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 1 990～ 1 995年于中山大学肿瘤防治中心住院治疗的 2 77例喉癌患者 ,对随访中 1 8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 2 77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 % (1 8/ 2 77) ,肺转移占83 3 % (1 5/ 1 8) ,肝转移 1 6 7% (3/ 1 8) ,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～ 1 0 3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2 3 8%和 1 1 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 2 77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 0 0 5)。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     

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。     

鼻咽癌放疗后第二原发舌癌的临床分析

目的探讨鼻咽癌放疗后第二原发舌癌的临床特点及治疗效果，探索影响其预后的因素。方法1975年1月1日-2000年12月31日在中山大学肿瘤防治中心头颈科接受首治的舌癌患者共1263例，从中筛选此前有鼻咽癌放疗史者共53例，采用Kaplan—Meier法计算累积生存率，Cox回归方法进行多因素分析。结果53例中40例患者死亡，接受治疗的51例患者总的5年和10年生存率分别为41．64％、35．69％；舌癌发生在舌尖、侧缘、舌腹和舌背分别为0例、26例（49．06％）、8例（15．09％）和19例（35．85％）；舌癌临床检查颈淋巴转移6例（11．32％）后经病理证实为3例（5．66％）；第二原发舌癌治疗后18例复发（33．96％）。单因素分析提示原发灶大小（P=0．0005）、临床TNM分期（P=0．0017）影响预后；多因素分析显示临床与病理综合分期（P=0．000）、两癌发生的时间间隔（P=0．003）是影响预后的独立因素。结论鼻咽癌放疗后第二原发舌癌发生在舌背的比例较高，其淋巴转移率较低；临床和病理综合分期以及两癌发生的时间间隔是影响预后的独立因素；对鼻咽癌放疗后第二原发舌癌进行早期诊断，行手术或包含手术的综合治疗，可能会获得更好的疗效。     

喉鳞状细胞癌组织中IL-17的表达及其临床意义

目的:检测喉鳞状细胞癌组织中IL-17的表达情况,评价IL-17的表达在喉鳞状细胞癌生物学行为和预后中的价值。方法:采用免疫组化SP法检测71例喉鳞状细胞癌及21例癌旁组织中IL-17的表达。结果:喉鳞状细胞癌组织中IL-17的表达率为54.9%(39/71),与癌旁组织(28.6%)对比差异有统计学意义(P<0.05);IL-17的表达与喉癌的分期、肿瘤分化、区域淋巴结转移、远处转移及复发有关(均P<0.05);Log-rank检验显示患者预后与肿瘤原发灶部位、原发灶分期、区域淋巴结转移、远处转移、IL-17的表达有关(P<0.05),多因素Cox回归分析发现IL-17不是影响患者预后的独立危险因素。结论:IL-17与喉鳞状细胞癌的发生、发展以及预后关系密切,是喉鳞状细胞癌患者的不良预后因素,可为喉鳞状细胞癌的抗肿瘤免疫治疗提供一定的理论依据。     

喉鳞状细胞癌组织FLIP和PTEN蛋白的表达及其临床意义

目的：研究FLIP和PTEN在喉鳞状细胞癌组织中的表达,探讨FLIP在喉鳞状细胞癌发生发展中的作用及与PTEN的关系。方法：采用免疫组织化学SP法检测45例喉癌组织以及15例癌旁组织中的FLIP和PTEN的表达。结果：FLIP在喉癌中的表达阳性率（77．8％）高于癌旁组织（33．3％）（P〈0．05）,FLIP的表达与喉鳞状细胞癌患者的临床分期及颈淋巴结转移和预后均有关。PTEN在喉癌中的表达阳性率（65．0％）高于癌旁组织（0）,（P〈0．01）,PTEN的表达与喉鳞状细胞癌的肿瘤临床分期及分化程度、颈淋巴结转移和预后有关。FLIP与PTEN在喉鳞状细胞癌中的表达呈负相关。结论：FLIP可能是喉鳞状细胞癌的一个重要的预后标记物。PTEN的表达与肿瘤临床分期、肿瘤分化和淋巴结转移有关,也可能是判断预后的一个有意义的指标。     

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。     

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。     

喉癌中血管生成素-2和基质金属蛋白酶-7的表达及临床意义

目的：研究喉癌组织中血管生成素-2（Ang-2）和基质金属蛋白酶-7（MMP-7）的表达情况及临床意义。方法：应用免疫组织化学SP法检测65例喉癌及34例癌旁喉黏膜组织中Ang-2和MMP-7的表达,分析Ang-2和MMP-7表达与喉癌浸润、转移和预后的关系。结果：喉癌组织中Ang-2和MMP-7表达的阳性率均明显高于癌旁喉黏膜组织（均P〈0．05）,且Ang-2表达与肿瘤T分期及临床分期相关（均P〈0．05）,MMP-7表达与肿瘤T分期、淋巴结转移以及临床分期相关（均P〈0．05）,而二者表达与患者年龄、病程、吸烟、饮酒、病理分化程度及临床分型无关（均P〉0．05）。喉癌组织中Ang-2和MMP-7表达存在正相关性（P〈0．05）。Kaplan—Meier生存分析显示Ang2表达与患者总生存率有密切关系（P〈0．05）,而与无瘤生存率未见明显关系（P〉0．05）;MMP-7表达与总生存率及无瘤生存率均未见明显关系（P〉0．05）。Cox回归分析显示Ang-2和MMP-7阳性表达为喉癌独立的预后因素。结论：喉癌组织中存在Ang-2和MMP-7的高表达,两者可作为临床上判断喉癌生物学行为、评估预后的客观指标。     

喉癌nm23,Cath—D和CD44表达与预后的相关因素分析

目的：探讨影响喉癌预后的相关因素。方法：采用免疫组化检测９６例喉鳞状细胞癌标本表达情况,并结合临床和病理资料分析喉癌预后因素。结果：ｎｍ２３、Ｃａｔｈ－Ｄ和ＣＤ４４的阳性表达率分别为４５．７％（４３／９４）、５２．１％（５０／９６）和４１．７％（４０／９６）。喉癌部位、大小、分化程度、Ｔ分期及ｎｍ２３表达与喉癌颈淋巴结转移有关（Ｐ〈０．０５）。结论：ｎｍ２３在喉癌中表达情况,对预测喉癌颈淋巴结转移     

喉鳞状细胞癌Cath-D和CD44的免疫组织化学检测

为研究组织蛋白酶－D（Cath－D）和CD44表达与喉癌临床、病理和预后的关系，采用免疫组织化学方法检测Cath－D和CD44在96例喉鳞状细胞癌中的表达情况。结果显示，Cath－D和CD44在喉癌中表达的阳性率分别为52．1％和41．7％；Cath－D的阳性表达与喉癌转移（包括颈淋巴结转移和远处转移）呈正相关，但单独与颈淋巴结转移无关，CD44表达与转移无关；另外，Cath－D和CD44表达与喉癌分期、细胞的病理分级、肿瘤大小和术后3年生存率均无关。提示，Cath－D在喉癌发生转移过程中可能起到一定作用。     

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.     

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。     

The impact of comorbidity on the survival of patients with laryngeal squamous cell carcinoma

Abstract Conclusions: In survival analysis, the combined Charlson comorbidity index (CCI) can be considered as a prognostic factor independent of the tumor node metastasis (TNM) classification, tumor stage, and tumor location. Severe comorbidity was the factor that had the greatest impact on prognosis in cases of initial tumor. Objective: To study the influence of comorbidity on the survival of patients undergoing surgery for larynx cancer. Methods: This was a retrospective study of the survival of 231 patients with laryngeal cancer who underwent surgery between 1995 and 2002. The CCI was used to assess comorbidity, the Kaplan-Meier method was used for survival analysis, and the Cox proportional risk regression model was used to identify independent prognostic factors. Results: The multivariate analysis of specific mortality showed that patients classified as having severe comorbidity (CCI) were more likely to die (adjusted hazard ratio (adjHR) 1.85, 95% confidence interval (CI) 1.07-3.17). This difference was more important in patients with early tumor stages than in those with advanced stages.     

梨状窝癌手术前后放疗与喉功能保全

目的探讨梨状窝鳞状细胞癌(简称梨状窝癌)手术前或手术后放疗与喉功能保全治疗的效果。方法回顾性分析1985年9月—2001年7月收治的梨状窝鳞状细胞癌134例。术前放射治疗+手术治疗(简称R+S)100例,手术+术后放疗(简称S+R)34例。随访中位时间38.1个月。结果根据KaplanMeier方法统计R+S组与S+R组3年生存率分别为54.8%、50.1%,5年生存率分别为51.1%、45.9%,差异均无统计学意义(P>0.05)。T1、T2、T3和T4期患者在R+S组与S+R组喉功能保留情况分别为4/5、3/3,66.7%(32/48)、6/6,32.4%(12/37)、0(0/16)和0(0/10)、0/9,其中T3期喉功能保留率R+S组较高,与S+R组的差异有统计学意义(P<0.05),其喉功能保留与丧失在局部复发、生存率等相关因素差异无统计学意义。R+S组和S+R组术后大体标本切缘阳性率为7.0%(7/100)和20.6%(7/34),两者差异有统计学意义(P<0.05)。Cox多因素变量分析切缘阳性、临床N分期对预后呈明显相关(P值均<0.05)。结论计划性术前放疗与术后放疗在下咽梨状窝癌的治疗上具有相同疗效。声门旁间隙受侵的T3病例选择R+S治疗可以提高喉功能的保留率,不增加预后的风险。R+S治疗方式切缘阳性率低,对喉功能的保留提供可靠客观依据。临床N分期对预后影响很大,是综合治疗的难点。     

喉癌单纯放疗失败挽救性喉切除术远期疗效及预后分析

目的 探讨喉癌单纯放疗后原发灶及颈部淋巴结残留和复发患者实施挽救性手术治疗的远期疗效及预后影响因素.方法 对72例患者进行回顾性分析,包括:放疗后原发灶及颈部复发22例,放疗后原发灶及颈部残留50例.均实施喉全切除术+经典性颈清扫术或改良性颈清扫术.应用Kaplan-Meier法计算手术后总生存率,采用Log-rank检验单因素分析临床因素对预后的影响,对影响生存率的有关因素采用Cox模型进行多因素分析.结果 实施挽救性手术的并发症发生率41 7%,其中咽瘘发生率20 8%.术后5年内肿瘤再次复发率34 7%(25/72),远处转移率22 2%(16/72),第二原发癌发生率6.9%(5/72).术后的3、5年生存率为45 8%和36 1%.复发癌N分期(rN)、肿瘤放疗失败类型、切缘情况、浸润深度、有无颈淋巴转移、淋巴结包膜侵犯和颈部非淋巴结构侵犯与患者的预后有关(P值均<0.05).多因素分析结果表明:肿瘤放疗失败类型、切缘情况、肿瘤浸润深度是影响患者预后的独立危险因素.结论 喉癌患者单纯放疗失败后应以手术挽救为主.对于术前及术中发现肿瘤侵犯肌肉及软骨的病例,特别是对根治性放疗效果不佳而肿瘤残留者,术中应充分估计肿瘤的范围,并冰冻病理检查切缘,以保证足够的安全切缘,提高挽救性手术的成功率.

Abstract：

Objective To investigate survival outcomes of salvage surgery preformed for laryngeal squamous cell carcinoma that recurred or progressed after radiotherapy alone. Methods A review of 72 patients who underwent salvage laryngectomy for laryngeal cancer failed in initial radiation therapy between 1996 and 2005 was performed. The tumor persistence occurred in 50 cases and recurrence in 22 cases. All patients received salvage total laryngectomy and radical neck dissection. Survival analysis was performed by using Kaplan-Meier method, Log-rank test and Cox proportional hazard model. Results Thirty patients developed a postoperative complication after salvage surgery. Pharyngocutaneous fistula occurred in 15 (20. 8 % ) patients. During 5 years after salvage surgery, the rates of tumor recurrence, distant metastasis and second malignancy were 34.7% , 22. 2% and 6. 9% , respectively. Kaplan-Meier analysis showed that overall 3 year and 5 year survival rates of those patients after operation were 45. 8% and 36. 1% ,respectively. Univariate analysis indicated that N restage, tumor persistence/recurrences after radiotherapy,surgical margin status, level of tumor invasion, pathologic N stage, extracapsular nodal spread and invasion of nonlymphatic structures were significantly associated with overall survival. Multivariate analysis showed the most significant prognostic factors were tumor persistence or recurrence after radiotherapy, surgical margin status and level of tumor invasion. Conclusions Surgical salvage remains the gold standard for management after failure of initial radiation therapy. The extent of tumor invasion must be assessed sufficiently before operation, and the surgical margin status must be identified in operation by using a frozen sectioning approach, especially in patients with tumor invasion to muscle/cartilage and tumor persistence after radiotherapy.     

Cancer of the nasal cavity: survival and factors influencing prognosis

OBJECTIVE: To determine overall survival and prognostic factors for cancer of the nasal cavity. DESIGN: Cross-sectional analysis of a national cancer database. METHODS: All cases of nasal cavity cancer were extracted from the Surveillance, Epidemiology and End Results database for 1988 through 1998. Cases with distant metastatic disease were excluded. Tumor histologic types, TNM staging, and pathological features were computed. Kaplan-Meier and Cox proportional hazards analyses were conducted to determine factors influencing overall survival. RESULTS: A total of 981 cases were identified, with 3.5% presenting with distant metastatic disease. After exclusion of missing variables, 783 cases were analyzed, with a mean patient age of 63.8 years. Squamous cell carcinoma was the most common tumor histologic type (49.3%), followed by esthesioneuroblastoma (13.2%). More than half of the cases presented with early (T1) primary site disease, and only 5% had positive nodal disease at presentation. Overall mean (median) survival was 76 (81) months, with an overall 5-year survival rate of 56.7%. On multivariate analysis, male sex, increasing age, T stage, N stage, and poorer tumor grade independently adversely affected survival (P<.05). Radiotherapy was administered in 50.5% of patients and also independently predicted poorer survival (P =.03). The mean (median) survival for squamous cell carcinoma was 79 (84) months; only melanoma showed a statistically significantly poorer mean survival of 40 (30) months when compared with other tumors (P<.001). CONCLUSIONS: Age, sex, and staging variables have a significant prognostic impact in nasal cavity cancer. Melanomas of the nasal cavity manifest very poor survival.     

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.     

喉癌组织中缺氧诱导因子1α和表皮生长因子受体的表达与微血管密度的关系

目的 分析喉癌组织中缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)、表皮生长因子受体(epidermal growth factor receptor,EGFR)的表达与CD105标记计数微血管密度(micro vessel density,MVD)的关系及其在评价喉癌生物学行为和预后中的价值.方法 回顾性分析1990年1月至2002年1月91例喉癌患者临床病理资料及随访结果,免疫组化法检测肿瘤组织中HIF-1α、EGFR的表达,CD105标记肿瘤组织中微血管并计数MVD.结果 HIF-1α的表达与肿瘤大小、TNM分期、T分期、淋巴转移和病理分级有关(P值均<0.05);EGFR表达与TNM分期、淋巴转移、病理分级和复发有关(P值均<0.05);MVD与喉痛部位分型、TNM分期、T分期、淋巴转移、远处转移和病理分级有关(P值均<0.05).HIF-1α、EGFR表达水平与MVD有关(F值为7.644和5.197,P值为0.001和0.025).HIF-1α与EGFR表达的相关分析差异有统计学意义(r=0.238,P=0.007).患者3年和5年生存率为56.1%和44.2%,Log-rank法单因素生存分析表明喉癌部位分型、TNM分期、HIF-1α和EGFR的表达与患者预后有关(P值均<0.05);Cox比例风险模型分析显示TNM分期和EGFR的表达为影响喉癌患者预后的独立危险因素(P值分别为0.049和0.041,RR值分别为1.300和2.417).结论 在喉癌发生和进展过程中存在HIF-1α与EGFR的异常表达,且对调节肿瘤血管生成有一定的作用,并与肿瘤的生物学行为和预后有关.