Clinical Significance of Lymph Node Ratio and Location of Nodal Involvement in Patients with Right Colon Cancer

Background/Aims: Increasing negative lymph node count has been reported to be associated with better outcomes in patients with colon cancer. The present study aimed to clarify the clinical significance of the lymph node ratio (LNR) and location of lymph node metastasis (LNM) in patients with stage III right colon cancer. Methods: We enrolled 820 patients who had undergone curative resection due to colon cancer at a single institution between 1991 and 2005. Among them, 197 underwent curative resection for T2–T4 right colon cancer. We evaluated the oncological outcomes according to LNR (quartiles) and distribution of LNM (n1 = LNM adjacent to the colon or along the vascular arcades of the marginal arteries; n2 = LNM along the major vessels; n3 = LNM near the roots of the major vessels). Results: The rates of LNM in T2, T3 and T4 right colon cancer were 11.1, 38.6 and 58.0%, respectively (p ! 0.0001). Recurrence rates were 27.3, 37.5 and 57.1% in patients with n1, n2 and n3 LNM, respectively Published online: May 10, 2011 Hirotoshi Kobayashi, MD, Assistant Professor Department of Surgical Oncology, Division of Colorectal Surgery Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519 (Japan) Tel. +81 3 5803 5261, E-Mail h-kobayashi.srg2 @ tmd.ac.jp © 2011 S. Karger AG, Basel 0253–4886/11/0283–0190$38.00/0 Accessible online at: www.karger.com/dsu D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /6 /2 01 7 5: 54 :3 3 A M Vascular High Ligation for Right Colon Cancer Dig Surg 2011;28:190–197 191 socolic excision (CME) for colon cancer has recently been proposed as well as total mesorectal excision for rectal cancer [6] . Mesocolic excision with high ligation of the main feeding artery has been a standard technique for advanced colon cancer in Japan [7, 8] . However, high ligation of the supplying arteries and the draining veins for right colon cancer is sometimes complicated because of variations in vascular branches [9, 10] . The precise indication for CME in patients with stage III right colon cancer has not been clarified. Recent studies have reported that the concept of the lymph node ratio (LNR), which is the proportion of metastatic to examined lymph nodes, is a prognostic factor in patients with stage III colorectal cancer [11–16] . On the other hand, it has been reported that the distribution of lymph node metastasis (LNM) is a prognostic factor in patients with stage III colon cancer [7] . However, LNR and the location of LNM have not been investigated simultaneously as prognostic factors in patients with stage III colon cancer. The present study aimed to clarify the value of lymph node dissection with high ligation of the primary feeding artery for right colon cancer. We also evaluated the clinical significance of the LNR and the distribution of LNM in patients with stage III right colon cancer. Patients and Methods Patients We reviewed the medical charts of 820 patients who underwent curative surgery for colon carcinoma at a single institution (the Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan) between January 1991 and December 2005. Among them, 197 underwent curative resection with high ligation of the main feeding arteries and CME for T2–T4 right colon cancer. The standard practice of nodal dissection for advanced colon cancer at our institution involves ligating the major artery to the region of resection at its origin. Resection of the right colon involves resection of the ileocolic artery and right colonic artery at their origin from the superior mesenteric artery. We usually ligate only the right branch of the middle colic artery, although the lymph nodes around the root of the middle colic artery are dissected. The resected specimen with the mesentery was stretched and pinned to a cork board. The surgeon identified the lymph nodes, isolated them and recorded both their number and distribution. In this study, the surgeons harvested the lymph nodes from the specimen to evaluate the precise location of nodal metastases; we acknowledge that this technique is not the custom in the vast majority of centers in North America or Europe. After formalin fixation, the specimens and lymph nodes were examined by the pathologist. Patients with familial adenomatous polyposis, kindred with cancer family syndrome or ulcerative colitis were excluded from this study. We evaluated the oncological outcomes according to the distribution of LNM. Location of LNM The distribution of LNM was classified as n0 (no LNM), n1 (LNM adjacent to the colon or along the vascular arcades of the marginal arteries), n2 (LNM along the major vessels) or n3 (LNM near the roots of the major vessels). Lymph Node Ratio We calculated the LNR as the proportion of metastatic to examined lymph nodes and then classified the LNRs into subgroups according to the following quartiles: 1 0 to ! 0.07, 6 0.07 to ! 0.15, 6 0.15 to ! 0.30 and 6 0.30. Follow-Up Program All patients were strictly followed up. During the first 3 years, patients were followed up every 3 months with clinical assessment and measurement of serum carcinoembryonic antigen, and every 6 months with chest X-rays and abdominal ultrasonography or computed tomography. For the next 2 years, all tests were performed every 6 months. Colonoscopy was performed 1 year after surgery and every 2 years for the next 4 years. Statistical Analysis Data were statistically analyzed using JMP 8 (SAS Institute Inc., Cary, N.C., USA). All data are expressed as means 8 standard deviation. Data concerning age and number of lymph nodes were analyzed using the Mann-Whitney U test and Kruskal-Wallis test for 2 and 3 or more groups, respectively. Associations between each parameter and LNM or recurrence were analyzed using the 2 test. Independent risk factors for LNM and recurrence were determined using logistic regression analysis after forward stepwise selection. The actuarial survival of patients was calculated using the Kaplan-Meier method. Overall survival rates in all groups were compared using the log-rank test. Cox’s proportional hazard regression analysis was applied to determine which factors independently affected postoperative survival. Forward selection was adopted in a stepwise regression procedure. Statistical significance was established at p ! 0.05 for all results.