喉癌的远处转移和相关因素分析

目的 分析与喉癌远处转移显著相关的因素。方法 回顾1990～1995年于中山大学肿瘤防治中心住院治疗的277例喉癌患者，对随访中18例出现远处转移的患者进行总结，明确喉癌远处转移的发生率、发生部位、时间以及预后情况。同时应用单因素Kaplan—Meier和多因素Cox模型分析277例喉癌远处转移的相关因素。结果 喉癌远处转移的发生率为6．5％(18／277)，肺转移占83．3％(15／18)，肝转移16．7％(3／18)，3例肺转移合并骨转移(其中椎骨1例，肋骨1例，以及多发性骨转移者1例)。2例初诊入院时即发现远处转移，其余患者从初诊入院治疗到发现远处转移的时间间隔为1～103个月，间隔中位时间为7个月。喉癌远处转移患者的3年和5年累计生存率分别为23．8％和11．9％。出现远处转移距死亡的间隔时间介于2～77个月，间隔中位时间为4．6个月。喉癌出现肝转移的预后最差，最长仅为4．6个月。对277例喉癌进行单因素Kaplan—Meier分析显示病理诊断、鳞状细胞癌病理分化程度、N分期以及临床分期是影响喉癌远处转移的显著因素。多因素Cox模型分析仅有N分期是喉癌远处转移的显著因素(Wald=7．889，P=0．005)。结论 喉癌存在一定比率的远处转移，主要发生在肺，而且预后很差。非鳞状细胞癌的其他恶性肿瘤、低分化鳞状细胞癌、颈淋巴结转移和临床晚期都可能影响喉癌的远处转移，但只有颈部N分期对喉癌远处转移具有显著的预测价值。     

尿激酶型纤溶酶原激活剂系统在喉癌中的表达及意义

目的　探讨尿激酶型纤溶酶原激活剂及其抑制剂在喉癌中的表达及与临床病理各参数及预后的关系。方法　采取免疫组化链霉卵白素生物素过氧化酶法 (labeled streptoavidin biotin peroxidase,SAB)法 ,对 10 4例喉鳞状细胞癌标本中的尿激酶型纤溶酶原激活剂 (urokinase typeplasminogenactivator,uPA)、抑制剂 (plasminogenactivatorinhibitors ,PAI)PAI 1和PAI 2表达情况进行检测。结合临床随访 ,经Kaplan Meier生存曲线、log rank检验及Cox比例风险模型分析其与临床病理参数及患者生存预后的关系。结果　uPA、PAI 1、PAI 2在喉癌组织中的表达分别为 66 3 %、70 2 %、5 0 0 %。uPA、PAI 1、PAI 2的阳性表达在颈部淋巴结转移组与非转移组中差异有显著性 ,经半定量分析P值分别为 0 0 10、0 0 2 7、0 0 3 8。单因素分析显示 :淋巴结转移及复发、肿瘤细胞分化程度、uPA和PAI 2表达是影响患者预后的因素。多因素分析提示 :淋巴结转移及复发、临床分期、uPA和PAI 2是影响患者预后的独立因素。结论　uPA在喉癌转移中起着重要的作用 ;PAI 1的作用复杂 ,可能不单纯是uPA的抑制剂 ;PAI 2可能是uPA主要抑制剂 ,由于其表达不足尚不能抑制uPA的活性     

影响喉癌手术预后的多因素分析

目的探讨影响手术治疗喉癌患者预后的相关因素。方法回顾性分析1998—2003年73例喉癌患者的临床资料,寿命表法计算生存率,用Kaplan—Meier模块进行单因素分析,Cox比例风险模型进行多因素分析。结果5年生存率54．8％。单因素分析显示临床分期、病理分型分化程度、淋巴结转移、并发症及病变部位是影响喉癌患者生存的危险因素。Cox模型显示N分期、病理分化程度、淋巴结转移和并发症是影响预后的独立危险因素。结论N分期、分化程度、淋巴结转移和并发症是影响喉癌患者生存的独立因素。     

喉癌病人外周血中期因子水平与喉癌临床特征及预后的关系

目的　研究喉癌病人外周血中期因子 (midkine,MK)水平与喉癌临床特征及预后的关系。方法　采用酶联免疫吸附测定检测喉癌病人及健康体检者 (对照组 )外周血中MK水平 ,通过SPSS软件分析MK与喉癌临床特征及预后的关系。结果　喉癌病人血清MK水平为 (40 0± 2 2 9) pg/ml,对照组为(1 1 8± 97) pg/ml,差异有统计学意义 (P <0 .0 0 1 )。以 30 0 pg/ml为分界值 ,MK阳性率随喉癌进展呈上升趋势 (P <0 .0 1 ) :I期 5 3%(1 0 / 1 9) ,Ⅱ期 6 0 %(1 8/ 30 ) ,Ⅲ期 6 2 %(2 8/ 4 5 ) ,Ⅳ期 75 %(1 5 / 2 0 )。MK水平与T分期成正相关 (P <0 .0 1 )。随访病例 5 8例 ,经Kaplan Meier生存曲线分析 ,5年生存率MK阳性者为 5 3%,阴性者为 77%,差异有统计学意义(P <0 .0 5 )。结论　高水平的MK(≥ 30 0 pg/ml)与不良预后相关。血清MK水平可以作为预测喉癌病人的生存期的一个临床指标。     

Tiam1蛋白在喉癌中的表达及其临床意义

目的检测T淋巴细胞侵袭转移诱导因子1（Tiam1）蛋白在喉癌组织中的表达,并探讨其表达水平与喉癌临床病理特征和预后之间的关系。方法采用免疫组织化学染色技术检测Tiam1蛋白在98例喉癌石蜡组织切片中的表达,并统计分析Tiam1蛋白表达水平与喉癌临床病理特征和预后之间的关系。结果Tiam1蛋白的表达与喉癌的淋巴结转移（P<0.001）、临床分期（Ⅰ期、Ⅱ期/Ⅲ期、Ⅳ期）（P=0.027）、组织病理学分级（P=0.020）及复发（P=0.003）密切相关;Kaplan Meier生存曲线分析结果显示Tiam1高表达组的5年无复发生存率（P=0.001）和5年总生存率（P<0.001）均明显低于Tiam1低表达组;而且通过Kaplan Meier生存曲线分析Tiam1蛋白表达和淋巴结转移情况与头颈鳞癌患者预后之间的关系,发现Tiam1高表达并有淋巴结转移组的5年无复发生存率和5年总生存率明显低于其它（Tiam1低表达或无淋巴结转移）组（P均<0.001）;多因素Cox比例风险回归模型进一步显示,淋巴结转移（P=0.001）及Tiam1表达水平（P=0.020）为喉癌的独立预后因素。结论Tiam1在喉癌组织中表达显著升高,且其高表达与喉癌患者的淋巴结转移、复发及预后密切相关。Tiam1可能在喉癌的发生、发展中起重要作用,其表达水平对喉癌的复发及预后具有评估价值。     

IVc期下咽癌特征分析及列线图预后模型构建

目的 探讨IVc期下咽癌患者临床特征,筛选预后影响因素,构建列线图预后模型。 方法 在监测、流行病学及预后数据库中收集IVc期下咽癌患者的临床资料,应用χ2检验分析远处转移的相关特征,单因素及多因素Cox回归分析筛选预后影响因素,并构建列线图预后模型。 结果 肺(53.7%)是最常见的转移部位。位于梨状窝的肿瘤(P=0.029)和高级别肿瘤(P=0.010)更易发生肺转移。手术、化疗、骨和肝转移是独立预后因素。基于独立预后因素的列线图预后模型C-index为0.686(95%CI 0.649-0.723)。 结论 下咽癌最易向肺转移。基于手术、化疗、有无骨转移和肝转移的列线图预后模型预测能力较好。     

174例喉癌患者手术预后及影响因素分析

目的探讨喉癌患者接受手术治疗后的生存情况及预后影响因素。方法回顾性分析2010—2014年上海长征医院耳鼻咽喉头颈外科经手术治疗的174例原发性喉癌患者的临床资料,男164例,女10例;年龄35~87岁,平均年龄(60.73 ± 9.88)岁。通过Kaplan Meier模块进行单因素分析,Cox比例风险模型行多因素分析,分析喉癌患者预后的独立影响因素。结果全组患者共174例,5年生存率64.4%;喉癌早期T1、T2期患者5年生存率达到77%。单因素分析结果显示,临床分期、病理分化程度、并发症、T分期、N分期、手术方式、颈淋巴结清扫术、肿瘤原发部位与喉癌患者术后5年生存率相关。Cox多因素分析结果显示,T分期和N分期是影响喉癌预后的独立危险因素。结论T分期、N分期是影响喉癌患者生存率的独立因素。     

乳头样和滤泡样甲状腺恶性肿瘤转移的预测因素

出现远处转移的甲状腺癌患者的预后很差，从确诊至死亡的平均时间乳头样和滤泡样甲状腺癌分别为1．9和2．2年。为探讨术后甲状腺球蛋白（Tg）血清水平和其它临床因素与肿瘤远处转移的关系，该文介绍了281例存入计算机的资料，运用Kaplan－Meier法计算实际生存率，并用Breslow和Matel－Cox法行生存率差异检验。各种重要因素的差异显著性都用Kaplan－Meier和Log－rank检验行单变量及多变量的回顾性统计学分析。结果：在对肿瘤病理类型，术后血清Tg水平、年龄、瘤体大小、手术方法、甲状腺机能等项因素的多变量分析发现，没有任何两个独立…     

头颈部鳞状细胞癌远处转移的相关因素分析

目的探讨头颈肿瘤远处转移的相关影响因素。方法对532例头颈部原发鳞状细胞癌患者的临床病理资料进行回顾性分析。选择性别、年龄、临床分期、T分级、N分级、原发癌部位、原发癌浸润深度、原发癌病理分级、有无颈淋巴结转移、颈阳性淋巴结数目、颈淋巴结转移累及区域、颈阳性淋巴结破膜情况等临床病理因素，用)(2检验和Logistic回归进行单因素和多因素分析，并用．Kaplan-Meier法对发生远隔部位转移患者进行生存分析。结果在532例头颈部原发鳞状细胞癌患者中，60例(11．3％)发生远处转移。单因素分析显示，临床分期(P=0．0126)、T分级(P=0．0082)、原发癌部位(P=0．0011)、原发癌浸润深度(P=0，0005)、有无颈淋巴结转移(P=0．0057)、颈阳性淋巴结数目(P=0．0149)、颈淋巴结转移累及区域(P=0．0034)、颈阳性淋巴结破膜情况(P=0．0118)与发生远处转移有关。多因素分析结果表明，仅原发癌部位、原发癌浸润深度与发生远处转移明显相关。用Kaplan-Meier法进行生存分析，结果显示60例发生远隔部位转移患者的1年生存率、3年生存率、5年生存率分别为51．7％、13．3％、6．5％。结论原发肿瘤部位和浸润深度是发生远处转移的共同决定性因素。而原发癌临床分期、T分级和有无颈淋巴结转移是头颈鳞癌远处转移的影响因素，但不是导致远处转移的初始和根本因素。喉癌、下咽癌以及原发癌侵犯肌肉、骨或软骨患者易发生远处转移。     

喉癌组织中微血管密度与预后的关系

目的 :探讨喉癌微血管密度与喉癌预后的关系。方法 :应用 F8相关抗体以 SABC法对 31例手术切除的喉癌微血管进行定量检测。结果 :微血管在喉癌组织学分级及分型中差异无显著性意义 (P >0 .0 5 ) ,而微血管在 2年后的淋巴结转移组 (10 .2 3± 0 .78)与无淋巴结转移组 (6 .38± 0 .33)中差异有显著性意义 (P <0 .0 5 )。结论 :喉癌间质内微血管生成与淋巴结转移和患者的预后有关。     

Risk factors for distant metastases in head and neck squamous cell carcinoma

OBJECTIVES: To evaluate the frequency of distant metastases (DM) and to determine the ability of certain clinical and pathologic factors to predict the development of distant metastases. DESIGN: Retrospective analysis. SETTING: University hospital. PATIENTS: A total of 1972 patients with oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who were treated from 1981 to 1998 and who were not diagnosed as having DM at the time of initial treatment. MAIN OUTCOME MEASURES: We evaluated the frequency of DM and the influence of different variables in their appearance. RESULTS: A total of 181 patients (9.2%) (95% confidence interval, 7.9%-10.5%) developed DM. Younger age (<45 years), hypopharyngeal localization, an advanced T stage and/or N stage tumor according to the TNM staging system, high histologic grade, and locoregional control were found to be significantly associated with the risk of DM at both univariate and multivariate analyses. CONCLUSIONS: The incidence of DM in subjects with head and neck squamous cell carcinoma is relatively low. The risk of DM is influenced by age, site of primary cancer, local and/or regional extension, grading, and achievement of locoregional control.     

Second Malignant Neoplasms in Patients Under 40 Years of Age With Laryngeal Cancer

Objectives/Hypothesis To determine the incidence of second malignant neoplasms (SMN) in patients under 40 years of age with invasive squamous cell carcinoma (SCC) of the larynx. Study Design Retrospective. Methods Using a National Cancer Institute tumor registry database encompassing 1973–1996, the incidence of SMN in patients under 40 years of age with laryngeal cancer was determined and compared with that of the registry's older, more traditional laryngeal cancer population. Median follow‐up was 136 months. Results Among the 364 patients under the age of 40 years with laryngeal cancer, 30 (8.2%) had developed a secondary malignancy to date. In comparison, 4876 (21.4%) of 22,786 patients 40 years or older with laryngeal cancer were affected by an SMN. Kaplan‐Meier analysis of the younger cohort projected 3.0%, 6.8%, and 10.7% relative risk of developing a SMN at any site over 5‐, 10‐, and 15‐year periods, respectively, after index tumor diagnosis. Similar results for the older cohort were 14.2%, 28.1%, and 39.4% at 5, 10, and 15 years, respectively. Further Kaplan‐Meier analysis demonstrated at least a fourfold increased risk for the development of secondary upper aerodigestive tract malignancies among older compared with younger patients. Conclusion Patients under 40 years of age with invasive SCC of the larynx are significantly less likely to develop a second malignancy than their older counterparts.     

喉鳞状细胞癌多原发癌81例临床报道

目的探讨喉鳞状细胞癌（简称鳞癌）多原发癌（multiple primary cancels，MPC）患者的临床特点及生存状况。方法回顾性分析1101例喉鳞癌患者中81例MPC的临床和随访资料，用Kaplan—Meier法计算生存率。结果本组喉鳞癌MPC发生率为7．4％（81／1101）。其中头颈部MPC29例（占35．8％），口腔癌和鼻咽癌最多见，有放疗史的患者较易并发头颈部MPC（X^2=5．7，P=0．017）；非头颈部MPC52例（占64．2％），以肺癌（25．9％，21／81）和食管癌（22．2％，18／81）最多见。本组消化道MPC37例（占45．7％），呼吸道MPC32例（占39．5％）。同时性MPC14例（占17．3％），中位发生时间2个月；异时性MPC67例（占82．7％），中位发生时间28个月。本组MPC病理类型以鳞癌（占66．7％）最多见，有吸烟、饮酒史的患者较易发生多原发鳞癌（P=0．007）。声门上型先证喉癌MPC中，食管癌和1：3咽癌的发生率较高（P=0．04）；声门型先证喉癌MPC中，口腔癌、鼻咽癌和肺癌的发生率较高（P=0．006）。本组总的3、5年累积生存率分别为45．2％，29．7％。其中积极治疗组（53例）5年生存率达45．5％，而因故放弃治疗患者（28例）3年生存率为0，二者比较差异有统计学意义（P=0．000）。结论喉鳞癌MPC以肺癌和食管癌最常见。有放疗史的患者较易发生头颈部MPC。有吸烟、饮酒史的患者较易发生多原发鳞癌。MPC对喉鳞癌患者预后影响较大，积极有效的治疗是提高这类患者生存率的关键。     

Screening for second primary lung cancer after treatment of laryngeal cancer

OBJECTIVES/HYPOTHESIS: As a result of smoking, patients who have received curative treatment for laryngeal cancer run a high risk of developing lung cancer. Therefore, these patients enter a screening program that aims to detect lung cancer at an asymptomatic stage. The study evaluated whether screening for lung cancer by means of regular chest x-ray examinations contributed to prolonging survival. STUDY DESIGN: A longitudinal follow-up study was performed to analyze the survival of patients who had received curative treatment for squamous cell laryngeal cancer and developed lung cancer during the follow-up period. METHODS: Patients with lung cancer were divided into two groups: 1) patients with asymptomatic screen-detected lung cancer and 2) patients with complaints indicating lung cancer, whose tumor was detected in the interval between screening examinations by chest x-ray films. RESULTS: In the complete group of patients with laryngeal cancer, no prognostic factors could be identified for developing lung cancer. There was no prolongation of survival in the screen-detected asymptomatic lung cancer patients. The median survival of both groups was 56 months (P =.57). The date of detection of the lung cancer was clearly brought forward by screening; a difference of 8 months was found between the median detection date of the two groups (P <.001). There was no difference in tumor-specific mortality between the two groups. CONCLUSION: Screening by chest x-ray examination to detect lung cancer in an asymptomatic stage after curative treatment for squamous cell laryngeal cancer does not improve survival for patients who develop lung cancer.     

Predictive value of lymph node metastases and extracapsular extension for the risk of distant metastases in laryngeal carcinoma

OBJECTIVE: The objective of this retrospective chart analysis was to determine the prognostic value of the lymph node status and extracapsular lymph node extension (ECE) of the neck for the development of distant metastases in squamous cell carcinoma of the larynx. METHODS: One hundred sixty-five patients treated for laryngeal carcinoma with a neck dissection with histologic evaluation were included. Primary study end point was distant metastasis-free survival. Univariate analysis with the Kaplan-Meier method was used to calculate distant metastasis-free survival and overall survival for the whole group and for groups according to ECE/lymph node status. Patients were classified as 1) no metastatic lymph nodes, 2) metastatic lymph nodes without ECE, or 3) metastatic lymph nodes with ECE. Univariate Cox regression was performed with outcome distant metastasis-free survival. RESULTS: The median overall survival for the whole group was 5.1 years and the 5-year survival rate was 51%. The median distant metastasis-free survival for the whole group could not be calculated and the 5-year metastasis-free survival rate was 78%. The hazard ratio was 3.4 (95% confidence interval [CI] = 1.0-12.1) for patients with positive nodes and without ECE and 10.5 (95% CI = 3.6-30.8) for the patients with metastatic nodes and with ECE compared with the patients without metastatic lymph nodes. CONCLUSION: The presence of ECE in metastatic lymph nodes augments the risk of distant metastasis by nine times in laryngeal carcinoma. Metastatic lymph nodes without ECE show a risk three times greater.     

Isolated intracranial metastasis from an early glottic cancer: how rare a presentation?

The incidence of distant metastasis with laryngeal tumors varies from 1–4% [1]. The lungs are the most frequent site, followed by bone and liver. Intracranial metastases are rarely clinically diagnosed in head neck cancer patients and if present are mainly located in the cerebrum and cerebellum. Early stage glottic squamous carcinoma with subsequent distant metastasis is rare [2]. We report a patient with T1N0 glottic tumor who underwent a curative radiotherapy and on 3 months follow up presented with isolated intracranial metastasis.     

Supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) in the management of laryngeal carcinoma: oncologic results. A 35-year experience

To evaluate the long-term oncologic results of supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) for laryngeal cancer. A 35-year retrospective study concerning 291 patients treated by supracricoid laryngectomy with CHEP for laryngeal cancer was performed. The following postoperative data were studied: recurrence rates (lymph node and laryngeal), distant metastases and second cancer. The mortality rate and overall survival were estimated by the Kaplan–Meier method. The postoperative mortality was 1.03 %. 23 patients were lost to follow-up. The 3-year survival rate was 84 % and the 5-year survival rate was 80 %. 12 patients developed distant metastasis. 31 patients developed a second cancer. The local (laryngeal) control rate was 93.94 % and the regional (cervical lymph node) control rate was 92.05 %. In multivariate analysis, the occurrence of a second non-ENT cancer and metastasis as well as margins involvement were reliable to mortality. Supracricoid laryngectomy with CHEP appears to be associated with very good long-term oncologic results and still has a place in the management of T1, T2 and selected T3 glottic cancers.     

Myc基因家族在喉癌中的异常扩增及其意义

目的探讨Ｍｙｃ基因家族在喉癌中的异常扩增及其临床意义。方法应用ＰＣＲ非变性聚丙稀酰胺凝胶电泳激光扫描技术检测了３２例喉癌组织、１２例癌旁组织和６例正常组织。结果正常组织细胞Ｍｙｃ基因无扩增，３２例喉癌中４７％（１５／３２）有Ｃｍｙｃ和Ｌｍｙｃ扩增，４１％（１３／３２）有Ｎｍｙｃ基因扩增。Ｍｙｃ基因扩增率与年龄、性别、喉癌临床分期及分化程度无关（Ｐ＞０．０５），但有淋巴结转移的患者的Ｎｍｙｃ扩增率明显高于无淋巴结转移者（Ｐ＜０．０１）。结论Ｍｙｃ基因３个成员异常扩增是喉癌发生的原因之一，Ｎｍｙｃ扩增在喉癌淋巴结转移过程中可能起正性调控作用。