The range of tumor extension should have precedence over the location of the deepest tumor center in determining the regional lymph node grouping for widely extending esophageal carcinomas

BACKGROUND: The Japanese Guide Lines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus (9th edn) give precedence to the location of the deepest tumor center rather than the range of tumor extension when determining regional lymph node grouping. We evaluated the validity of this recommendation. METHODS: The subjects were 49 patients with carcinomas of the distal thoracic esophagus and cardia who had undergone esophagectomy with three-field lymph node dissection. We measured variables defining tumor location, such as the distance from the esophagogastric junction (EGJ) to the proximal margin of the tumor (DJP), the distance from the EGJ to the distal margin of the tumor (DJD), and the distance from the EGJ to the deepest tumor center (DJC). To examine the relation of tumor location to lymph node metastasis in the proximal direction, the patients were divided into two groups according to the presence (14 patients) or absence (35 patients) of middle-upper mediastinal and/or cervical lymph node metastases. These two groups were compared with respect to the above variables. To analyze lymph node metastasis in the distal direction, the patients were also divided into two groups according to the presence (12 patients) or absence (37 patients) of distant abdominal lymph node metastases. These two groups were similarly compared with respect to the above variables. RESULTS: DJP was significantly longer in the patients with middle-upper mediastinal and/or cervical lymph node metastases than in those without such metastases. Multiple logistic regression analysis showed that the DJP was a better predictor of middle-upper mediastinal and/or cervical lymph node metastases than was the DJC. The DJD was significantly longer in the patients with distant abdominal lymph node metastases. Multiple logistic regression analysis also showed that the DJD was a better predictor of distant abdominal lymph node metastases than was the DJC. CONCLUSIONS: The range of tumor extension is a more reliable predictor of the risk of distant lymph node metastases than is the location of the deepest tumor center in esophageal carcinoma.     

胸段食管癌喉返神经旁淋巴结转移的风险模型构建及预测能力的初步验证

目的:探讨影响胸段食管癌喉返神经旁淋巴结转移的危险因素,构建模型并检验其预测效能。方法:收集2014年1月至2017年1月我院收治的89例患者为造模组,根据术后病理结果,将患者分为转移组与未转移组,分析可能影响喉返神经旁淋巴结转移发生的相关因素。根据危险因素权重,构建风险模型。同时,连续性收集2017年2月至2018年12月的47例患者资料,验证模型的预测效能。结果:Logistic回归分析发现,肿瘤位置、分化程度、浸润深度、淋巴结SUV值、CT下淋巴结征象是影响喉返神经旁淋巴结转移发生的独立性危险因素（P＜0.05）。根据Logistic回归分析,可得回归方程:P预测=-0.754－1.347X1－1.361X2＋1.282X3＋3.380X4＋1.912X5,X1:肿瘤位置（1=上段,2=中段,3=下段）、X2:分化程度（1=低分化,2=中分化,3=高分化）、X3:浸润深度（1=T1,2=T2,3=T3,4=T4）、X4:淋巴结SUV值（1=SUVmax≥2.5,2=SUVmax＜2.5）、X5:CT下淋巴结征象（1=阴性,2=阳性）。ROC曲线的Youden指数最大值为0.710,截断值为0.662,敏感性为70.9%,特异性为99.1%,曲线下面积为0.918。将验证组患者各因素带入预测模型,检验该模型预测效能,结果发现,ROC曲线下面积为0.79,Hosmer-Lemeshow拟合优度检验显示,χ2=1.52,P=0.93。模型拟合效度好,预测价值高。结论:影响胸段食管癌发生喉返神经旁淋巴结转移的高危因素多,临床应进行及时有效评估。本研究构建的预测模型有较好的评估效能,有一定的临床应用价值。     

c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases.

PURPOSE: Both c-MET and vascular endothelial growth factor (VEGF)-C expression are important factors in primary carcinoma progression. We hypothesized that overexpression of c-MET and/or VEGF-C mRNA in primary colorectal cancer (CRC) can predict tumor invasion and regional metastasis. EXPERIMENTAL DESIGN: The level of c-MET and VEGF-C mRNA expression was assessed using a quantitative RT-RealTime PCR assay on early stage primary CRC tumors (n = 36). RESULTS: The c-MET mRNA copy number ranged from 1.18 x 10(2) to 1.11 x 10(6) copies (median 5.17 x 10(4)) per 250 ng of RNA from CRC specimens. c-MET mRNA copies in CRC specimens was significantly higher than that from normal colon mucosal epithelium (P = 0.0001). c-MET mRNA copies significantly correlated with the depth of invasion: T(1) versus T(2), P = 0.007; T(1) versus T(3)/T(4), P = 0.0001; T(1) versus T(2) versus T(3)/T(4), P = 0.0005; and T(1)/T(2) versus T(3)/T(4), P = 0.011. c-MET copy number in primary CRC of N(1)/N(2) staged patients was significantly higher than N(0) cases (P < 0.03). Expression levels of c-MET mRNA were verified with immunohistochemistry analysis of c-MET protein expression in CRC specimens and normal mucosal epithelium. The VEGF-C mRNA copies of primary CRC assessed ranged from 0 to 1.65 x 10(5) copies (median 580). Although VEGF-C mRNA copies in CRC primary tumors were significantly higher than normal colon mucosal epithelium (P = 0.0008), it did not correlate with any major clinicopathological parameters of CRC. CONCLUSIONS: This study indicates c-MET mRNA overexpression in primary CRC may be an important prognostic marker for early stage invasion and regional disease metastasis.     

子宫内膜癌淋巴转移的危险因素分析

目的 子宫内膜癌可通过淋巴转移、直接蔓延、血行转移途径转移,其中淋巴转移为主要途径.早期子宫内膜癌初始治疗时术中是否行淋巴结切除仍存在争议.本研究拟通过回顾性分析子宫内膜癌盆、腹腔淋巴结转移的危险因素,为术中是否行淋巴结切除提供依据.方法 对2008-01-01-2015-05-01在中国医科大学附属盛京医院住院的818例子宫内膜癌患者的临床资料进行回顾性分析.选取年龄、病理类型、分化程度、肌层浸润深度、CA125水平等可能与发生淋巴转移的相关危险因素,并通过SPSS 17.0软件和Logistic回归模型进行统计分析.结果 818例子宫内膜癌患者中淋巴结转移88例(10.76％),其中盆腔淋巴结转移85例(10.39％),腹主动脉旁淋巴结转移15例(8.72％).单因素分析结果显示子宫内膜癌淋巴结转移与肿瘤部位、分化程度、病理类型、肌层浸润深度、宫颈浸润、附件转移、宫旁转移、CA125、雌激素受体、孕激素受体、盆腔部位转移、合并子宫肌瘤相关,P值均＜0.05.多因素分析结果显示,分化程度、病理类型、肌层浸润、附件转移、CA125水平升高是子宫内膜癌淋巴结转移的独立危险因素,P值均＜0.05.结论 子宫内膜癌术中应充分考虑分化程度、病理类型、肌层浸润、附件转移、CA125水平等危险因素,以决定是否行淋巴切除术.     

Macroscopic extranodal invasion is a risk factor for tumor recurrence in papillary thyroid cancer

Papillary thyroid cancer patients, upon whom curative operation was performed, were investigated to clarify whether or not macroscopic extranodal invasion is a risk factor for recurrence. They were divided into three groups: group A, patients whose primary tumor showed extrathyroidal invasion (n=31); group B, those whose metastatic lymph nodes showed extranodal invasion (n=6); group C, those who showed both extrathyroidal and extranodal invasion (n=9). Recurrence was significantly higher in groups B and C than in group A (P<0.05).It was concluded that macroscopic extranodal invasion to the adjacent structures was a risk factor for recurrence in patients with papillary thyroid cancer.     

The role of pelvic lymph node dissection as a predictive and prognostic factor in bladder cancer

The aim of this study was to evaluate the value of pelvic lymph node dissection (PLND) performed as a separate procedure in a consecutive Danish bladder cancer cohort and also to analyse if the number of lymph nodes excised had an impact on outcome. From 1992 to 1998, 339 cystectomy candidates were retrospectively reviewed. Based on a preoperative PLND, 248 patients (10% N+) underwent radical cystectomy and 91 (87% N+) underwent radio- or chemotherapy. The median follow-up was 6.3 years. PLND was able to separate N+ from N0 patients with a false-negative rate of 3% compared with the following cystectomy. Lymph node-positive patients treated with cystectomy (n=24) all died from their bladder cancer. Therefore, accurate pathological N classification before the treatment decision seems worthwhile. The median number of lymph nodes excised was six and the number of lymph nodes had an independent prognostic impact on survival. This underlines the need for guidelines for surgical lymphadenectomy and the pathological assessment of lymph nodes in bladder cancer.     

胸部食管癌转移淋巴结数与预后的临床研究

目的 探讨胸部食管癌转移淋巴结的个数与预后的关系。方法 采用颈、胸、腹三切口施行胸部食管癌手术１１２例,同时施行三区域淋巴结清扫。选择９个可能对食管癌切除术后预后产生影响的特征性临床因素,通过Ｃｏｘ比例风险模型,利用累计生存率对食管癌切除术后患者进行预后多因素分析。结果 本组总５年生存率为５８．４％,其中无淋巴结转移组（Ａ组）为８８．４％、转移淋巴结１～３枚组（Ｂ组）为５０．８％,转移≥４枚组（Ｃ     

胸段食管癌淋巴结转移规律与放疗意义探讨

目的 了解胸段食管癌淋巴结转移规律，探讨胸段食管癌放疗临床靶区的设计。方法 对首程治疗行颈、胸、腹3个野根治术的胸段食管鳞癌患者621例，标记各部位清扫的淋巴结分别送检，进行临床病理资料分析，了解淋巴结转移规律，为食管癌放疗临床靶区的设计提供理论依据。结果 胸上、中、下段食管癌颈部淋巴结转移率分别为42．9％、27．9％和7．9％，上纵隔的分别为31．2％、24．0％和10．1％，中纵隔的分别为14．3％、29．7％和33．7％，下纵隔的分别为1．3％、4．0％和19．1％，腹部的分别为11．7％、25．1％和55．1％。胸部各段食管癌淋巴结转移部位比较差异有统计学意义（P〈0．05）。病变长度愈长、肿瘤分化越低、肿瘤浸润越深食管癌淋巴结转移率也愈高（P〈0．05）。结论 胸上段食管癌淋巴结转移以颈段食管旁、锁骨上、上中纵隔转移多见，胸中段食管癌淋巴结转移具有明显的上下双向转移和跳跃性转移特点，胸下段食管癌淋巴结转移以腹部、中下纵隔转移多见。建议胸上段食管癌临床靶区的范围上界包括颈段食管旁及锁骨上、下界包括隆突下的淋巴结引流区，胸下段食管癌临床靶区的范围上界至隆突水平、下界包括胃左血管旁的淋巴结引流区，胸中段食管癌临床靶区的范围应根据具体情况设定。     

Vascular invasion by tumor in the absence of regional lymph node metastases in patients with locally advanced non-small cell lung cancer

The study included 45 patients radically operated for locally advanced (T3, T4) non-small cell lung cancer (NSCLC), free from metastasis to the regional lymph nodes. The histological subtypes were: squamous cell cancer (40; 89%), adenocarcinoma (4; 6%) and large-cell lung cancer (1; 2%). Pathomorphological stage: IIb (p T3N0M0)--35 (78%); IIIb (p T4N0M0)--10 (22%). Blood vessel invasion: tumor T3--8 (23%); T4--2 (20%). Lymph vessel invasion: T3--9 (9%) and T4--2 (2%) (p(0.05). In total, tumor invasion was reported in 16 patients: T3--12 (34%) and T4--4 (40%) (p(0.05). There was no significant difference in survival among IIb or IIIb stage NSCLC patients. None of the cases of blood vessel invasion survived 5 years after surgery. Five-year survival in patients without vascular invasion was 55% (p(001). Tumor invasion of blood and lymph vessels is associated with high probability of tumor dissemination and poor prognosis.     

Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer

To search for reliable predictors for lymph node metastasis, we immunohistochemically analyzed surgically resected gastric cancer specimens that showed invasion of submucosa (sm) and muscularis propria (mp) of the tumor. The analysis investigated cathepsin D and Ki-67 expression in 136 specimens that were divided into an sm1/sm2 group and an sm3/mp group. In sm1/sm2 group, the incidence of lymph node metastases was significantly higher in tumors with high Ki-67 labeling index (LI) (44%) than in those with low Ki-67 LI (0%). In sm3/mp group, the incidence of lymph node metastases was significantly higher in cathepsin D-positive (56%) and high Ki-67 LI tumors (64%) than in cathepsin D-negative (33%) and low Ki-67 LI (33%). Combined analysis of cathesin D expression and Ki-67 LI correlated strongly with lymph node metastases. No lesions with cathepsin D-negative expression and low Ki-67 LI had lymph node metastases in either group. Cathepsin D and Ki-67 expression may be useful predictors for lymph node metastases in gastric cancer with sm and mp invasion. As predictors, they can identify lesions without lymph node metastases and indicate lesions not needing additional treatment after endoscopic mucosal resection and laparoscopic gastrectomy.     

Automated quantitative analysis of E-cadherin expression in lymph node metastases is predictive of survival in invasive ductal breast cancer.

PURPOSE: The tumor suppressor adhesion molecule E-cadherin is believed to have an anti-invasive role in breast cancer. Lymph node involvement is the best prognostic marker known, yet there is variability in outcome among node-positive patients. We investigated the relationship between E-cadherin expression in primary invasive ductal tumors and corresponding nodal metastases, and determined the prognostic value of E-cadherin expression in node-positive breast cancer. EXPERIMENTAL DESIGN: Membrane E-cadherin expression was studied by immunohistochemical staining of tissue microarrays with fluorescent-labeled antibodies. An objective method of automated quantitative analysis (AQUA) was used. AQUA uses cytokeratin to define pixels as breast cancer (tumor mask) within the array spot, and measures E-cadherin expression using a Cy5-conjugated antibody within the mask. RESULTS: We employed a tissue microarray containing 207 primary and matched nodal metastases suitable for AQUA analysis. There was no significant difference in mean staining intensity between the primary and nodal specimens (P = 0.8). A scattergram was generated which identified a subset of patients (25%) with high E-cadherin expression in nodal metastases, and this top quartile had improved survival (P = 0.028). On univariate analysis, increased E-cadherin expression in nodal metastases was strongly associated with improved survival (P = 0.007), whereas expression in primary tumors was not (P = 0.13). On multivariate analysis, nodal E-cadherin expression retained its independent association with survival, as did tumor size and HER2/neu status. CONCLUSIONS: Strong E-cadherin expression in lymph node metastases was highly predictive of improved survival. This suggests that expression of adhesion molecules at metastatic sites portends less aggressive tumor behavior.     

Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN

Aims

A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive.

Methods

A Medline search was conducted that ultimately identified 56 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random-effects model was used to combine odds ratios to determine the strength of the associations.

Findings

The 8 individual characteristics found to be significantly associated with the highest likelihood (odds ratio >2) of NSN metastases are SLN metastases >2 mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2 cm, ratio of positive sentinel nodes >50% and lymphovascular invasion in the primary tumour. The histological method of detection, which is associated with the size of metastases, had a correspondingly high odds ratio.

Conclusions

We identified 8 factors predictive of NSN metastases that should be recorded and evaluated routinely in SLN databases. These factors should be included in a predictive model that is generally applicable among different populations.     

Tumor differentiation is not a risk factor for lymph node metastasis in elderly patients with early gastric cancer

BackgroundThe aim of this study was to identify risk factors for lymph node metastasis in elderly patients (70 years or more) with early gastric cancer.MethodsWe reviewed the prospectively collected database of 6893 patients with early gastric cancer who had undergone curative gastrectomy in 3 tertiary cancer centers between January 2003 and December 2009 in Korea. Patients were sorted into 4 groups according to age: less than 50, fifties, sixties, and 70 years or more. Risk factors for lymph node metastasis in early gastric cancer were analyzed.ResultsOne thousand and thirty five patients (15.0%) were 70 years or more. As age increased, the frequency of large differentiated tumor, lymphatic and submucosa invasion increased. Old age was associated with a lower risk for lymph node metastasis in patients with early gastric cancer (Odds ratio [OR], OR, 0.622; 95% CI, 0.5466–0.830, P = 0.010). Ulceration or differentiation of tumor was not associated with lymph node metastasis in elderly patients with early gastric cancer.ConclusionsElderly patients with undifferentiated type histology early gastric cancer without other risk factors for lymph node metastasis may be candidates for endoscopic resection.     

阴性淋巴结数目对胸段食管癌患者预后的影响

目的:探讨胸段食管癌患者标准淋巴结清扫术中阴性淋巴结数目对患者预后的影响。方法:回顾性分析2000～2006年,汕头市中心医院239例食管癌患者的性别、年龄、肿瘤定位、浸润深度、病理组织分化程度、类型以及阴、阳性淋巴结数目,通过Kaplan-Meier曲线和Cox多因素回归模型,评估上述临床病理参数等与患者生存期之间的相关性。结果:全组患者平均5年生存率44.1%。单因素分析结果显示,阳性淋巴结数目及阴性淋巴结数目对患者5年生存率有显著影响(P0.05)。阴性淋巴结数目≥4的患者,5年生存率(49.1%)明显高于阴性淋巴结数目4的患者(31.5%)(x~2=6.042,P=0.014)。Cox多因素回归分析显示,阳性淋巴结数目(P=0.000,HR=1.370,95%CI=1.204～1.559)及阴性淋巴结数目(P=0.046,HR=0.955,95%CI=0.913～0.999)均可作为影响患者预后的独立影响因素(P0.05)。结论:阴性淋巴结数目是胸段食管癌患者预后的独立影响因素,在今后的食管癌分期标准中可用于改进淋巴结分期。     

Prognostic significance of the number of negative lymph node on the survival of patients with thoracic esophageal cancer

目的:探讨胸段食管癌患者标准淋巴结清扫术中阴性淋巴结数目对患者预后的影响.方法:回顾性分析2000～2006年,汕头市中心医院239例食管癌患者的性别、年龄、肿瘤定位、浸润深度、病理组织分化程度、类型以及阴、阳性淋巴结数目,通过Kaplan-Meier曲线和Cox多因素回归模型,评估上述临床病理参数等与患者生存期之间的相关性.结果:全组患者平均5年生存率44.1％.单因素分析结果显示,阳性淋巴结数目及阴性淋巴结数目对患者5年生存率有显著影响(P＜0.05).阴性淋巴结数目≥4的患者,5年生存率(49.1％)明显高于阴性淋巴结数目＜4的患者(31.5％)(x2=6.042,P=0.014).Cox多因素回归分析显示,阳性淋巴结数目(P=0.000,HR=1.370,95％CI=1.204～1.559)及阴性淋巴结数目(P=0.046,HR=0.955,95％CI=0.913～0.999)均可作为影响患者预后的独立影响因素(P＜0.05).结论:阴性淋巴结数目是胸段食管癌患者预后的独立影响因素,在今后的食管癌分期标准中可用于改进淋巴结分期.     

Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti‐NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.