Factors correlated with number of metastatic lymph nodes in gastric cancer

Objective: We had previously reported a reasonable categorization of the number of positive lymph nodes (LN: 0, 1–4, 5–8, and > 8) as a prognostic indicator. This study was an extension, to see which factors correlated with number of positive lymph nodes. Methods: A total of 533 patients with gastric adenocarcinoma, who underwent curative surgery between January 1988 and December 1995, were entered into this study. Patients were divided into four groups according to metastatic LN number (0, 1–4, 5–8, and > 8). Their survival and clinicopathological factors were analyzed. Results: A total of 16,457 LNs, with an average of 30.9 per specimen, were removed, of which 1686 (10.2%) showed metastases. The 5-yr cumulative survival rate decreased as the number of metastatic LNs increased, i.e ., 91.3% for LN 0; 67.4% for LN 1–4; 37.2 for LN 5–8, and 14.1% for LN > 8. Multivariate analyses showed that depth of cancer invasion (odds ratio: 2.4), gross appearance (odds ratio: 1.9), size (odds ratio: 1.9), and location (odds ratio: 1.4) of tumor were four independent factors correlated with the number of metastatic LNs. Number of metastatic LNs increased with advanced Japanese nodal stage and UICC-TNM stage. Conclusions: Depth of tumor invasion, and gross appearance, size, and location of tumor were four pathological factors independently correlated with number of metastatic LNs in gastric cancer.     

胃癌淋巴结转移灶与原发灶P-糖蛋白的表达及意义

目的:探讨P-糖蛋白(P-glycoprotein,P—gp)在胃癌淋巴结转移灶与原发灶表达水平的差异及其与胃癌临床病理特征的关系.方法:应用免疫组化的方法检测19例伴有淋巴结转移的胃癌患者的淋巴结转移灶、胃癌原发灶和正常胃黏膜的P—gp表达.结果:淋巴结转移灶P-gp表达的阳性率高于原发灶(84.20％ vs 52.63％,P<0.05);淋巴结转移灶P-gp表达与患者性别、年龄、肿瘤分化程度和浸润深度无关;胃癌原发灶P-gp的表达与胃癌组织分化程度和浸润深度有关(P<0.05),与性别和年龄无关.P-gp表达阳性率在高、中分化者较低分化者高,肿瘤浸润未达浆膜者高于已穿越浆膜者.结论:胃癌淋巴结转移灶的P-gP表达高于原发灶,淋巴结转移灶与原发灶P-gp表达和胃癌临床病理特征的关系不同.     

Association of the number of metastatic perigastric lymph nodes with long-term survival in gastric cancer

BACKGROUND/AIMS: The presence of metastases in lymph nodes is an important prognostic factor in patients with gastric cancer. Currently, the total number of metastatic lymph nodes (MLN) is thought to be more prognostically significant than the anatomical distribution of MLN. METHODOLOGY: The associations of the total number of MLN and of the number of perigastric (PG) MLN with long-term survival were retrospectively evaluated using uni- and multivariate analysis in 481 nodepositive gastric cancer patients who underwent potentially curative resections. RESULTS: The number of PG MLN was a better prognostic indicator than the total number of MLN (indices of correlation 0.2908 and 0.3424, respectively). Good surgical results were obtained in patients with 5 PG MLN or fewer. CONCLUSIONS: The number of perigastric metastatic lymph nodes is a more conveniently obtained and reliable prognostic factor than the total number of metastatic lymph nodes in patients with node-positive gastric cancer.     

Paracortical activity of the regional lymph nodes as a prognostic determinant in gastric carcinoma

One hundred and thirty eight gastric carcinomas were assessed histologically with special attention focused on the nuclear grade of the tumor, the stromal lymphocyte reaction, and the morphology of the paracortical areas of the regional lymph nodes. Nuclear grade of the carcinoma was closely correlated with the 5-year survival rate of the patient, but no favorable prognostic influence could be attributed to the stromal lymphocyte reaction. The activity of the regional lymph node paracortex was directly positively correlated with the survival and inversely related to the appearance of the nodal metastases which were ominous prognostic signs. The value of the morphology of the regional lymph node paracortex in assessing the criteria of host resistance in association with gastric carcinoma is emphasized.     

Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer

The location, frequency, and spread of metastases to the mediastinal lymph nodes were examined in 124 patients with histologically proven N2 disease who underwent pulmonary resection and total lymph node resection. There were one-level metastases in 47 percent of cases, two-level metastases in 29 percent, three-level in 12 percent, and 12 percent had four or more levels of metastases. Nodal metastases to the lower mediastinum from upper lobe cancer were frequently observed as were metastases of lower lobe cancer to the upper mediastinum. The frequency of the latter was higher than that of the former. About one third of squamous cell carcinoma and adenocarcinoma in the right upper lobe produced nodal metastases in the lower mediastinum. In addition, there were often skip metastases to the nonregional parts of the mediastinum without regional nodal involvement in the mediastinum. From the results of the present study, it appears that extensive mediastinal dissection should be recommended in surgery for lung cancer irrespective of the location of the primary tumor.     

Clinical significance of the number of retrieved lymph nodes in early gastric cancer with submucosal invasion

The prognosis of early gastric cancer (EGC) with submucosal invasion is favorable; however, several cases of recurrence have been reported even after curative gastrectomy. This study aimed to investigate risk factors and evaluate the clinical significance of the number of retrieved lymph nodes (LNs) in EGC with submucosal invasion. We retrospectively analyzed the data of 443 patients with gastric cancer with submucosal invasion after curative gastrectomy for recurrent risk factors. Recurrence was observed in 22 of the 443 gastric cancer patients with submucosal invasion. In the univariate analysis, the risk factors for recurrence were the number of retrieved LNs ≤ 25 and node metastasis. In the multivariate analysis, retrieved LNs ≤ 25 (hazard ratio [HR] = 5.754, P-value = .001) and node metastasis (HR = 3.031, P-value = .029) were independent risk factors for recurrence after curative gastrectomy. Body mass index was related to retrieved LNs ≤ 25 in univariate and multivariate analyses (HR = .510, P = .002). The number of retrieved LNs and node metastases were independent risk factors for EGC with submucosal invasion. For EGC with submucosal invasion, retrieved LNs > 25 are necessary for appropriate diagnosis and treatment.     

P-糖蛋白在贲门癌原发灶及其淋巴结转移灶的表达及意义

目的探讨P-糖蛋白(P-gp)在贲门癌原发灶及其淋巴结转移灶的表达差异,并分析与临床病理学因素的关系。方法收集30例经病理确诊的贲门癌原发灶、淋巴结转移灶及对应癌旁正常组织,采用免疫组织化学二步法检测3组标本的P-gp表达。结果 (1)P-gp在淋巴结转移灶、原发灶及癌旁正常组织的阳性表达率分别为66.7%、40%和16.7%,P-gp在淋巴结转移灶中的表达高于原发灶,原发灶高于正常组织(P<0.05)。(2)P-gp在贲门癌原发灶的表达与性别、年龄、浸润深度及分化程度均无关(P<0.05);在淋巴结转移灶的表达与性别、年龄、浸润深度无关,与分化程度有关(P<0.05)。结论 P-gp参与贲门癌肿瘤细胞的原发性多药耐药;淋巴结转移灶与原发灶的肿瘤细胞间存在多药耐药异质性。     

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival

AIM:To assess whether differential expression of caspase-3 in paired metastatic lymph nodes(LNs)is prognostic of survival in patients with resectable esophageal squamous cell carcinoma(ESCC).METHODS:Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays.The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.RESULTS:The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors(P<0.001).Caspase-3 expression in the primary tumors was associated with longer median survival(23 mo vs21 mo,P=0.033),whereas higher expression in paired metastatic LNs was associated with shorter median survival(20 mo vs 22 mo,P=0.043).Multivariate analysis showed that both were independent prognostic factors.CONCLUSION:Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis.Protein expression in metastatic tumors may be a biomarker prognostic of survival.     

Impact of age on the prognostic value of number of lymph nodes retrieved in patients with stage II colorectal cancer

Purpose

A small number of lymph nodes retrieved (NLNR) is a known risk factor in stage II colorectal cancer. NLNR is influenced by age, but little is known about whether the impact of small NLNR on survival differs with age. This retrospective study sought to determine such impact in elderly patients with stage II colorectal cancer.

Methods

We reviewed data for 2100 patients with stage II colorectal cancer who underwent surgery without adjuvant chemotherapy between January 1997 and December 2003. The optimal cutoff value of NLNR for survival was determined, and the impact of small NLNR on survival was analyzed. The association between age and NLNR was evaluated. The relation between age and risk of small NLNR with respect to survival was then assessed to determine the impact of small NLNR on elderly patients’ survival.

Results

The optimal cutoff value of NLNR was determined as 6. The small NLNR group (SNG) showed significantly worse prognosis than the large NLNR group (LNG) (p?<?0.001). Age, surgical method, and scope of lymph node dissection were significantly associated with NLNR. A potential interaction was noted between age and risk of small NLNR in relation to relapse-free survival (RFS). Five-year RFS was significantly worse in SNG than in LNG for elderly patients (41.7 and 76.4 %, respectively; p?<?0.001) but not for non-elderly patients (75.9 and 84.6 %, respectively; p?=?0.083).

Conclusions

NLNR <6 was identified to be an important prognostic factor for elderly patients with stage II colorectal cancer.

     

Clinicopathologic factors correlated with number of metastatic lymph nodes in oesophageal cancer

BACKGROUND: The number of metastatic lymph nodes is applied to the staging system of gastric cancer and colorectal cancer. However, it has not been evaluated in oesophageal cancer. PATIENTS AND METHODS: Of 258 patients with primary squamous cell carcinoma of the thoracic oesophagus between February 1981 and December 1999, 160 underwent three-field oesophagectomy with a curative intent. Clinicopathologic characteristics of those 160 patients were retrospectively investigated according to the number of metastatic lymph nodes. RESULTS: Seventy-eight patients had no lymph node metastases and 82 (51.3%) had lymph node metastases; 51 [31.9%)] had between 1 and 4 positive lymph nodes, and 31 (19.4%) had > or =5. The number of metastatic lymph nodes was significantly correlated with tumour size, macroscopic classification, histological differentiation, pT, pN, and vessel invasions. Multivariate analysis showed that lymph vessel invasion (relative risk 12.6), histological differentiation (relative risk 4.2), and tumour size (relative risk 3.8) were independent factors correlated with number of metastatic lymph nodes. The number of metastatic lymph nodes was also well correlated with the Japanese nodal level and TNM stage, respectively (p<0.001). The 5-year disease-specific survival rate according to the number of positive lymph nodes was 90% for patients without lymph node metastases, 52.2% with 1-4, and 28.9% with > or =5, respectively, p<0. 0001; 0 vs 1-4, p<0.05; 1-4 vs > or =5). CONCLUSION: The number of positive lymph nodes is well correlated with tumour progression and provides a useful prognostic indicator after oesophagectomy for oesophageal cancer.     

淋巴结转移数、转移度及转移区域数与中晚期胸段食管鳞癌预后的关系

目的探讨淋巴结转移个数、转移度及转移区域数与中晚期胸段食管鳞癌（ESCC）预后的关系。方法回顾性分析2002年1月～2006年12月在我院行胸段ESCC根治术的339例中晚期胸段ESCC患者的临床资料。结果全组共清除淋巴结4767枚,淋巴结转移445枚,淋巴结转移度9．34％,每例平均清除淋巴结14．06枚;339例中晚期胸段ESCC的1、3、5a生存率分别为80．49％、41．94％、23．12％,其中有淋巴结转移与无淋巴结转移的1、3、5a生存率差异显著（P〈0．01）;淋巴结转移数量、转移度及转移区域数与 晚期胸段ESCC的预后呈负相关（P〈0．01）。结论淋巴结转移数量、转移度及转移区域数是影响中晚期胸段ESCC预后的重要因素。     

Histological evaluation for chemotherapeutic responses of metastatic lymph nodes in gastric cancer

AIM: To investigate the effect of preoperative chemotherapy (pre-CTx) for metastatic lymph nodes (MLNs) of gastric cancer (GC).METHODS: A retrospective cohort of patients with advanced GC, who underwent pre-CTx followed by gastrectomy, was reviewed. The histological tumor regression grade (TRG), which considered the percentage of residual cancer in the visible tumor bed, was applied to primary tumors and individual MLNs: G1a (complete response), G1b (< 10%), G2 (10%-50%) and G3 (> 50%). The clinical response to pre-CTx was retrospectively evaluated using only MLNs information, and we compared the histological and clinical evaluations of MLNs.RESULTS: Twenty-eight patients were enrolled. A total of 438 MLNs were retrieved, and 22 (5%), 48 (11%), 63 (14%) and 305 (70%) LNs were assigned as G1a, G1b, G2 and G3, respectively. Stratification of the residual MLNs based on the TRGs was as follows: 28 G1b MLNs (9%), 48 G2 MLNs (15%), and 253 G3 MLNs (76%) in the D1 region; 20 (23%), 15 (17%), and 52 (60%) in the D2 region, respectively. However, no significant correlation was found between TRGs in MLNs and clinical response in the subgroup for which evaluation of clinical response was available.CONCLUSION: Pre-CTx does not provide any outstanding histological benefit for MLNs, and an appropriate D2 lymphadenectomy should routinely be performed to offer the chance of curative resection.     

胃黏膜内癌淋巴结微转移的临床意义

目的：研究胃黏膜内癌淋巴结微转移的发生率、病理学特征及其临床意义.方法：胃黏膜内癌患者84例手术切除淋巴结2526枚进行连续超薄切片,分别进行HE染色及抗Cytokeratin(CK；CAM5.2)免疫组化研究,并与临床病理资料进行对比分析.结果：在84例中16例患者具有淋巴结受累(19%)；2526枚淋巴结中45枚淋巴结受累(1.8%；45/2526),显著高于HE染色的1.2% (1/84；P＜0.05),淋巴结微转移率为18% (15/84).尽管没有显著统计学差异,微转移在大于1.0cm的肿瘤(15/72；21%)较小于或等于1.0cm的肿瘤(1/12；8%)更为多见(P=0.307).大于2.0cm的肿瘤,淋巴结的微转移均为淋巴结内多发散在或聚集状态的肿瘤细胞.结论：胃黏膜内癌具有较高的淋巴结微转移率,内镜下黏膜切除术不宜用于直径大于1.0cm的胃黏膜内癌.     

Anatomical location of metastatic lymph nodes: an indispensable prognostic factor for gastric cancer patients who underwent curative resection

Background: Although the numeric-based lymph node (LN) staging was widely used in the worldwide, it did not represent the anatomical location of metastatic lymph nodes (MLNs) and not reflect extent of LN dissection. Therefore, in the present study, we investigated whether the anatomical location of MLNs was still necessary to evaluate the prognosis of node-positive gastric cancer (GC) patients.

Methods: We reviewed 1451 GC patients who underwent radical gastrectomy in our institution between January 1986 and January 2008. All patients were reclassified into several groups according to the anatomical location of MLNs and the number of MLNs. The prognostic differences between different patient groups were compared and clinicopathologic features were analyzed.

Results: In the present study, both anatomical location of MLNs and the number of MLNs were identified as the independent prognostic factors (p?p?p?p?Conclusion: The anatomical location of MLNs was an important factor influencing the prognostic outcome of GC patients. To provide more accurate prognostic information for GC patients, the anatomical location of MLNs should not be ignored.     

Correlation of tumor-positive ratio and number of perigastric lymph nodes with prognosis of patients with surgically-removed gastric carcinoma

AIM: To evaluate the tumor-positive ratio and number of perigastric lymph nodes as prognostic factors of gastric carcinoma in surgically-treated patients. METHODS: The postoperative survival of 169 patients with gastric cancer who were performed D2 curative gastrectomy was analyzed with regard to its lymph node metastasis ratio and number. Meanwhile correlation of tumor-positive ratio and number of perigastric lymph nodes with pathological parameters of these patients was studied. RESULTS: The overall 5-year survival rate of all the patients studied was 29.6%. The 5-year cumulative survival rate in patients with 1%-20% and more than 20% of tumor-positive lymph nodes was 70.6% and 12.0% respectively, and 46.6% and 17.4% in those with 1-5 and more than 5 of tumor-positive lymph nodes respectively, which were significantly decreased with the increment of involved lymph nodes assessed by either numbers or ratio (P<0.05). Multiple stepwise regression analysis showed that both the positive ratio and number of tumor-involved lymph nodes were sensitive prognostic factors in these surgically-treated patients, which were also significantly correlated with tumor size and depth of submucosal invasion (P<0.05). CONCLUSION: Tumor-positive ratio and number of perigastric lymph nodes are associated with cancer progression and five-year survival rate, and may serve as valuable prognostic factors of gastric cancer in surgically-treated patients.     

贲门癌淋巴结微转移的检测及意义

目的观察常规病理学检查无淋巴结转移的贲门癌淋巴结的微转移情况,并探讨其临床意义。方法采用免疫组化SP法,用细胞角蛋白19（CK19）单抗和CD44v6单抗检测48例贲门癌患者常规病理学检查阴性的323枚淋巴结的微转移情况。结果本组9例14枚淋巴结发现微转移。淋巴结微转移与贲门癌患者年龄、性别及肿瘤直径、浸润深度、分化程度无关（P均〉0．05）,与贲门癌的Lauren分型有关（P〈0．05）。45例随访患者中,有淋巴结微转移者3、5年生存率明显低于无淋巴结微转移者（P均〈0．01）。结论常规病理学检查无淋巴结转移的贲门癌患者淋巴结常存在微转移;淋巴结微转移的检测有助于贲门癌患者的预后判断。     

Impact of the number of examined lymph nodes on outcomes in patients with lymph node-negative gallbladder carcinoma

AIM To determine whether the number of examined lymph nodes(LNs) is correlated with the overall survival of gallbladder carcinoma(GBC) patients. METHODS Patients were collected from the Surveillance Epidemiology and End Results database(2004-2013) and categorized by the number of LNs into six groups: 1 LN, 2 LNs, 3 LNs, 4 LNs, 5 LNs, and ≥ 6 LNs. Survival curves for overall survival were plotted with a KaplanMeier analysis. The log-rank test was used for univariate comparisons.RESULTS In a cohort of 893 patients, the median number of examined LNs was two for the entire cohort. The survival for the 1 LN group was significantly poorer than those of the stage Ⅰ and Ⅱ disease groups and for the entire cohort. By dichotomizing the number of LNs from 1 to 6, we found that the minimum number of LNs that should be examined was four for stage Ⅰ, four or five for stage Ⅱ, and six for stage ⅢA disease. Therefore, for the entire cohort, the number of examined LNs should be at least six, which is exactly consistent with the American Joint Committee on Cancer criteria.CONCLUSION The examination of higher numbers of LNs is associated with improved survival after resection surgery for N0 GBC. The guidelines for GBC surgery, which recommend that six LNs be examined at least, are statistically valid and should be applied in clinical practice widely.     

Anatomical location and number of metastatic lymph nodes for prognosis of non-small cell lung cancer

BackgroundThe nodal classification of lung cancer is determined by the anatomical location of metastatic lymph nodes (mLNs). However, prognosis can be heterogeneous at the same nodal stage, and the current classification system requires improvement. Therefore, we investigated the correlation between the number of mLNs and prognosis in patients with non-small cell lung cancer.MethodsUsing a multicenter database in Japan, we retrospectively reviewed the records of patients who underwent complete resection for lung cancer between 2010 and 2016. Kaplan-Meier curves were used to determine recurrence-free and overall survival. Multivariate analyses were performed using the Cox proportional hazards model.ResultsWe included 1,567 patients in this study. We could show a statistically significant difference in recurrence-free survival between pN2 patients with 1 mLN and pN2 patients with ≥2 mLNs (P=0.016). Patients with a combination of pN1 (≥4 mLNs) plus pN2 (1 mLN) had a poorer prognosis than pN1 patients (1-3 mLNs) (P=0.061) and a better prognosis than pN2 patients (≥2 mLNs) patients (P=0.007). Multivariate analysis showed that the number of mLNs was independently associated with cancer recurrence in patients with pN1 and pN2 disease (P=0.034 and 0.018, respectively).ConclusionsNodal classification that combines anatomical location and the number of mLNs may predict prognosis more accurately than the current classification system. Our study provides the concept that supports the subdivision of nodal classification in the upcoming revision of the tumor, node, and metastasis staging system.     

Effects of preoperative chemotherapy on metastatic lymph nodes in esophageal squamous cell carcinoma

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.