Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer

BACKGROUND: Skip metastasis to mediastinal lymph nodes is a well-known phenomenon in non-small cell lung cancer (NSCLC). Little is reported in the literature about its clinical importance. It is still under discussion whether any prognostic differences exist between resected NSCLC with either skip metastases or continuous mediastinal lymph node metastases (N2). PATIENTS AND METHODS: We analyzed retrospectively the data of 45 patients with a pN2-stage, who underwent resection for NSCLC. Seventeen of these patients (37.8%), showing no metastatic involvement of hilar (N1) lymph nodes, were compared to the remaining 28 patients with infiltration of hilar nodes (N1) as well as N2 nodes. RESULTS: Multivariate analysis showed no statistically significant difference between the skip metastasis and the continuous N2 group regarding sex, age, histology, T- or M-status. The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe (n = 12, 71%) compared to the lower lobe (n = 5, 29%). This difference was not statistically significant. In patients with a non-continuous lymph node spread, 29 out of 119 resected mediastinal lymph nodes were infiltrated (1.7 per patient, range: 1-10). Compared to 83 metastatic involved lymph nodes out of 198 resected mediastinal nodes (three per patient, range: 1-10) in patients with involvement of N1 and N2 nodes (P = 0.034, Mann-Whitney test). The 5-year survival rate of pN2 patients with skip metastasis was 41% compared to 14% in patients with involvement of N1 and N2 nodes (P = 0.019). CONCLUSIONS: pN2 patients with mediastinal lymph node skip metastasis have a more favorable prognosis compared to pN2 patients with continuous infiltration of the regional lymph nodes. Patients with a continuous lymph node involvement show an increased number of infiltrated mediastinal lymph nodes per patient compared to patients with a non-continuous spread. Skip metastasis is an independent prognostic factor of survival. The presence of skip metastasis seems to be a unique subgroup of pN2 disease in NSCLC.     

Analysis of risk factors for skip lymphatic metastasis and their prognostic value in operated N2 non-small-cell lung carcinoma.

BACKGROUND: The aim of this study is to report a series and to analyze risk factors for skip lymphatic metastasis an their prognostic value in operated N2 non-small-cell lung carcinoma. METHODS: From 1997 to 2002, 142 patients classified pN2 were included in the study. Tumours were classified according to the TNM classification. Skips metastases were defined by the cases of N2 disease without lobar and interlobar and hilar lymph node involvement. A skip (+) and a skip (-) group were defined. Characteristics of tumours, ganglionar involvement and survival were analysed in both groups. RESULTS: Forty-two patients fulfilled the criteria for skip metastasis. The average number of mediastinal lymph nodes resected by patient was similar in both groups, whereas more intrapulmonary nodes were dissected in the skip (-) group (4.7 +/- 3 vs 3 +/- 3; p < 0.002). The ratio of involved to resected lymph nodes was 0.47 +/- 0.27 in the skip (-) group vs 0.23 +/- 0.20 in the skip (+) group (p < 0.0001). In the skip (+) group, 85% of the patients presenting with a right upper lobe tumour had involvement of the superior mediastinal lymph nodes against 40% in the skip (-) group. The 5-year survival rate was 48% in the skip (-) group vs 37% in the skip (+) group (p = 0.49). In multivariate analysis, incomplete resection, tumour size, extended resection and pT were significant prognostic factors. CONCLUSIONS: Skip metastasis are frequent in non-small-cell lung cancer and complete dissection of hilar and mediastinal lymph nodes should remain the surgical standard procedure for this disease. However, skip metastasis are not an independent prognostic factor in survival.     

非小细胞肺癌纵隔淋巴结跳跃性转移的研究

目的 探讨非小细胞肺癌（NSCLC）纵隔淋巴结跳跃性与非跳跃性与非跳跃性转移的临床特点及预后的差异。方法 以1982-1994年间我院行手术治疗的176例ⅢA期有纵隔淋巴结转移的NSCLC患者为研究对象,其中53例不伴有肺门淋巴结转移,称为跳跃组;123例伴有肺门淋巴结转移,称为非跳跃组,将纵隔淋巴结分为3个区域,分析两组患者淋巴结转移范围及其与生存率的关系。结果 在跳跃组中,有49例（92.5%)纵隔淋巴结转移局限于1个区域（L1）,而在非跳跃组中有45例（36.6%),纵隔淋巴结转移扩至2或3个区域L2或L3）,跳跃组的5年生存率为29.3%,高于非跳跃组（12.2%,P=0.038),且在同一L1上,跳跃组5年生存率（32.1%)亦高于非跳跃组（15.3%,P=0.042)。结论 NSCLC患者纵隔淋巴结跳跃性转移为纵隔淋巴结转移病变中独特的一个亚群。     

Prognostic implication of metastasis limited to segmental (level 13) and/or subsegmental (level 14) lymph nodes in patients with surgically resected nonsmall cell lung carcinoma and pathologic N1 lymph node status

BACKGROUND:

In patients with nonsmall cell lung carcinoma (NSCLC) who have with pathologic N1 (pN1) lymph node status, the prognostic significance of segmental lymph node (level 13) metastasis and/or subsegmental lymph node (level 14) metastasis is unknown.

METHODS:

Lymph node metastasis patterns were analyzed in 230 patients with NSCLC who had pN1 status. Clinical outcomes were examined for 230 patients with pN1 status and 700 patients with pN0 status. The pN1 group was stratified into 4 subgroups according to the highest level of lymph node involvement.

RESULTS:

The 5‐year disease‐free survival (5DFS) rates for pN1 and pN0 patients were 50.1% and 90.5%, respectively. The highest level of lymph node involvement was a significant prognostic indicator; the 5DFS rates for patients with pN1 status who had level 13/14, lobar (level 12), interlobar (level 11), and hilar (level 10) lymph node metastasis were 69.4%, 46.4%, 46.7%, and 37%, respectively. Patient outcomes were significantly worse for those with pN1 status who had only level 13/14 lymph node metastasis than for patients with pN0 status (P = .0034), and outcomes were significantly worse for patients with pN1 status who had level 11/12 lymph node metastasis than for patients who had only level 13/14 lymph node metastasis (P = .021). The median number of level 13/14 lymph nodes examined was 3 (range, 0‐22 level 13/14 lymph nodes), and metastases to these lymph nodes were detected in 61% of patients who had pN1 status. A single lymph node pN1 disease, single‐level pN1 status, and squamous cell carcinoma histopathology also were indicators of a better patient outcome.

CONCLUSIONS:

The current results indicated that the highest level of lymph node involvement may be used to stratify the outcome of patients who have NSCLC with pN1 status. Patients with pN1 status who had only level 13/14 lymph node metastasis had an intermediate 5DFS rate between that of patients with pN0 status and other patients with pN1 status. Routine examination of level 13/14 lymph nodes is important for accurate pathologic staging and for the predicting clinical outcome of patients with NSCLC. Cancer 2012. © 2012 American Cancer Society.     

Significance of immunohistochemical c-ErbB-2 product localisation pattern for prognosis in human breast cancer

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified, including c-ErbB-2. In this study, expression of c-ErbB-2 in breast carcinoma was correlated with axillary lymph node metastases and disease outcome. The expression of c-ErbB-2 oncoprotein was analysed in 315 tumor specimens of infiltrating ductal carcinoma of breast. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. These patients also had axillary lymph nodes sampling. The expression of c-ErbB-2 oncoprotein was analysed immunohistochemically. Over expression of c-ErbB-2 were observed in 39.36% tumors. Axillary lymph node metastasis had significant correlation with intensified positivity of c-ErbB-2. C-ErbB-2 positive patients did show resistance to chemotherapy when compared for recurrence and distant metastases following surgery (p< 0.05). At a median follow-up of 48 months in c-ErbB-2 positive patients, the overall survival was 3.0 years and disease free survival was 2.5 years. c-ErbB-2 negative tumor patients showed a far better survival. In this group the overall survival was 4.44 years and the disease free survival was 3.78 years. These findings reinforce the view that c-ErbB-2 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.     

Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases.

PURPOSE: The purpose is to identify biological markers that predict brain metastasis and treatment outcome in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Samples were obtained from the primary tumors, lymph nodes, and brain metastases of 29 patients with NSCLC who had undergone resection of both the pulmonary tumors and the brain lesions. Samples from 29 patients matched for age, sex, and histology whose pulmonary tumors were resected served as controls. Samples were stained with H&E as well as immunohistochemical stains for epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX-2), and BAX. Comparisons were made between patients with and without brain metastasis. Independent investigators determined the percentage of positive cells. RESULTS: There was positive correlation in expression of all three biomarkers between primary lung tumors and lymph node metastases. Significantly higher levels of EGFR were found in lymph node metastases in the control group (P = 0.0147). COX-2 expression in brain lesions correlated with expression in primary tumors (P = 0.023). BAX levels were lower in poorly differentiated tumors in lymph node metastases in the control group (P = 0.01) and in brain metastases (P = 0.045). Low EGFR expression and high COX-2 expression in lymph node metastasis were associated with poorer treatment outcome. CONCLUSIONS: Expression of EGFR, COX-2, and BAX in primary lung tumors did not differ between patients with brain metastases from NSCLC and those without brain metastases. These three biomarkers cannot be used to predict brain metastasis. Studies of other biomarkers are under way in an effort to predict brain metastasis among patients with NSCLC.     

RELATIONSHIP BETWEEN LYMPH NODE METASTASES IN ESOPHAGEAL CARCINOMA AND ITS PROGNOSIS

The prognosis of patients with respectable esophageal carcinoma still remains poor. The 5-year survival rates range from 20% to 36% after intentionally curative surgery[1-3]. Early metastatic relapse after complete resection of an apparently localized primary tumor indicates that micro- metastastic tumor cells spread at the time of surgery, undetected by current staging methods and by routine histopathology. The lymph node metastases play a pivotal role in patients with esophageal cancer. It i…     

RT-PCR法检测MUC1 mRNA诊断肺癌纵隔淋巴结隐匿转移

目的：探讨对常规病理检查漏诊的肺癌纵隔淋巴结转移病灶的诊断方法。方法：应用逆转录聚合酶链反应法（RT－PCR），检测pN0.1期非小细胞肺癌患者（NSCLC）纵隔淋巴结中MUC1基因mRNA的表达。结果：5枚肺良性疾病的局部淋巴结无MUC1基因mRNA表达，5枚经病理检查证实有淋巴结转移癌的NSCLC纵隔淋巴结中均检测中MUC1mRNA表达，实验组19例患者的78例枚纵隔淋巴结中有6枚检测到MUC1mRNA表达，从而诊断为纵隔淋巴结隐匿转移。结论：应用RT－PCR法检测纵隔淋巴结中MUC1基因mRNA的表达可以提高临床对肺癌纵隔淋巴结转移诊断的准确性。     

Ⅲa-N2非小细胞肺癌纵隔淋巴结转移综合模式的预后价值

  目的  研究跳跃转移与肺叶特异性转移对Ⅲa-N2非小细胞肺癌（non small cell lung cancer,NSCLC）的预后意义。  方法  天津医科大学肿瘤医院2008年1月至2009年12月行完全切除和系统淋巴结清扫的218例pN2期NSCLC被纳入本研究。根据有无N1区淋巴结转移将分为连续转移与跳跃性转移;根据纵隔淋巴结转移范围是否超出肺叶特异性区域分为纵隔广泛转移与肺叶特异性转移。对各组的总生存（overall survival,OS）和无病生存（disease free survival,DFS）进行了比较。  结果  全组患者的5年OS为21.6%,5年DFS为16.8%。跳跃性转移及连续转移病例的5年OS分别为37.6%和22.0%（P =0.008）;DFS分别为29.1%和15.0%（P =0.022）。肺叶特异性转移和广泛转移的5年OS分别为38.3%和20.4%（P =0.005）;DFS分别为28.4%和15.1%（P =0.009）。根据两者的组合将所有患者进一步分为3组:仅有跳跃性转移和肺叶特异性转移（A组）,发生连续转移或者纵隔广泛转移中的一项（B组）;既有连续转移又有纵隔广泛转移（C组）。3组的5年OS分别为47.1%,28.1%和16.6%（P =0.001）;5年DFS分别为35.2%,20.8%和11.2%（P =0.002）。多因素分析表明,这种综合转移模式是OS和DFS的独立预后因素。  结论  淋巴结转移的综合模式是Ⅲa-N2的一种独立的预后因素,在评价患者预后及筛选术后治疗患者时应该将这种综合模式考虑在内。      

Clinical implications of axillary sentinel lymph node 'micrometastases' in breast cancer.

AIMS: The aim of this study was to determine, from a series of cases, the frequency and prognostic factors of invasion of non-sentinel lymph nodes when the axillary sentinel lymph node contains a metastasis < or =2 mm, and thereby select a population in which completion axillary dissection could be omitted. METHODS: Between July 1996 and July 2003, 62 patients, which axillary sentinel lymph node contained a metastasis < or =2 mm had an evaluation of the axillary non-sentinel lymph nodes. Eleven patients had also an evaluation of internal mammary lymph nodes. RESULTS: Eleven patients had axillary non-sentinel lymph node invasion: six by metastases < or =2 mm and five by macrometastases. When internal mammary lymph nodes were also concerned, nodal invasion apart from the axillary sentinel lymph node was seen in 14 patients. Vascular lymphatic invasion was the only factor, statistically significant, linked to non-sentinel lymph node invasion (p = 0.02). CONCLUSION: Whatever the size or method of histological detection (pN1mi or pN0(i+)), the presence of a metastasis < or =2 mm in the axillary sentinel lymph node leads us to carry out completion axillary dissection to optimize staging and loco-regional control of the disease.     

乳腺癌腋窝淋巴结跳跃式转移的临床病理研究

目的 探讨乳腺癌腋窝淋巴结跳跃式转移与患者临床病理特征的关系及其对预后的影响.方法 回顾性分析1502例行完全腋窝淋巴结清除术乳腺癌患者的临床资料,观察腋窝淋巴结跳跃式转移的发生规律,分析其与患者临床病理特征的关系及对预后的影响.结果 有淋巴结转移者814例,其中腋窝淋巴结跳跃式转移者119例,占14.6%;跳跃式转移中,最常见的是从第Ⅰ、Ⅱ水平跳过第Ⅲ水平至腋尖,发生率为5.2%.跳跃式转移的发生与患者的年龄、肿瘤大小、临床分期以及雌激素受体状态均无关(均P＞0.05).Ⅰ～Ⅱ期患者中,跳跃式转移组的10年无病生存率较非跳跃式转移组低(58.5%∶ 77.3%,P＝0.003);Ⅲ期患者中,两组的10年无病生存率差异无统计学意义(50.0%∶ 57.6%,P＝0.457).Cox多因素分析显示,肿块大小、淋巴结转移数目、淋巴结结外是否受侵及是否发生跳跃式转移,是影响患者预后的独立因素.结论 某些常见的临床病理指标尚不能准确地预测腋窝淋巴结跳跃式转移的发生;早期乳腺癌发生跳跃式转移者预后差,对其应坚持严格而规范的治疗.     

Prognostic implications of cell cycle-related proteins in primary resectable pathologic N2 nonsmall cell lung cancer

BACKGROUND: Patients who have pathologic N2 (pN2) nonsmall cell lung cancer (pN2 NSCLC) represent a heterogeneous group with regard to prognosis and treatment. Molecular features of NSCLC seem to be of interest. For the current study, to select an appropriate therapeutic strategy for each patient, patients with N2 NSCLC were stratified into homogenous subgroups according to the expression profiles of cell cycle-related markers. METHODS: The expression levels of retinoblastoma protein (pRb), cyclin D1, p16, p53, and p21 proteins and values of the Ki-67 labeling index were evaluated in 61 primary surgically resected tumor specimens from patients with pN2 NSCLC using immunohistochemistry. The prognostic impact of these markers on overall survival was analyzed in both univariate and multivariate analyses. RESULTS: In univariate analysis, p21, p16, and Ki-67 were correlated significantly with survival. In multivariate analysis, only p21 and p16 influenced survival. Indeed, the group of patients with pN2 NSCLC who were positive for p21 and p16 had the most favorable overall survival (P = .001) and were correlated significantly with the clinical lymph node (cN) status (cN2 disease; P = .008). Moreover, no significant difference in survival was observed between patients with cN0/cN1 disease and patients with cN2 disease within the group (P = .4333). CONCLUSIONS: Loss of control of cell-cycle checkpoints is a common occurrence in pN2 NSCLC. Functional cooperation between different cell-cycle regulators constitutes another level of regulation in cell growth control and tumor suppression. Preoperative patients with pN2 NSCLC, even those with cN2 disease, who have positive p21 and p16 protein expression in their primary tumors are expected to have a favorable postoperative prognosis and may be candidates for primary resection.     

非小细胞肺癌淋巴结转移规律分析

背景与目的:淋巴结转移是肺癌最常见的转移途径,影响分期和预后,胸内淋巴结(包括肺门和纵隔)转移是影响肺癌预后的重要因素之一。本研究旨在对非小细胞肺癌(non-small cell lung cancer,NSCLC)术后淋巴结转移特点进行分析,为手术选择淋巴结清扫范围提供参考依据。方法:205例NSCLC手术病例,比较胸内各组淋巴结转移情况,从肿瘤原发部位和肿瘤组织类型两方面比较各分组之间淋巴结转移率及跳跃性转移率的差异。结果:205例NSCLC术中共清扫胸内淋巴结977组共3 577枚,平均每例17.4枚。其中220组共508个淋巴结存在转移,有胸内淋巴结转移病例98例,转移率为47.8%。发生跳跃性转移35例,转移率为17.1%。第4、5、7、10、11组淋巴结转移频度较高。肺上叶癌比肺下(中)叶癌更容易发生跳跃性转移。腺癌的淋巴结转移率明显高于鳞癌。结论:NSCLC的淋巴结转移多数是按肺内淋巴结到肺门淋巴结再到纵隔淋巴结的顺序进行逐级转移,纵隔淋巴结的跳跃性转移比较常见。NSCLC的淋巴结转移特点与肿瘤的原发部位、肿瘤组织类型有密切关系。手术应根据淋巴结转移规律对胸内淋巴结进行系统性清扫,特别注意转移频率较高的第4、5、7、10、11组淋巴结。     

Five-year survivors with resected pN2 nonsmall cell lung carcinoma

BACKGROUND: Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow-up periods. METHODS: Between 1981-1990, 178 patients with pN2 nonsmall cell lung carcinoma underwent complete resection with systemic lymph node dissection. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors were compared. RESULTS: Gender, the side that was operated on, location of the tumor, histologic type, or surgical procedure were not related to the ratio of 5-year survivors. However, T classification, skip metastasis, and the number of levels involved were associated with the ratio significantly. The authors also found that the location of the involved lymph node(s) affected the ratio. CONCLUSIONS: Even in the presence of pN2 disease, lung carcinoma patients with T1 tumors, skip metastasis, or single level mediastinal lymph node involvement, especially Level 4, Level 5, or Level 6 lymph nodes, had a relatively favorable prognosis and may be candidates for primary resection.     

Prognostic factors in patients with squamous oesophageal cancer associated with solitary lymph node metastasis after oesophagectomy and extended lymphadenectomy

It is not fully understood whether oesophageal cancer, associated with solitary lymph node metastasis, is still a local disease or already a systemic one. Among 283 patients with squamous oesophageal cancer who underwent oesophagectomy and 3-field lymphadenectomy, 37 patients had single metastasized nodes. Clinicopathologic factors, following Japanese Guideline for the Clinical and Pathological studies on Carcinoma of the Esophagus, related to survival and pre-operative predictability of nodal involvement was studied. Five-year survival was 48%. Initial pattern of recurrence was mostly haematogenous. Among the factors related to survival, grade of lymph node metastasis (pN1 vs. pN2, pN3, p=0.006) was more closely related than depth of invasion (pT1, pT2 vs. pT3, pT4, p=0.037). Five-year survival was 71.7% for pN1 patients, whereas it was 22% for pN2 or pN3 patients. Of the metastasized nodes 65% were <10 mm, and 27% was <5 mm in the maximum diameter. Oesophageal cancer is still a local disease in half of the patients with a solitary metastasized node. For these patients, dissection along the recurrent laryngeal nerve is necessary to retrieve the node possibly metastasized.     

肺癌淋巴结隐匿性转移的基因诊断及预后研究

目的 探讨非小细胞肺癌（NSCLC）纵隔淋巴结隐匿性转移的基因诊断方法,并评价其对预后的意义。方法 应用逆转录聚合酶链反应（RT－PCR）技术,对37例pN0 NSCLC（Ⅰa-Ⅱb期）的168枚纵隔淋巴结标本中的黏蛋白1（MUC1）基因mRNA表达情况进行检测。对照组为同期经手术治疗的患者,其中阴性对照淋巴结30枚（取自14例肺良性病变）,阳性对照标本30个（15例NSCLC的肿瘤标本和病理诊断为转移癌的NSCLC纵隔淋巴结15枚）。通过x^2检验,比较预后差别。结果 阴性对照组均无MUC1 mRNA表达,特异度1005;阳性对照组30个标本中,26个有MUC1 mRNA表达,灵敏度86.7%。实验组中12例患者的16个标本有MUC1 mRNA表达,占9.5%,其TNM分期上调为Ⅲa。MUC1 mRNA表达阴性组3年生存率（88.0%）高于MUC1 mRNA阳性组（58.3%,P＜0.05）。结论 应用RT－PCR法检测MUC1 mRNA的表达可诊断肺癌纵隔淋巴结隐匿性转移;纵隔淋巴结隐匿性转移可能与pN0肺癌预后不良有关。     

Prognostic role of p‐mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer

Despite the great interest in mammalian target of rapamycin (mTOR) as a potential anticancer therapy target, the prognostic role of mTOR in gastric cancer has not been elucidated. In this study, we investigated mTOR expression in gastric cancer tissues and in metastatic lymph nodes and examined its association with clinical outcome. A total of 290 patients with pT2b gastric cancer were enrolled in this study. Patients were divided into 3 groups according to metastatic lymph node status: Group 1 contained 96 patients without lymph node metastasis, Group 2 contained 102 patients with a few (1–2) metastatic lymph nodes and Group 3 contained 92 patients with extensive (>16) lymph node metastasis. Phosphorylated mTOR expression was determined immunohistochemically using tissue microarrays. p‐mTOR expression was observed in 36.5% of the gastric cancer tissues in Group 1, 39.2% in Group 2 and 60.9% in Group 3. A significant correlation was found between p‐mTOR expression in gastric cancer tissues and in metastatic lymph nodes. The Borrmann type in Group 1, perineural invasion and p‐mTOR expression in metastatic lymph nodes in Group 2 and p‐mTOR expression in metastatic lymph nodes in Group 3 were found to be independent prognostic factors of disease‐free survival. The 5‐year disease free survival rate of Group 2 patients was 84.4% in negative p‐mTOR and 66.1% in positive p‐mTOR expression in metastatic lymph nodes (p = 0.015). The 5‐year disease free survival rate of Group 3 patients was 37.3% in negative p‐mTOR and 14.9% in positive p‐mTOR expression in metastatic lymph nodes (p = 0.037). There was a linear correlation between the rate of tumor recurrence and mTOR expression scores in metastatic lymph nodes. In pT2b gastric cancer, p‐mTOR expression in gastric cancer is associated with the extent of lymph node metastasis, and p‐mTOR expression in metastatic lymph nodes is correlated with poor disease‐free survival. mTOR may harbor significant potential for a prognostic biomarker and therapeutic target for gastric cancer treatment.     

Lymphadenectomy in gastric cancer: influence on prognosis of lymph node count

To better understand the role of the number of lymph nodes retrieved on long-term outcome of gastric cancer treatment, 154 patients who had undergone curative resection, with dissection of >15 nodes were retrospectively studied. Dissection of perigastric and extraperigastric lymph nodes, defined as 'extended' (>26 nodes dissected) in 39 cases and 'limited' (< or = 26 nodes dissected) in 115 cases, was performed. A total of 3479 lymph nodes (mean 22.6 per specimen), were dissected and of these 721 showed metastases. A mean of 8.1 lymph node metastases, per metastatic case, was found. Regression analysis showed no independent factor associated with the extent of lymphadenectomy. Depth of wall invasion (p=0.000) and histological growth pattern (p=0.044) were independently associated with the number of lymph nodes involved (pN0, pN1 1-7, pN2 >7). The cumulative 5-year survival rate was 47% in patients without lymph node metastases; 29% in those with 1-7 nodes involved and 17% in those with >8 nodes involved (p=0.002). Receiver operating characteristic (ROC) curve analysis, in 65 nodenegative cancer cases, demonstrated an area under the curve for vital status (alive or dead) of 0.602 (95% CI: 0.473 - 0.721). All node-negative cases with a number equivalent to or exceeding the cutoff point of 23 nodes were alive. ROC analysis showed 11 to be the cutoff number of metastasized lymph nodes in correlation with vital status. Almost all those patients in whom the number of positive nodes was equivalent to, or exceeded the cutoff point had died (area under the ROC curve 0.633; 95% CI: 0.524 - 0.733). ROC analysis showed that the cutoff lymph node ratio, in relation to vital status, was 0.33. The majority of patients at or above this cutoff point had died (area under ROC curve 0.682; 95% CI: 0.574 - 0.776). Multivariate survival analysis showed that lymph node ratio was the only independent prognostic factor (p=0.001). The present findings suggest that, in lymphadenectomy with at least 15 nodes, the number and status of regional nodes dissected, irrespective of the location, provide reliable prognostic information on curatively resected gastric carcinomas.     

Prognostic Impact of the Number of Metastatic Lymph Nodes on the Eighth Edition of the TNM Classification of NSCLC

IntroductionCurrent nodal staging of NSCLC is defined only by anatomical location of lymph nodes (LNs). The aim of this study is to investigate prognostic impacts of the number of metastatic LNs by stratifying the present N classification.MethodsWe analyzed 1989 patients with NSCLC who underwent complete resection by lobectomy or pneumonectomy involving dissection of the hilar and mediastinal LNs from 2003 to 2012. We classified patients according to the number of metastatic nodes and stations and their current category of metastatic LNs. We analyzed the overall survival in each group and assessed the survival impact of the combination of them.ResultsIn the multivariate analyses of all patients, pathological N1 (pN1) (reference [ref.] pN2) and single-node metastasis (ref. multiple-node) were independent prognostic factors whereas single-station metastasis (ref. multiple-station) was not. In the respective multivariate analyses of pN1 and pN2 disease, multiple-node metastasis (ref. single-node) was an independent prognostic factor in pN1 disease (hazard ratio: 1.41, p = 0.04), but not in pN2 disease. Investigation for other boundaries of a number of metastatic LNs of three or more (ref. one to two), four or more (ref. one to three), and five or more (ref. one to four) found that all of them were independent prognostic factors in both pN1 and pN2 diseases.ConclusionsThe number of metastatic LNs had a strong impact on survival in addition to the current pN classification. To clarify its prognostic impact, further study is needed in other datasets including patients treated by nonsurgical modalities.