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.
Similar content being viewed by others
REFERENCES
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.
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.
Enker WE. Potency, cure, and local control in the operative treatment of rectal cancer. Arch Surg. 1992;127(12):1396–401.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Uehara K, Nagino M. Neoadjuvant treatment for locally advanced rectal cancer: a systematic review. Surg Today. 2016;46(2):161–8.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Notomi T, Okayama H, Masubuchi H, et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000;28(12):E63.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
Shimazu K, Noguchi S. Clinical significance of breast cancer micrometastasis in the sentinel lymph node. Surg Today. 2016;46(2):155–60.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-017-6069-y