Central lymph node metastasis is predictive of survival in advanced gastric cancer patients treated with D2 lymphadenectomy

BMC Gastroenterology - Tập 21 - Trang 1-8 - 2021
Huiwen Lu1, Bochao Zhao1, Rui Huang2, Yimeng Sun1, Zirui Zhu1, Huimian Xu1, Baojun Huang1
1Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China
2Department of Clinical Medicine of Year 2017, Dalian Medical University, Dalian, People’s Republic of China

Tóm tắt

The number of positive lymph nodes, which was defined as “N stage”, is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A “central lymph node” (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan–Meier curves. The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138–1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.

Tài liệu tham khảo

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer JClin. 2018;68(6):394–424. Rohde H, Gebbensleben B, Bauer P, Stutzer H, Zieschang J. Has there been any improvement in the staging of gastric cancer? Findings from the German Gastric Cancer TNM Study Group. Cancer. 1989;64(12):2465–81. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer. 2011;14(2):101–12. Hayashi H, Ochiai T, Suzuki T, et al. Superiority of a new UICC-TNM staging system for gastric carcinoma. Surgery. 2000;127(2):129–35. Hidaka H, Eto T, Maehara N, Jimi S, Hotokezaka M, Chijiiwa K. Comparative effect of lymph node metastasis classified by the anatomical site or by the number of nodes involved on prognosis of patients with gastric cancer. Hepatogastroenterology. 2008;55(88):2269–72. Karpeh MS, Leon L, Klimstra D, Brennan MF. Lymph node staging in gastric cancer: is location more important than number? An analysis of 1,038 patients. Ann Surg. 2000;232(3):362–71. Katai H, Yoshimura K, Maruyama K, Sasako M, Sano T. Evaluation of the new international union against cancer TNM staging for gastric carcinoma. Cancer. 2000;88(8):1796–800. Ikoma N, Estrella JS, Blum M, et al. Central lymph node metastasis in gastric cancer is predictive of survival after preoperative therapy. J Gastrointest Surg. 2018;22(8):1325–33. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11(5):439–49. Ikoma N, Blum M, Estrella JS, et al. Left gastric artery lymph nodes should be included in D1 lymph node dissection in gastric cancer. J Gastrointest Surg. 2017;21(10):1563–70. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. Mocellin S, Nitti D. Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials. Cancer Treat Rev. 2015;41(5):448–54. de Steur WO, Hartgrink HH, Dikken JL, Putter H, van de Velde CJ. Quality control of lymph node dissection in the Dutch Gastric Cancer Trial. Br J Surg. 2015;102(11):1388–93. Liu JY, Deng JY, Zhang NN, et al. Clinical significance of skip lymph-node metastasis in pN1 gastric-cancer patients after curative surgery. Gastroenterol Rep. 2019;7(3):193–8. Choi YY, An JY, Guner A, et al. Skip lymph node metastasis in gastric cancer: is it skipping or skipped? Gastric Cancer. 2016;19(1):206–15. Park SS, Ryu JS, Min BW, et al. Impact of skip metastasis in gastric cancer. ANZ J Surg. 2005;75(8):645–9. Son T, Hyung WJ, Kim JW, et al. Anatomic extent of metastatic lymph nodes: still important for gastric cancer prognosis. Ann Surg Oncol. 2014;21(3):899–907. Chen J, Chen C, He Y, Wu K, Wu H, Cai S. A new pN staging system based on both the number and anatomic location of metastatic lymph nodes in gastric cancer. J Gastrointest Surg. 2014;18(12):2080–8. Griniatsos J, Yiannakopoulou E, Gakiopoulou H, et al. Clinical implications of the histologically and immunohistochemically detected solitary lymph node metastases in gastric cancer. Scand J Surg. 2011;100(3):174–80. Yamashita H, Seto Y, Sano T, Makuuchi H, Ando N, Sasako M. Results of a nation-wide retrospective study of lymphadenectomy for esophagogastric junction carcinoma. Gastric Cancer. 2017;20(Suppl 1):69–83. Cense HA, Sloof GW, Klaase JM, et al. Lymphatic drainage routes of the gastric cardia visualized by lymphoscintigraphy. J Nucl Med. 2004;45(2):247–52. Ajani JA, D’Amico TA, Almhanna K, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2016;14(10):1286–312. Tsuburaya A, Mizusawa J, Tanaka Y, Fukushima N, Nashimoto A, Sasako M. Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg. 2014;101(6):653–60. Lee J, Lim DH, Kim S, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012;30(3):268–73. Wang Y, Yu YY, Li W, et al. A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis. Cancer Chemother Pharmacol. 2014;73(6):1155–61. Xu HB, Huang F, Su R, Shen FM, Lv QZ. Capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOXs) in advanced gastric cancer: meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2015;71(5):589–601. Wang Y, Zhuang RY, Yu YY, et al. Efficacy of preoperative chemotherapy regimens in patients with initially unresectable locally advanced gastric adenocarcinoma: capecitabine and oxaliplatin (XELOX) or with epirubicin (EOX). Oncotarget. 2016;7(46):76298–307.