Prognostic Significance of the Metastatic Lymph Node Ratio in Gastric Cancer Patients

Background  

Lymph node metastasis is considered one of the most important prognostic factors in gastric cancer. However, the optimal system for accurate staging of lymph node metastasis for patients with gastric cancer remains controversial. This study was designed to investigate the prognostic significance of the metastatic lymph node ratio (MLR), which is calculated by dividing the number of metastatic lymph nodes by the total number of nodes harvested from patients with gastric cancer.     

Prognostic Significance of Metastatic Lymph Node Ratio in T3Gastric Cancer

The fifth International Union Against Cancer tumor node metastasis (UICC TNM) classification, based on the number of metastatic lymph nodes (LN), has proved to be a reliable and objective method for predicting the prognosis of patients with gastric cancer. However, the prognosis of patients with T3 gastric cancer is still heterogeneous. This study was carried out to investigate the validity of metastatic LN ratio as a prognostic factor in T3 gastric cancer. A retrospective analysis was performed on a total of 833 patients that had either T3N1M0 (n = 504) or T3N2M0 (n = 329) gastric cancer by the fifth UICC classification. A preliminary analysis revealed the cutoff values for T3N1M0 to be 10% and for T3N2M0 to be 25%. The mean metastatic LN ratio was 9.0% for T3N1M0 cancer and 26.9% for T3N2M0 cancer. For the T3N1M0 stage, the patients who showed less than 10% of the metastatic LN ratio were grouped as N1-low with the others grouped as N1-high. For the T3N2M0 stage group, those who had less than 25% of the metastatic LN ratio were grouped as N2-low, the remainder as N2-high. The metastatic LN ratio decreased in proportion to the extent of lymphadenectomy and it increased in relation to the increasing scale of the fourth N classification. The rates of recurrence were significantly different according to the metastatic LN ratio in N1 and N2 classification of the fifth UICC classification (p < 0.05). The 5-year survival rates after gastrectomy decreased significantly by increasing the metastatic LN ratio in both T3N1M0 cancers (p =0.0026) and T3N2M0 cancers (p = 0.0057). The metastatic LN ratio was an independent risk factor for recurrence and poor prognosis. Our data suggest that the metastatic LN ratio is a significant prognostic factor for T3 gastric cancer. Furthermore, the application of the metastatic LN ratio can provide information not only about the extent of LN metastasis but also about the extent of lymphadenectomy in T3 gastric cancer.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Node-Positive Rectal Cancer

Background  The purpose of the study was to evaluate the prognostic value of metastatic lymph node ratio (LNR) in node-positive rectal cancer. Methods  A retrospective review was performed in 318 rectal cancer patients who received curative anterior resection in a single institution. Clinicopathological variables including LNR were studied in univariate and multivariate analyses by Cox regression. LNR was further studied when stratified by quartiles. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results  With median follow-up of 41 months, the 5-year disease-free survival (DFS) rate, overall survival (OS) rate, and local recurrence (LR) rate were 56.82%, 59.8%, and 11%, respectively. Multivariate analysis revealed that LNR as a continuous variable was the most significant prognostic factor for DFS, OS, and LR. On quartiles, LNR was stratified into three groups: <0.14, 0.14–0.49, and 0.5–1. The 5-year DFS rate was 72.57%, 58.54%, and 34.75% (P = 0.0001) and the 5-year OS rate was 72.19%, 61.92%, and 38.47% (P = 0.002) in the three groups, respectively. Five-year LR rate was significantly higher with LNR between 0.14 and 1 (3.6% in LNR<0.14 versus 15.6% in LNR 0.14–1, P = 0.019). Conclusions  LNR is an important prognostic factor for node-positive rectal cancers. With a cutoff of 0.14 and 0.5, node-positive rectal cancer patients could be categorized into three subsets with significant different outcomes.     

Prognostic Significance of Metastatic Lymph Node Ratio in Node-Positive Colon Carcinoma

Background The aim of this study was to evaluate the prognostic significance of the lymph node ratio between metastatic and examined lymph nodes (LNR) in patients with stage III colon cancer. Methods A review was made of 201 patients (106 men) with stage III colon cancer of R0 resection. Lymph node (LN) disease was stratified both by the American Joint Committee on Cancer and the International Union Against Cancer nodal staging system (pN) and by quartiles of the LNR. Survival curves were made by Kaplan-Meier analysis and assessed by the log rank test. Multivariate analysis was performed by the Cox proportional hazard model. Patients ranged in age from 22 to 82 (median, 59) years with median follow-up of 52 (range, 13–96) months. Results The LNR increased as a function of the number metastatic LNs (P < .0001; 95% confidence interval [95% CI], .7155–.8265). Cutoff points of LNR quartiles to be the best separating patients with regard to 5-year disease-free survival (DFS) were between quartile 1 and 2, and between 3 and 4 (pNr1, 2, and 3); the 5-year DFS according to such stratification was 83.6%, 61.1%, and 20% in pNr1, pNr2, and pNr3, respectively (P < .0001). The Cox model identified the pNr as the most statistically significant covariate: pNr2 was three times (95% CI, 1.407–6.280) and pNr3 eight times more risky than pNr1 (95% CI, 3.739–18.704). Conclusions Ratio-based LN staging, which reflects the number of LNs examined and the quality of LN dissection, is a potent modality for prognostic stratification in patients with LN-positive colon cancer.     

Prognostic Significance of Level and Number of Lymph Node Metastases in Patients with Gastric Cancer

BACKGROUND: To present data that provide some insight into the appropriateness of a nodal grouping category and its relation to survival in patients with gastric cancer. METHODS: We reviewed data of 777 patients with advanced gastric cancer who had undergone curative gastrectomy to investigate the prognostic significance of level and number of lymph node metastases. RESULTS: The prognosis of patients with gastric cancer was well correlated with the level and number of lymph node metastases. Multivariate analysis indicated that the level and number of lymph node metastases were independent prognostic indicators. Moreover, the number of lymph node metastases was an independent prognostic factor in N1, N2, and N3 patients. The most statistically significant difference in disease-specific survival was observed at a threshold of 11 lymph node metastases, yielding a chi2 value of 42.88, a hazard ratio of 2.523, at a 95% confidence interval of 1.913, 3.329 (P < .0001) by Cox proportional hazard model. On the basis of this result, patients were divided into two groups as follows: marked lymph node metastasis group (number of positive nodes > or =11) and slight lymph node metastasis group (number of positive nodes < or =10). The prognosis of patients with marked lymph node metastasis was statistically significantly worse than that with slight lymph node metastasis in N1, N2, and N3 patients. CONCLUSIONS: Both level and number were indispensable for evaluating lymph node metastasis. Therefore, addition of the number of positive nodes to the N category defined by the Japanese Classification of Gastric Carcinoma may be a useful strategy in the N staging classification in gastric cancer.     

Prognostic Significance of Lymph Node Metastases in Patients with High-Grade Appendiceal Cancer

Background  

In treating high-grade appendiceal cancer, appropriate patient selection for cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is essential. The effect of lymph node (LN) status on survival is not clear. We hypothesize that LN metastases negatively affect long-term survival.     

Prognostic Value of Lymph Node Yield and Metastatic Lymph Node Ratio in Medullary Thyroid Carcinoma

Introduction  Lymphadenectomy and thyroidectomy is standard treatment for medullary thyroid carcinoma (MTC), but the prognostic importance of the number of lymph nodes removed (lymph node yield, LNY) and the proportion of metastatic lymph nodes resected (metastatic lymph node ratio, MLNR) is unknown. We hypothesized that MTC survival is influenced by LNY and MLNR. Methods  Patients (N = 534) who underwent thyroidectomy with lymphadenectomy for MTC between 1988 and 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan–Meier method was used for univariate comparisons of survival for LNY and MLNR with a maximum follow-up of 12 years. Cox regression models adjusted for age, sex, extent of disease, tumor size, nodal status, LNY, and MLNR. Results  By univariate analysis, increasing LNY was associated with improved survival in all patients (P < 0.002) and node-positive patients (P < 0.001). In a multivariate analysis using LNY and MLNR as categorical variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), LNY (P = 0.007), and MLNR (P < 0.02); in node-negative patients: age (P = 0.002); in node-positive patients: age (P < 0.001), tumor size (P < 0.001), and LNY (P = 0.001). Using LNY and MLNR as continuous variables, significant factors influencing survival included: age (P < 0.001), tumor size (P < 0.001), and MLNR (P = 0.01); in node-negative patients: age (P < 0.001); in node-positive patients: age (P < 0.001) and tumor size (P < 0.001). Conclusion  In patients undergoing thyroidectomy and lymphadenectomy for MTC, LNY and MLNR predict poorer survival, but their impact on survival was limited to node-positive patients and was otherwise dominated by the effects of age and extent of disease. Supported by Grant Number KL2RR024144 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Presented in part at the 3rd Annual Academic Surgical Congress, February 12–15, 2008, Huntington Beach, California.     

The Metastatic Lymph Node Number and Ratio Are Independent Prognostic Factors in Esophageal Cancer

Objective  

The current American Joint Committee on Cancer staging system for esophageal cancer is based on lymph node location, irrespective of the number of involved and examined lymph nodes.     

Lymph Node Status in Patients with Submucosal Gastric Cancer

Background The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer.Methods Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients.Results Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (≥20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors <20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor <20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population.Conclusions Lymph node status can be accurately predicted on the basis of pathologic tumor diameter <20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.     

淋巴结转移比率在预测淋巴结转移乳腺癌患者预后中的价值

目的探讨淋巴结转移比率(MLNR)在预测淋巴结转移乳腺癌患者预后中的应用价值。方法回顾性分析94例接受改良根治术治疗的淋巴结转移乳腺癌患者的临床资料,并对患者生存情况及影响预后的相关因素进行分析。结果 94例患者随访时间为12~75个月,中位随访时间为64个月,5年生存率为72.34%(68/94)。总MLNR为0.31(486/1 553)。单因素分析显示原发肿瘤大小、淋巴结转移数目、ER状态、放疗与否和MLNR影响淋巴结转移乳腺癌患者的预后(P<0.05),而患者年龄、绝经与否、PR状态、内分泌治疗与否和组织学类型与预后无关(P>0.05)。多因素分析发现MLNR(OR=2.565,95%CI=1.043~6.309,P=0.040)和肿瘤大小(OR=2.220,95%CI=1.045~4.716,P=0.038)是影响淋巴结转移乳腺癌患者预后的独立因素。结论 MLNR是影响淋巴结转移乳腺癌患者的独立预后因素,且其预测效果比淋巴结转移数目更为准确和客观。     

胃癌的淋巴结清扫及意义

胃癌是目前我国死亡率较高的恶性肿瘤之一。胃癌的浸润深度（T）和淋巴结转移程度（N）是评价肿瘤分期的重要依据,UICC及日本胃癌规约均认为淋巴结转移情况是评价胃癌预后的独立且重要的因素,因此,胃癌的淋巴结清扫程度与胃癌预后关系密切。东西方学者对胃癌淋巴结清扫范围的争论已持续多年,但越来越多的学者趋向于把D2清扫术作为胃癌治疗的标准术式。     

Clinical Significance of the Metastatic Lymph-Node Ratio in Early Gastric Cancer

The metastatic lymph-node ratio has important prognostic value in gastric cancer; this study focused on its significance in early gastric cancer. In total, 1,472 patients with early gastric cancer underwent curative gastrectomy between 1992 and 2001. Of these, 166 (11.3%) had histologically proven lymph-node metastasis. Prognostic factors were identified by univariate and multivariate analyses. Metastasis was evaluated using the Japanese Classification of Gastric Carcinoma (JGC) and the Union Internationale Contre le Cancer/Tumor, Node, Metastasis (UICC/TNM) Classification. The metastatic lymph-node ratio was calculated using the hazard ratio. The cut-off values for the metastatic lymph-node ratio were set at 0, <0.15, ≥0.15 to <0.30, and ≥0.30. The numbers of dissected and metastatic lymph nodes were correlated, but the number of dissected lymph nodes and the metastatic lymph-node ratio was not related. The JGC and UICC/TNM classification demonstrated stage migration and heterogeneous stratification for disease-specific survival. The metastatic lymph-node ratio showed less stage migration and homogenous stratification. The metastatic lymph-node ratio may be a superior method of classification, which provides also accurate prognostic stratification for early gastric cancer patients.     

Risk of Limited Lymph Node Dissection in Patients with Clinically Early Gastric Cancer: Indications of Extended Lymph Node Dissection for Early Gastric Cancer

Background

Laparoscopic gastrectomy is usually indicated in T1 N0–1 early gastric cancer (EGC). Limited lymph node dissection, such as D1+, is applied in these cases. However, preoperative staging is not always correct, and the risk of undertreatment thus exists.

Methods

Patients with clinically early gastric cancer (cEGC) who underwent gastrectomy with lymph node dissection of D2 and over were selected from 4,021 patients with gastric cancer. The station numbers of all metastatic lymph nodes (MLNs) were identified, and MLNs were classified into groups 1 and 2 (including lymph nodes of second tier and over) on the basis of the system of the Japanese Gastric Cancer Association, irrespective of the number of MLNs. Clinicopathological data were compared according to the existence of lymph node metastasis and the classification of MLNs.

Results

Of 1,308 patients with cEGC who fulfilled the inclusion criteria, 1,184 (90.5 %) were diagnosed pathologically with EGC. Among 126 patients with cEGC who were diagnosed with lymph node metastasis, 93 patients had only group 1 MLNs and 33 patients had group 2 MLNs. Tumor location in the proximal third of the stomach (odds ratio 5.450) and ulceration (odds ratio 11.928) were significant factors for group 2 metastasis.

Conclusions

Extended lymph node dissection is recommended in cEGC with ulceration or disease located in the proximal third of the stomach.     

New Metastatic Lymph Node Ratio System Reduces Stage Migration in Patients Undergoing D1 Lymphadenectomy for Gastric Adenocarcinoma

Background  

The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for gastric cancer incorporates the absolute number of metastatic lymph nodes (N status) and is optimally used when ≥15 nodes are examined. The ratio of metastatic to examined nodes (N ratio) is an effective prognostic tool, but has not been examined in Western patients undergoing primarily D1 lymphadenectomy.     

Most Important Lymph Node Information in Gastric Cancer: Multivariate Prognostic Study

Background: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis.Methods: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1–6), Level II nodes (intermediate, No.7–9), and Level III nodes (distant, No.10–16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk.Results: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P < .01), total number of positive nodes (P < .01), number of positive Level I nodes (P < .01), and number of positive Level II nodes (P < .01), in addition to the tumor location (P < .05), tumor size (P < .05), gross type (P < .01), and depth of wall invasion (P < .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0–1 vs. 2) (62% vs. 19%, P < .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P < .01).Conclusions: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.