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.     

Poor Prognosis of Advanced Gastric Cancer with Metastatic Suprapancreatic Lymph Nodes

Background

Whether gastrectomy with D2 lymphadenectomy improves survival of patients with advanced gastric cancer (AGC) remains controversial. Few studies have described the pathological features of AGC with metastatic suprapancreatic lymph nodes (LN), which are the target of D2 lymphadenectomy. This study therefore aims to clarify the prognosis and clinical pathological features including the number and location of metastatic LN in AGC with metastatic suprapancreatic LN.

Methods

406 patients with AGC, who underwent gastrectomy with D2 lymphadenectomy from 1982 to 2007 at Oita University, were reviewed retrospectively with regard to presence or absence of metastatic suprapancreatic LN. The pathological factors associated with AGC with metastatic suprapancreatic LN were examined by univariate and multivariate analysis.

Results

Of 362 patients with AGC, 78 had suprapancreatic LN metastasis (21.5 %), differing significantly in terms of presence of vascular invasion and having a larger number of metastatic perigastric LN in comparison with only metastatic perigastric LN on univariate analysis. According to multivariate analysis, they were associated with presence of vascular invasion and a large number of total metastatic LN (more than two; N2≤). The overall 5-year survival rate of the AGC with perigastric LN metastasis (station 1–7) group was 37.9 % and of the AGC with suprapancreatic LN metastasis group was 12.8 %. There were significant differences in each group (P < 0.05).

Conclusions

Patients with AGC with metastatic suprapancreatic LN had a large number of total metastatic LN and poor prognosis, suggesting that it may be a systemic disease.     

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。     

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.     

Down-Regulation of Stromal Caveolin-1 Expression in Esophageal Squamous Cell Carcinoma: A Potent Predictor of Lymph Node Metastases, Early Tumor Recurrence, and Poor Prognosis

Background

Recent studies have identified loss of stromal caveolin-1 (Cav-1) expression as a new prognostic histological characteristic in various types of human cancers. However, the clinical and pathological significance of stromal Cav-1 expression in esophageal squamous cell carcinoma (ESCC) remains largely unknown. We examined Cav-1 expression in both tumor and stromal cells in ESCC tissue by immunohistochemical analysis to evaluate its clinicopathological significance and prognostic value.

Methods

A total of 110 patients with ESCC who underwent surgical resection were included in this study. The expression of Cav-1 in both tumor and stromal cells in esophageal tumor tissues was examined immunohistochemically.

Results

Cav-1 expression was found in the cytoplasm of both tumor and stromal cells. Tumor Cav-1 overexpression was observed in 37.3 % tumors, which correlated to deeper tumor invasion (p = 0.038). Down-regulation of stromal Cav-1 expression was observed in 40.9 % tumors. The stromal Cav-1 down-regulation group had more lymph node metastases and more locoregional recurrences than those with higher expression (p = 0.020 and p = 0.002, respectively). In addition, down-regulation of stromal Cav-1 expression was associated with shorter disease-free survival (p < 0.001) and overall survival (p < 0.001). Multivariate analysis revealed that down-regulation of stromal Cav-1 expression was an independent prognostic factor for both disease-free survival (p = 0.028) and overall survival (p = 0.007).

Conclusions

Down-regulation of stromal Cav-1 expression in ESCC had high malignant potential. It predicts high-risk of lymph node metastases and locoregional recurrence, and it could be a powerful prognostic marker for patients with ESCC.     

Sentinel Lymph Node Tumor Load: An Independent Predictor of Additional Lymph Node Involvement and Survival in Melanoma

Background Even though 60% to 80% of melanoma patients with a positive sentinel lymph node (SLN) have no positive additional lymph nodes (ALNs), all these patients are subjected to an ALN dissection (ALND) with its associated morbidity. The aim of this study was to predict the absence of ALN metastases in patients with a positive SLN by using features of the primary melanoma and SLN tumor load.Methods Of 71 SLN-positive patients, 52 had metastasis limited to the SLN (group 1), and 19 had 1 positive ALN after ALND (group 2). The tumor load of the SLN was assessed by measuring the total surface area by computerized morphometry. Breslow thickness, ulceration and lymphatic invasion of the primary tumor, and total SLN metastatic area were tested as covariates predicting the absence of positive ALNs.Results The mean SLN metastatic area was 1.18 mm² (group 1) and 3.39 mm² (group 2) (P = .003) and was the only significant and independent factor after multivariate analysis (P = .02). None of the patients with both a Breslow thickness <2.5 mm and an SLN metastatic area <.3 mm² had a positive ALN.Conclusions SLN metastatic area can be used to predict the absence of positive ALNs in melanoma patients. In this study, patients with a Breslow thickness <2.5 mm and an SLN tumor load <.3 mm² seemed to have no positive ALN and had excellent survival. We hypothesize that this subgroup might not benefit from ALND. Prospective larger trials, using this model and randomizing between ALND and no ALND, should confirm this hypothesis.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

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.     

Lymph Node Ratio is More Valuable than Level III Involvement for Prediction of Outcome in Node-Positive Breast Carcinoma Patients

Background We examined the relationship between different expressions of positive axillary lymph nodes (PN) and the outcomes of node-positive breast carcinoma patients to determine the best predictor(s) among these expressions and to assess whether anatomic high level involvement is an independent prognostic factor. Study Design In this retrospective study, the primary endpoints were distant recurrence (DR), locoregional recurrences (LRR), and disease-free survival (DFS). Univariate and multivariate prognostic factor analyses were carried out using survival and regression methods in the data of 704 patients with PN. Results In multivariate analysis, the number of PN, ratio of PN, log odds of PN, and level III (L-III) involvement, separately, were significant factors for DR in addition to age, tumor size, and lymphovascular invasion (LVI). In the final model including all expressions of nodal involvement, age (continuous P = 0.001; hazard ratio [HR]: 0.98; 95% confidence Interval [95% CI]: 0.96–0.99), tumor size (continuous: P < 0.0001; HR: 1.3; 95% CI, 1.2–1.5), LVI (yes vs. no: P = 0.005; HR: 1.6; 95% CI, 1.2–2.2), and ratio of PN (continuous: P = 0.02; HR: 1.03; 95% CI, 1.01–1.06) were the independent prognostic factors for DR. For LRR, ratio of PN (continuous: P = 0.001; HR: 1.02; 95% CI, 1.01–1.03) was the most important factor in addition to age (continuous: P = 0.02; HR: 0.98; 95% CI, 0.97–0.99) and tumor size (continuous: P = 0.04; HR: 1.3; 95% CI, 1.1–1.6). When patients were stratified by number categories of PN (1–3 vs. 4–9 vs. ≥ 10), there was no difference between DFSs of patients with and without L-III involvement. In contrast, when patients were stratified by L-III involvement, DFSs according to the number categories were statistically different. Conclusions Ratio of PN was more valuable than number of PN for predicting outcome in node-positive breast carcinoma patients. Level III involvement was not an independent prognostic indicator either for locoregional or for distant recurrences.     

CD44v6与胃癌淋巴结转移及预后的关系

目的 探讨CD44v6与胃癌淋巴结转移及预后的关系。方法 采用免疫组化二步法对100例进展期胃癌标本进行标记，分析CD44v6与临床病理及预后的关系。结果 胃癌原发灶CD44v6表达阳性率为64％(64／100)；CD44v6的表达随胃癌浸润深度、周围淋巴结转移而升高。结论 CD44v6在胃癌淋巴结转移中起着重要作用，可用于早期预测胃癌的转移潜能和预后。     

p16-nm23-H1蛋白在胃癌及转移淋巴结中的表达

目的观察抑癌基因p16和转移抑制基因nm23-H1蛋白在人胃癌及转移淋巴结中的表达,探讨两者在胃癌转移及预后评估中的作用.方法应用SP免疫组织化学方法检测46例原发性胃癌及69枚转移淋巴结中p16和nm23-H1蛋白表达.结果p16和nm23-H1蛋白在受检原发性胃癌中的阳性表达率分别为17.4%(8/46/)和28.3%(13/46),在转移淋巴结中的阳性率分别为15.9%(11/69)和14.5%(10/69).原发癌伴淋巴结转移组p16的阳性表达率(6.9%)低于不伴淋巴结转移组的阳性率(35.3%),差异具有显著性(P《0.05).原发癌伴淋巴结转移组nm23-H1的阳性表达率(10.3%)低于不伴淋巴结转移组的阳性率(58.8%),差异具有显著性(P《0.01).nm23-H1在乳头状腺癌中的表达率明显高于其他组织学类型(P《0.05).p16和nm23-H1表达与肿瘤大小、部位、浸润深度、Bormann分型、年龄及性别等因素无相关性(P》0.05).p16和nm23-H1在原发性胃癌及转移淋巴结中的表达无相关性(P》0.05).结论p16和nm23-H1基因蛋白对胃癌的发展及淋巴结转移有抑制作用.检测胃癌p16和nm23-H1基因蛋白对评估胃癌生物学行为、预测胃癌淋巴结转移以及预后可能具有一定的价值.     

Systematic Lymph Node Dissection for Clinically Diagnosed Peripheral Non-Small-Cell Lung Cancer Less Than 2 cm in Diameter

n = 56) or a lobectomy with radical systematic lymph node dissection group (dissection group, n = 59). Inclusion criteria were based only on preoperative clinical studies. Four tumors were larger than 2 cm postoperatively. One patient had disseminated disease, and two had intrapulmonary metastases discovered at surgery. Two patients had small-cell carcinoma. There were four with pathologic N1 disease and seven with N2 disease in the dissection group and three with N1 and eight with N2 disease in the sampling group. The numbers of local and distant recurrences were two and six, respectively, in the dissection group and two and five in the sampling group. The overall 5-year survival was 81% in the dissection group and 84% in the sampling group. No significant differences in the recurrence rate or survival was seen between the groups. Our results demonstrate that clinically evaluated peripheral non-small-cell carcinomas smaller than 2 cm in diameter do not require radical systematic mediastinal and hilar lymph node dissection.     

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.     

Anatomic Extent of Metastatic Lymph Nodes: Still Important for Gastric Cancer Prognosis

Background

Currently, gastric cancer staging systems do not consider the anatomic extent of metastatic lymph nodes (mLNs) as a prognostic factor. We therefore investigated the prognostic impact of the anatomic extent of mLNs on gastric cancer.

Methods

The prognoses of 4,043 gastric cancer patients who underwent curative resection were analyzed. Patients with mLNs in lymph node (LN) stations 1–6 (n = 1,980) comprised the perigastric LN-positive (PLN) group, and patients with mLNs in LN stations 7–12 and 14 (n = 2,063) were assigned to the extraperigastric LN-positive (ELN) group. Overall survival was estimated using the Kaplan–Meier method, and hazard ratios (HRs) were calculated by the Cox proportional hazard model.

Results

The ELN group exhibited worse survival than the PLN group (p < 0.001), although there were differences in their clinicopathological features. When patients were stratified according to tumor-node-metastasis stage, the ELN groups had unfavorable prognoses compared with the PLN groups (p < 0.05). There were significant differences in long-term survival when the nodal stage of the current staging systems were subdivided according to anatomic nodal extent (p < 0.05), although there was a strong association between the probability of having extraperigastric mLNs and N classification. In multivariate analysis using age, gender, tumor size, tumor location, histology, T classification, and the extent of mLNs as covariates, presence of extraperigastric mLNs was an independent prognostic factor (HR 1.89, 95 % CI 1.73–2.07), along with age, tumor size, tumor location, and T classification.

Conclusions

The anatomic extent of mLNs significantly affects patient prognosis. Including the anatomic extent of mLNs in the current staging system may predict gastric cancer prognosis more accurately in patients with the same stage of cancer.     

High-Level Expression of S100A4 Correlates with Lymph Node Metastasis and Poor Prognosis in Patients with Gastric Cancer

Background  

The present study investigated the clinical significance of S100 calcium binding protein A4 in the development, progression, and metastasis of gastric cancer.