Retropharyngeal lymph node metastasis in oral cancer. Systematic review and survival analysis

IntroductionMetastasis to retropharyngeal lymph nodes (RPLN) from oral squamous cell carcinoma is rare and associated with poor outcomes. The poor prognosis of RPLN is multifactorial and includes the clinicopathological aggressiveness of the primary disease and the late presentation. The aim of this systematic review is to assess the evidence on RPLN in patients diagnosed with oral squamous cell carcinoma (OSCC), the quality of the diagnostic modalities and the available treatment options. We aimed to analyse the overall survival of these patients diagnosed with RPLN.MethodsA systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The initial literature search generated 289 articles. A total of 11 papers satisfied our criteria. Eight papers provided enough data to perform survival analysis and 3 papers compared the diagnostic modalities used in the detection of RPLN.ResultsA total of 73 OSCC patients diagnosed with RPLN metastasis were identified. The most common primary tumour subsites included the tongue (20), buccal mucosa (15) and gingiva (11). The cumulative 5-year OS rate was 17.8% while the 2-year overall survival was 35.9%.ConclusionThe presence of nodal metastasis is an independent prognostic factor in head and neck cancer. In this study, RPLN metastasis had a poorer prognosis (5 years overall survival is 17.8%) when compared to the survival rate of oral cancer without RPLN metastasis (5 years overall survival is 40%). There was no statistically significant difference between the overall survival in primary RPLN metastasis and recurrent RPLN disease.     

US and CT evaluation of cervical lymph node metastasis from oral cancer

A comparison was made of clinical diagnosis by ultrasound (US) and CT examination in 52 patients who had undergone radical neck dissection. The site, size, depth and other patterns concerning the nodes which could not be detected by physical examination was examined. US and CT examination proved superior to conventional clinical examination in detecting metastatic nodes. US and CT revealed that the disease stage in nine necks had increased from N1 to N2b and in seven of 11 necks from N0 to N positive. The characteristic features of US and CT diagnosis of metastatic lymph nodes were elucidated. Specifically, the diagnosis of cervical metastatic nodes by a combination of US and CT was found to be the most reliable method for detection of subclinical lymph nodes.     

The relative cost of sentinel lymph node biopsy in early oral cancer

IntroductionThe European Sentinel Node (SENT) trial addressed the question of the clinically lymph node negative (cN0) neck in early oral squamous cell carcinoma (OSCC). Apart from reducing neck dissection numbers, sentinel lymph node biopsy (SLNB) may reduce treatment cost. Using a treatment model derived from SENT trial information, estimates were produced of relative treatment costs between patients managed through a traditional surgical or SLNB pathway.MethodsThe model created two management approaches, the traditional surgical pathway and SLNB pathway. Using SENT trial data regarding the proportion of patients with positive, negative and false negative SLNB's a relative cost ratio (RCR) for 100 hypothetical patients passing down each pathway was generated.ResultsFrom a cohort of 481 patients, 25% had a positive SLNB, 75% a negative result and 2.5% a false negative result. Treatment of 100 hypothetical patients using the SLNB pathway is 0.35–0.60 the cost of treating the same cohort using traditional surgery techniques. Even if 100% of SLNB's are positive the SLNB approach is 0.91 of the cost of the traditional surgical approach.ConclusionThe SLNB approach appears to be cheaper relative to the traditional surgical approach, especially when extrapolated to 100 hypothetical patients.     

平阳霉素-活性炭纳米微粒行口腔癌淋巴化疗的靶向性评价

目的 观察平阳霉素-活性炭纳米微粒(PYM-CH-NP)经鼠癌周黏膜下给药后,活性药物在体内各组织器官中的分布情况,探讨PYM-CH-NP对淋巴结转移灶的靶向性.方法 采用改良氯胺T法将125I标记平阳霉素(PYM),应用淋巴结高转移癌株U14建立昆明小鼠颈淋巴结转移模型.将360只颈淋巴结转移模型小鼠随机分为PYM-...     

100例cNO舌癌患者隐匿性淋巴结转移部位及相关因素分析

目的分析cN0舌癌患者隐匿性淋巴结转移特点及临床病理因素对隐匿性转移的影响,为选择性颈清扫提供临床依据。方法收集100例cN0舌癌患者资料,分析其隐匿性颈淋巴结转移的特点及原发灶的直径、T分级、浸润深度、生长方式、病理分级、分化程度等对隐匿性转移的影响。结果 100例cN0舌癌隐匿性颈淋巴结转移率为22%,最常见的转移部位是同侧的Ⅱ区,占总转移部位的51.61%（16/31）,其次分别为同侧Ⅰ和Ⅲ区,87.10%（27/31）的隐匿性转移位于以上三个区域。另外,舌癌的直径与隐匿性转移无明显关系（P〉0.05）,而浸润深度、生长方式、病理分级,肿瘤分级和分化程度对其有显著性影响（P〈0.05）,且随着病理分级、分化程度、浸润深度递增,转移率有升高的趋势。结论同侧的Ⅰ、Ⅱ和Ⅲ区是cN0舌癌隐匿性颈淋巴结转移的常见区域,综合考虑原发灶的浸润深度、生长方式、病理分级和分化程度等临床病理因素,对较易发生隐匿性颈淋巴结转移的cN0舌癌患者可行选择性肩胛舌骨肌上清扫术。     

Application of neural networks to the prediction of lymph node metastasis in oral cancer

Neural networks are a new type of computing algorithm. They are especially useful in pattern recognition. In this study we applied neural networks to the prediction of lymph node metastasis of patients with oral cancer. A data set of 1,116 lymph nodes verified histopathologically was used to train and evaluate the neural networks. Various three-layer feed-forward networks with a back-propagation algorithm were employed in this study. Performance of the neural networks was compared with that of radiologists and discriminant analysis (Quantification theory type II). Neural networks had a sensitivity of 80.6% and a specificity of 94.6%. Diagnostic accuracy of the neural networks was 93.6%, which was comparable to those of discriminant analysis and clinical radiologists.     

Expression of vascular endothelial growth factor-C does not predict occult lymph-node metastasis in early oral squamous cell carcinoma

Strong vascular endothelial growth factor-C (VEGF-C) expression has been correlated to occurrence of lymph-node metastases in patients with oral squamous cell carcinoma (OSCC). The incidence of occult lymph-node metastasis remains a decisive factor in the prognosis of patients with early OSCC. The aim of this study was to evaluate VEGF-C expression as a predictor of occult lymph-node metastasis in OSCC. Eighty-seven patients with primary OSCC arising in the tongue or floor of mouth, clinically T1N0M0 or T2N0M0, with (pN+) and without (pN0) occult lymph-node metastases were analyzed for VEGF-C expression by malignant cells. Occult lymph-node metastases (pN+) were detected in 22% of the 64 patients who were submitted to elective neck dissection. No statistically significant difference was found between OSCC with and without occult lymph-node metastasis in regard to VEGF-C immunoexpression by malignant cells and clinicopathologic features. Independently of VEGF-C expression, lymph-node metastasis (pN+) was the most significant prognostic factor for overall survival of patients with OSCC (p=0.030). These findings indicate that isolated VEGF-C expression by malignant cells is not of predictive value for occult lymph-node metastasis in the early stages of OSCC.     

VEGFR—3表达与口腔癌淋巴道转移的关系

目的　了解血管内皮生长因子 (VEGF C)及血管内皮生长因子受体 3(VEGFR 3)在正常口腔黏膜、白斑及鳞癌等组织中的表达规律。方法　采用免疫组化染色及图像分析方法 ,确定VEGFR 3的表达及定量。结果　VEGFR 3主要表达定位在脉管结构 ,在正常及病变上皮组织中也有少量表达。口腔癌VEGF C表达阳性之VEGFR 3染色脉管数目比阴性增多 ,淋巴结转移比无转移增多 (P <0 .0 1) ;而鳞癌比正常黏膜、白斑增多 (P <0 .0 5 ) ;随临床分期或病理分级增高 ,VEGFR 3染色脉管数目有增多趋势 ,但无统计学差异 (P >0 .0 5 )。结论　VEGF C表达的增高 ,通过其受体VEGFR 3导致了淋巴管的增生 ,这种增生在肿瘤情况下很可能导致了淋巴道转移的增加     

Prediction of occult cervical lymph node metastasis in patients with stage I -II squamous cell carcinoma of the oral cavity

The presence of lymph node metastasis is the most important prognostic factor in oral cancer. The purpose of this study was to find useful markers for predicting occult cervical lymph node metastasis in patients with stage I or II squamous cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors and 2 genetic markers to predict late or occult cervical metastasis in 33 patients with stage I and II oral squamous cell carcinoma who underwent partial glossectomy through the mouth without elective neck dissection. In this study, we performed fluorescence in situ hybridization (FISH) with specimens obtained by fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material, to investigate numerical aberration of the gene. Late cervical lymph node metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after treatment of the primary tumor. Factors significantly associated with the development of cervical metastasis were the mode of invasion (p = 0.009), cyclin D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease-free survival from metastatic disease was significantly lower in patients with mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in patients with cyclin D 1 or EGFR gene numerical aberrations than in those without such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our results indicate that patients with stage I - II squamous cell carcinoma of the oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene numerical aberration should be considered a high-risk group for late cervical lymph node metastasis.     

Histopathological and lymphangiogenic parameters in relation to lymph node metastasis in early stage oral squamous cell carcinoma.

PURPOSE: Lymph node metastasis from oral squamous cell carcinoma (SCC) correlates with a poor prognosis. Therefore, accurate assessment of lymph node status is crucial in treatment planning. Furthermore, prediction of delayed neck metastasis (DNM), especially in early stage tumors with a clinically negative (N0) neck, will determine the need for neck dissection or irradiation. In this study, we assess various clinical, histopathological and lymphangiogenic parameters in early stage oral SCC and their association with DNM. MATERIALS AND METHODS: Clinical, histological, and immunohistochemical analyses were undertaken for 29 patients with T1N0M0 or T2N0M0 oral SCC affecting the tongue or floor of mouth and correlated with the development of DNM. RESULTS: Tumor thickness, nuclear pleomorphism, pattern of invasion, and immunohistochemical expression of the lymphangiogenesis-associated molecules VEGFR-3 and VEGF-C were associated with DNM. CONCLUSIONS: Analysis of these parameters may help to identify patients who would benefit from a neck dissection or irradiation by predicting the likelihood of lymph node metastasis.     

早期舌癌浸润深度与颈淋巴结转移的关系

目的:观察早期舌癌浸润深度与颈淋巴结转移的关系。方法:收集行颈淋巴清扫术的早期(T1、T2期)舌癌病例54例,测量原发灶肿瘤浸润深度,同时行颈淋巴结的细胞角蛋白(Cytokeratin,CK)AE1／AE3免疫组化染色,观察颈淋巴结转移与肿瘤浸润深度等临床病理因素的关系。结果:舌癌肿瘤浸润深度为1.0-11.0mm,平均为5.2mm。54例病例中发生颈淋巴转移者22例(40.74％)。Fisher's精确概率检验表明,早期舌癌颈淋巴结转移与肿瘤浸润深度及病理分级密切相关;单因素Logistic回归表明,早期舌癌淋巴结转移与肿瘤浸润深度及病理分级相关;多因素Logistic回归表明早期舌癌淋巴结转移仅与肿瘤浸润深度相关(P<0.01)。T1、T2期舌癌肿瘤浸润深度>4mm者,颈淋巴结转移率(60％)显著高于≤4mm者(5.3％)(P<0.01)。结论:肿瘤浸润深度对评估早期舌癌颈淋巴结转移有重要意义。     

前哨淋巴结活检对早期口腔鳞状细胞癌颈淋巴结转移诊断的Meta分析

目的 系统评价前哨淋巴结活检用于口腔鳞状细胞癌早期颈部转移诊断的临床价值.方法 检索Cochrane图书馆(cochrane library,CL)对照试验注册资料库、循证医学数据库、PubMed数据库、中国知网2001-2011年国内外关于前哨淋巴结活榆确定早期口腔鳞状细胞癌患者颈淋巴转移的文献共42篇.筛选出文献12篇,记录数据,用Meta分析的相关软件Metadisc 1.4进行统计学分析.结果 12项研究的患者共793例,最后合并的早期口腔鳞状细胞癌患者前哨淋巴结活检敏感度和特异度分别为0.86(95％可信区间:0.81 ～0.90)和0.99(95％可信区间:0.98～1.00).结论 对于早期口腔鳞状细胞癌患者前哨淋巴结活检的敏感度和特异度较高、准确率高,可以判定颈部淋巴结是否转移,以及是否需要行颈淋巴结清扫术.     

口腔鳞状细胞癌淋巴结转移相关因素的单因素分析

目的 通过分析常用的临床、病理指标与口腔鳞状细胞癌颈淋巴结转移的关系,探讨其在预测口腔鳞癌颈淋巴结转移中的价值,为临床提供预测转移的有效指标.方法 选择100例口腔鳞癌患者,记录年龄、性别、发病部位、病程、T分期、N分期等临床指标;选择肿瘤细胞浸润深度、浸润方式、病理分级、淋巴细胞浸润程度、肿瘤的粘附力、基底膜的连续性、肿瘤血管生成、肿瘤增殖等病理指标,进行统计学分析,观察这些指标与淋巴结转移的相关性.结果 单因素分析结果显示,T分期、浸润深度、平均血管密度、VEGF、PCNA和E-CD染色阳性细胞率具有统计学意义.结论 T分期、肿瘤浸润深度、E-CD、PCNA和VEGF的表达程度、肿瘤血管平均密度是与口腔鳞癌淋巴结转移相关的危险因素,可作为术前预测的指标.     

Topoisomerase expression in oral squamous cell carcinoma: relationship with cancer stem cells profiles and lymph node metastasis

J Oral Pathol Med (2012) 41 : 762–768 Background: The relationship between predictive proteins and tumors presenting cancer stem cells (CSCs) profiles in oral tumors is still poorly understood. This study aims to identify the relationship between topoisomerases I, IIα, and IIIα and putative CSCs immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. Methods: The following data were retrieved from 127 patients: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, and survival. An immunohistochemical study for topoisomerases I, IIα, and IIIα was performed in a tissue microarray containing 127 paraffin blocks of OSCCs. Results: In univariate analysis, topoisomerases expression showed significant differences according to CSCs profiles and p53 immunoexpression, but not with survival. Topoisomerases IIα and IIIα also showed significant relationship with lymph node metastasis. The multivariate test confirmed these associations. Conclusions: The results that all topoisomerases correlates with OSCC CSCs may indicate a role for topoisomerases in head and neck carcinogenesis. Notwithstanding, it is plausible that other members of topoisomerases family could represent novel therapeutical targets in oral squamous cell carcinoma.     

Gene expression profile changes correlated with lymph node metastasis in oral squamous cell carcinoma

The purpose of this research was to identify biomarkers for predicting cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). We surveyed the expressions of 1289 cancer-related genes in 41 cases of OSCC by cDNA array analysis. We extracted genes upregulated or downregulated in their expression in association with lymph node metastasis. Of 1289 cancer-related genes, we identified 39 genes differentially expressed in OSCC with or without lymph node metastasis. Expression levels of 9 genes were lower, and those of 30 genes were higher, in node-positive cases. The genes expressed at higher levels in node-positive cases included angiogenesis-related molecules, cell adhesion molecules, and proteolytic enzymes. We suggest that these characteristic genes could provide, if verifiable, useful information for predicting the risk of lymph node metastasis in OSCC.     

Ultrasonic evaluation of cervical lymph node metastasis of squamous cell carcinoma in oral cavity

Forty-four patients with oral cancer were examined by ultrasonography to detect cervical lymph nodal metastases. The lymph nodes, which were histopathologically or clinically confirmed to have cancer metastases, showed the following characteristic echogram findings: distinctive nodal boundary, posterior echo enhancement and an increased ratio of the shortest and the longest diameters of the node. It is suggested that these three peculiar ultrasonographic findings are considered to be important items for the differential diagnosis of benign nodes from the cervical metastasis of oral cancer.     

口腔癌对侧颈淋巴结转移的高危因素分析

目的：分析影响口腔癌患者发生对侧颈淋巴结转移的临床病理因素.方法：收集2010年6月～2011年6月间217例中发生对侧颈淋巴结转移的口腔癌病历资料13例,对其临床病理特点进行分析.结果：口腔癌对侧颈淋巴结转移多发于年轻患者,部位以舌、口底常见,并与临床分期、病理分级、同侧颈淋巴转移等因素密切相关,其协同作用可能加快其转移.结论：在≤45岁、肿瘤范围越过中线、侵及口底、≥T3期、低分化鳞癌、同侧颈淋巴结转移等因素中若出现两项或以上者,则有必要考虑同期行对侧颈淋巴结清扫术,以提高患者治愈率和生存率.     

前哨淋巴结活检判断口腔癌颈部淋巴结转移的系统评价

目的:系统评价前哨淋巴结活检(SLNB)预测口腔癌颈淋巴结转移的临床价值。方法:通过计算机检索CENTRAL、Medline、EMBASE、IFCC、中国生物医学文献数据库系统(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(CQVIP)、万方数据库等,收集应用前哨淋巴结活检判断口腔癌颈淋巴转移的诊断试验,应用统计软件Meta-DiSc 1.4进行数据分析。结果:纳入分析的文献9篇,前哨淋巴结活检判断口腔癌颈淋巴转移的敏感度、特异度、阳性似然比(+LR)、阴性似然比(-LR)、诊断优势比(DOR)及系统接收操作特性曲线(SROC)下面积分别为84%(95%CI 73%～92%)、100%(95%CI97%～100%)、19.16(95%CI 7.65～47.77)、0.22(95%CI 0.10～0.51)、97.72(95%CI 29.69～321.61)和0.99。结论:前哨淋巴结活检可作为临床上判断口腔癌颈淋巴结转移有效可行的方法。