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 the Metastatic Lymph Node Ratio in Patients with Gastric Cancer

Background  

In gastric cancer, the classification of lymph node status is still a controversial prognostic factor. Recent studies have proposed a new prognostic factor (metastatic lymph node ratio: MLR) for gastric cancer patients who undergo curative resection. The present study tested the hypothesis that MLR was better than the current pN staging system by analyzing the correlation between MLR and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system, by analyzing the correlation between MLR and 5-year overall survival (OS), by comparing area under the curve (AUC), and by performing univariate and multivariate analyses for OS.     

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 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.     

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.     

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。     

Prognostic Significance of Tumor Size in T3 Gastric Cancer

Background  Clinical significance of tumor size remains elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of tumor size in T3 gastric cancer. Methods  A total of 273 patients with T3 gastric cancer who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. In terms of average value of tumor size, patients were divided into two groups according to tumor size: small-size group (SSG, tumor ≤6 cm) and large-size group (LSG, tumor >6 cm). The prognostic value of tumor size and the correlation between tumor size and other clinicopathologic factors were investigated. Results  LSG accounted for 34.8% in all patients. Tumor size was correlated with histological type, lymphatic invasion, venous invasion, and resection type. The prognosis of LSG patients was worse than that of SSG patients. Multivariate analysis showed that type of resection, status of lymph nodes, metastatic lymph node ratio, and tumor size were defined as independent prognostic factors for patients with T3 gastric cancer. A comparison between LSG patients and SSG patients showed differences in the survival of those with stage IIIB and IV disease. Conclusions  Tumor size is a simple and reliable prognostic factor for patients with T3 gastric cancer; it might be a candidate for the gastric cancer staging system.     

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.     

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.     

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.     

Clinical Significance of Splenic Hilar Lymph Node Metastasis in Proximal Gastric Cancer

Background  Prophylactic splenectomy for splenic hilar node removal is generally not advised because of the high morbidity and mortality rates and the uncertain impact on patient survival. The aim of this study was to compare the clinicopathologic characteristics and effect on survival of the following two groups: the splenic hilar lymph node metastasis group and the non-metastasis group. Methods  Three hundred and nineteen patients with proximal gastric adenocarcinoma who underwent curative total gastrectomy with simultaneous splenectomy and D2 lymph node dissection at the Samsung Medical Center between 1995 and 2004 were analyzed retrospectively. Results  Forty one patients (12.9%) had splenic hilar node metastasis. The splenic hilar metastasis group was shown to have a higher proportion of females (48.8%), Borrmann type IV (34.1%), tumor size >5 cm (82.9%), poorly differentiated adenocarcinoma (51.2%), signet ring cell carcinoma (31.7%), Lauren diffuse-type (80.5%), endolymphatic invasion (65.5%), and nerve invasion (46.4%; p < 0.05). There was no splenic hilar node metastasis in early gastric cancer. The 5-year survival rate was 11.04% for the hilar node metastasis group (p < 0.001), which was significantly lower than in the non-metastasis group, in which it was 51.57%. Multivariate analysis revealed that hilar node metastasis was an independent prognostic factor [hazard ratio 1.671; 95% confidence interval (CI) 1.075–2.595; p = 0.022]. Conclusion  Splenic hilar node metastasis was not apparent in early gastric cancer and had a very poor prognosis, even though curative resection was done, so the effectiveness of prophylactic splenectomy is uncertain.     

胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义

目的探讨胃癌淋巴管生成、淋巴管浸润及淋巴结微转移的临床意义。方法免疫组化法检测68例胃癌原发灶中D2-40的表达及其中51例胃癌的791枚淋巴结中CK20和CKpan的表达，结合患者的l临床病理特征进行综合分析。结果胃癌HE染色淋巴管浸润（LVI-HE）和D240染色淋巴管浸润（LVI-IM）的阳性率分别为66．2％（45／68）和76．5％（52／68），差异无统计学意义（P=0．118）。LVI-IM阳性率与肿瘤浸润深度（P=0．044）、TNM分期（P=0．003）及存在淋巴结转移（P=0．000）有关。68例胃癌平均淋巴管密度（LVD）为（18．19&#177;7．44）个／HP.LVD升高与LVI-HE阳性（P=0．040）、LVI—IM阳性（P=0．001）、静脉浸润（P=0．037）、TNM分期较晚（P：0．020）及存在淋巴结转移（P=0．001）有关系。LVD值≥15个／HP者近期生存率较LVD值≤14个／HP者明显降低（P=0．032）。51例胃癌HE染色和CK（CK20或CKpan）染色检出淋巴结转移率分别为74．5％（38／51）和88．2％（45／51），791枚淋巴结的转移淋巴结检出率由HE染色的32．0％（253／791）提高到CK染色的41．5％（328／791），P〈0．001。CKpan的微转移检出率明显高于CK20（P=0．003）。微转移淋巴结数量与肿瘤大小（P=0．001）、LVIHE（P=0．040）、肿瘤浸润深度（P=0．018）及TNM分期（P=0．012）有关。微转移淋巴结的检出使淋巴结转移站别及TNM分期迁移：7例N0→N1，6例N1→N2，1例N2→N3；4例Ⅰb→Ⅱ，4例Ⅱ→Ⅲa，3例Ⅲa→Ⅲb，1例Ⅲb→Ⅳ。结论D2-40及CK检测在诊断淋巴管浸润和淋巴结微转移上优于HE检查。CK20和CKpan的联合检查有利于发现微转移淋巴结。肿瘤TNM分期越晚，越易发生淋巴结微转移。LVI-IM、LVD及淋巴结微转移三者都与胃癌淋巴结转移有关。LVD值较高者近期生存率较低。