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Inspection of Perirectal Lymph Nodes by One-Step Nucleic Acid Amplification Predicts Lateral Lymph Node Metastasis in Advanced Rectal Cancer

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Lateral lymph node dissection (LLND) is performed for advanced rectal cancers in Japan; however, it can cause sexual and urinary dysfunction. The incidence of lateral LN metastasis is estimated at 7–13.9%; therefore, excessive rectal surgery with LLND should be avoided, especially for prophylactic purposes. To identify the patients who require LLND, we examined metastases in perirectal LNs by using a one-step nucleic acid amplification (OSNA) assay to predict lateral LN metastases.

Methods

Twenty-five patients who underwent surgery with bilateral LN dissection due to T3–T4 rectal cancers were prospectively included in this study. Twenty-two patients (88.0%) received preoperative chemotherapy. Among 1052 LNs from 25 patients (median 40 per case), 135 perirectal LNs (median 6 per patient) were divided into three pieces and analyzed by OSNA, reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen mRNA, and pathological examination after surgery. These results were compared with the pathological diagnosis of lateral LNs.

Results

Lateral LN metastases were present in 4 of 25 patients (16.0%). All of these patients were positive by OSNA for perirectal LN metastases. The OSNA assay had a sensitivity of 100%, specificity of 86%, positive predictive value of 57%, and negative predictive value (NPV) of 100% for predicting lateral LN metastases.

Conclusions

The findings from this prospective study suggest that the OSNA assay of perirectal LNs may be useful for determining when LLND is necessary because of its high NPV, even in patients treated with preoperative chemotherapy.

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REFERENCES

  1. Blair JB, Holyoke EA, Best RR. A note on the lymphatics of the middle and lower rectum and anus. Anat Rec. 1950;108(4):635–44.

    Article  CAS  PubMed  Google Scholar 

  2. Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.

    Article  CAS  PubMed  Google Scholar 

  3. Enker WE. Potency, cure, and local control in the operative treatment of rectal cancer. Arch Surg. 1992;127(12):1396–401.

    Article  CAS  PubMed  Google Scholar 

  4. Murty M, Enker WE, Martz J. Current status of total mesorectal excision and autonomic nerve preservation in rectal cancer. Semin Surg Oncol. 2000;19(4):321–8.

    Article  CAS  PubMed  Google Scholar 

  5. Pocard M, Zinzindohoue F, Haab F, Caplin S, Parc R, Tiret E. A prospective study of sexual and urinary function before and after total mesorectal excision with autonomic nerve preservation for rectal cancer. Surgery. 2002;131(4):368–72.

    Article  PubMed  Google Scholar 

  6. Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish rectal cancer trial: Long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23(24):5644–50.

    Article  PubMed  Google Scholar 

  7. Peeters KCMJ, Marijnen CAM, Nagtegaal ID, et al. The TME trial after a median follow-up of 6 years. Ann Surg. 2007;246(5):693–701.

    Article  PubMed  Google Scholar 

  8. Temple LKF, Wong WD, Minsky B. The impact of radiation on functional outcomes in patients with rectal cancer and sphincter preservation. Semin Radiat Oncol. 2003;13(4):469–77.

    Article  PubMed  Google Scholar 

  9. Bruheim K, Guren MG, Skovlund E, et al. Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2010;76(4):1005–11.

    Article  PubMed  Google Scholar 

  10. Ishii Y, Hasegawa H, Endo T, et al. Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Oncol. 2010;36(11):1061–5.

    Article  CAS  PubMed  Google Scholar 

  11. Uehara K, Hiramatsu K, Maeda A, et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 phase II trial. Jpn J Clin Oncol. 2013;43(10):964–71.

    Article  PubMed  Google Scholar 

  12. Hasegawa J, Nishimura J, Mizushima T, et al. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol. 2014;73(5):1079–87.

    Article  CAS  PubMed  Google Scholar 

  13. Kamiya T, Uehara K, Nakayama G, et al. Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study. Eur J Surg Oncol. 2016;42(6):829–35.

    Article  CAS  PubMed  Google Scholar 

  14. Uehara K, Nagino M. Neoadjuvant treatment for locally advanced rectal cancer: a systematic review. Surg Today. 2016;46(2):161–8.

    Article  CAS  PubMed  Google Scholar 

  15. Schrag D, Weiser MR, Goodman KA, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32(6):513–8.

    Article  CAS  PubMed  Google Scholar 

  16. Glynne-Jones R, Hava N, Goh V, et al. Bevacizumab and combination chemotherapy in rectal cancer until surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum. BMC Cancer. 2015;15:764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yokoyama S, Takifuji K, Hotta T, et al. Survival benefit of lateral lymph node dissection according to the region of involvement and the number of lateral lymph nodes involved. Surg Today. 2014;44(6):1097–103.

    Article  PubMed  Google Scholar 

  18. Watanabe T, Itabashi M, Shimada Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2014 for treatment of colorectal cancer. Int J Clin Oncol. 2015;20(2):207–39.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nagawa H, Muto T, Sunouchi K, et al. Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy. Dis Colon Rectum. 2001;44(9):1274–80.

    Article  CAS  PubMed  Google Scholar 

  20. Kyo K, Sameshima S, Takahashi M, Furugori T, Sawada T. Impact of autonomic nerve preservation and lateral node dissection on male urogenital function after total mesorectal excision for lower rectal cancer. World J Surg. 2006;30(6):1014–9.

    Article  PubMed  Google Scholar 

  21. Çöl C, Hasdemir O, Yalcin E, et al. The assessment of urinary function following extended lymph node dissection for colorectal cancer. Eur J Surg Oncol. 2005;31(3):237–41.

    Article  PubMed  Google Scholar 

  22. Matsuoka H, Masaki T, Sugiyama M, Atomi Y. Impact of lateral pelvic lymph node dissection on evacuatory and urinary functions following low anterior resection for advanced rectal carcinoma. Langenbeck’s Arch Surg. 2005;390(6):517–22.

    Article  Google Scholar 

  23. Georgiou P, Tan E, Gouvas N, et al. Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis. Lancet Oncol. 2009;10(11):1053–62.

    Article  PubMed  Google Scholar 

  24. Fujita S, Akasu T, Mizusawa J, et al. Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): Results from a multicentre, randomised controlled, non-inferiority trial. Lancet Oncol. 2012;13(6):616–21.

    Article  PubMed  Google Scholar 

  25. Fujita S, Yamamoto S, Akasu T, Moriya Y. Risk factors of lateral pelvic lymph node metastasis in advanced rectal cancer. Int J Colorectal Dis. 2009;24:1085–90.

    Article  PubMed  Google Scholar 

  26. Tan KY, Yamamoto S, Fujita S, Akasu T, Moriya Y. Improving prediction of lateral node spread in low rectal cancers: multivariate analysis of clinicopathological factors in 1,046 cases. Langenbeck’s Arch Surg. 2010;395(5):545–9.

    Article  Google Scholar 

  27. Akiyoshi T, Watanabe T, Miyata S, Kotake K, Muto T, Sugihara K. Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease? Ann Surg. 2012;255(6):1129–34.

    Article  PubMed  Google Scholar 

  28. Ueno M, Oya M, Azekura K, Yamaguchi T, Muto T. Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer. Br J Surg. 2005;92(6):756–63.

    Article  CAS  PubMed  Google Scholar 

  29. Kinugasa T, Akagi Y, Ochi T, et al. Lateral lymph-node dissection for rectal cancer: Meta-analysis of all 944 cases undergoing surgery during 1975-2004. Anticancer Res. 2013;33(7):2921–8.

    PubMed  Google Scholar 

  30. Kobayashi H, Mochizuki H, Kato T, et al. Outcomes of surgery alone for lower rectal cancer with and without pelvic sidewall dissection. Dis Colon Rectum. 2009;52(4):567– 76.

    Article  PubMed  Google Scholar 

  31. Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13(16):4807–16.

    Article  CAS  PubMed  Google Scholar 

  32. Visser M, Jiwa M, Horstman A, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer. 2008;122(11):2562–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yamamoto H, Sekimoto M, Oya M, et al. OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: Results from a multicenter clinical performance study in Japan. Ann Surg Oncol. 2011;18(7):1891–8.

    Article  PubMed  Google Scholar 

  34. Güller U, Zettl A, Worni M, et al. Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging? Cancer. 2012;118(24):6039–45.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Croner RS, Geppert C-I, Bader FG, et al. Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study. Br J Cancer. 2014;110(10):2544–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vogelaar FJ, Reimers MS, van der Linden RLA, et al. The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel lymph nodes in colon cancer patients. Ann Surg Oncol. 2014;21(12):3924–3930.

    Article  CAS  PubMed  Google Scholar 

  37. Yamamoto H, Tomita N, Inomata M, et al. OSNA-assisted molecular staging in colorectal cancer: a prospective multicenter trial in Japan. Ann Surg Oncol. 2016;23(2):391–6.

    Article  PubMed  Google Scholar 

  38. Notomi T, Okayama H, Masubuchi H, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000;28(12):E63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mori Y, Nagamine K, Tomita N, Notomi T. Detection of loop-mediated isothermal amplification reaction by turbidity derived from magnesium pyrophosphate formation. Biochem Biophys Res Commun. 2001;289(1):150–4.

    Article  CAS  PubMed  Google Scholar 

  40. Yamamoto H, Kondo M, Nakamori S, et al. JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis. Gastroenterology. 2003;125(2):556–71.

    Article  CAS  PubMed  Google Scholar 

  41. Takayama O, Yamamoto H, Ikeda K, et al. Application of RT-PCR to clinical diagnosis of micrometastasis of colorectal cancer: a translational research study. Int J Oncol. 2004;25(3):597–604.

    CAS  PubMed  Google Scholar 

  42. Miyake Y, Yamamoto H, Fujiwara Y, et al. Extensive micrometastases to lymph nodes as a marker for rapid recurrence of colorectal cancer: A study of lymphatic mapping. Clin Cancer Res. 2001;7(5):1350–7.

    CAS  PubMed  Google Scholar 

  43. Noura S, Yamamoto H, Ohnishi T, et al. Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol. 2002;20(20):4232–41.

    Article  CAS  PubMed  Google Scholar 

  44. Finke J, Fritzen R, Ternes P, Lange W, Dolken G. An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. Biotechniques. 1993;14(3):448–53.

    CAS  PubMed  Google Scholar 

  45. Yamamoto H, Murata K, Fukunaga M, et al. Micrometastasis volume in lymph nodes determines disease recurrence rate of stage II colorectal cancer: a prospective multicenter trial. Clin Cancer Res. 2016;22(13):3201–8.

    Article  CAS  PubMed  Google Scholar 

  46. Fujita S, Mizusawa J, Kanemitsu Y, et al. Mesorectal excision with or without lateral lymph node dissection for clinical stage II/III lower rectal cancer (JCOG0212): a multicenter, randomized controlled, noinferiority trial. Ann Surg. doi:10.1097/SLA.0000000000002212

    Google Scholar 

  47. Sugihara K, Kobayashi H, Kato T, et al. Indication and benefit of pelvic sidewall dissection for rectal cancer. Dis Colon Rectum. 2006;49(11):1663–72.

    Article  PubMed  Google Scholar 

  48. Matsumoto T, Ohue M, Sekimoto M, Yamamoto H, Ikeda M, Monden M. Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases. Br J Surg. 2005;92:1444–8.

    Article  CAS  PubMed  Google Scholar 

  49. Arnaud JP, Bergamasch R, Schloegel M, Ollier JC. Progress in the assessment of lymphatic spread in rectal CA. Rectal endoscopic lymphoscintigraphy.pdf. Dis Colon Rectum. 1990;33:398–401.

    Article  CAS  PubMed  Google Scholar 

  50. Shimazu K, Noguchi S. Clinical significance of breast cancer micrometastasis in the sentinel lymph node. Surg Today. 2016;46(2):155–60.

    Article  CAS  PubMed  Google Scholar 

  51. Noura S, Ohue M, Seki Y, Tanaka K. Feasibility of a lateral region sentinel node biopsy of lower rectal cancer guided by indocyanine green using a near-infrared camera system. Ann Surg Oncol. 2010;17:144–51.

    Article  PubMed  Google Scholar 

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ACKNOWLEDGEMENTS

The authors thank the many doctors and coworkers at the Gastroenterological Surgery department, Osaka University, for their helpful contributions to this study.

Funding

Funded by the Japan Society for The Promotion of Science; JSPS KAKENHI (Grant-in-Aid for Scientific Research [C]) Grant Number JP 25462055.

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Correspondence to Hirofumi Yamamoto MD, PhD.

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Miyake, Y., Mizushima, T., Hata, T. et al. Inspection of Perirectal Lymph Nodes by One-Step Nucleic Acid Amplification Predicts Lateral Lymph Node Metastasis in Advanced Rectal Cancer. Ann Surg Oncol 24, 3850–3856 (2017). https://doi.org/10.1245/s10434-017-6069-y

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