscopic submucosal resection of rectal carcinoid tumors with a ligation device. Gastrointest Endosc. 2003;57:583–7.

    Article  PubMed  Google Scholar 

  40. Mashimo Y, Matsuda T, Uraoka T, et al. Endoscopic submucosal resection with a ligation device is an effective and safe treatment for carcinoid tumors in the lower rectum. J Gastroenterol Hepatol. 2008;23:218–21.

    Article  PubMed  Google Scholar 

  41. Saito Y, Yamada M, So E, et al. Colorectal endoscopic submucosal dissection: technical advantages compared to endoscopic mucosal resection and minimally invasive surgery. Dig Endosc. 2014;26(Suppl 1):52–61.

    Article  PubMed  Google Scholar 

  42. Kwaan MR, Goldberg JE, Bleday R. Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg. 2008;143:471–5.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Sachiko Miura for the skillful technical assistance. This work was supported by the National Cancer Center Research and Development Fund (23-A-11).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan

    Masau Sekiguchi, Taku Sakamoto, Yosuke Otake, Takeshi Nakajima, Takahisa Matsuda & Yutaka Saito

  2. Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Masau Sekiguchi & Yuichiro Ohe

  3. Pathology and Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Shigeki Sekine, Hirokazu Taniguchi & Ryoji Kushima

Authors
  1. Masau Sekiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shigeki Sekine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taku Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yosuke Otake
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takeshi Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahisa Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hirokazu Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ryoji Kushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuichiro Ohe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yutaka Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shigeki Sekine.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sekiguchi, M., Sekine, S., Sakamoto, T. et al. Excellent prognosis following endoscopic resection of patients with rectal neuroendocrine tumors despite the frequent presence of lymphovascular invasion. J Gastroenterol 50, 1184–1189 (2015). https://doi.org/10.1007/s00535-015-1079-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-015-1079-7

Keywords

Search

Navigation