DAAs治疗慢性丙型肝炎患者获得SVR后若干问题探讨

随着直接抗病毒药物(direct-acting antiviral agents,DAAs)的问世,全球范围内丙型肝炎治疗领域获得了极速发展。临床上用其治疗慢性丙型肝炎(chronic hepatitis C,CHC)有95%左右的患者获得持续病毒学应答(sustained virological response,SVR),且获得SVR后可减轻肝脏炎症,延缓肝纤维化、肝硬化进程,减少各种肝内外并发症的发生,降低肝细胞癌(hepatocellular carcinoma,HCC)发生率,但部分肝硬化患者仍会发展为HCC。所以即使获得SVR的肝硬化患者,仍需定期随访和观察。DAAs的应用让越来越多的CHC患者获得SVR,所以对获得SVR人群临床结局的探讨也越来越多。本文概述了CHC患者获得SVR后在临床不同方面的益处及存在的相关挑战。     

慢性丙型肝炎持续病毒学应答后发生肝癌患者的临床特征分析

目的研究抗HCV治疗后获得持续病毒学应答(SVR)发生肝癌(HCC)患者的临床特征。方法收集2006年至2014年郑州大学第一附属医院感染病科因慢性丙型肝炎入院抗病毒后获得SVR且未发生HCC的住院患者192例,SVR后发生HCC患者11例,分析两组患者临床特征的差异。结果 HCC组随访中位时间为17(10~39)个月,无HCC组为50(33~63)个月。HCC组初始诊断HCV感染时以及抗病毒时疾病所处的阶段为代偿期肝硬化所占比例显著高于无HCC组(54.5%比4.2%,P0.01;63.6%比16.7%,P=0.001);HCC组病毒性肝炎家族史的比例显著高于无HCC组(100%比10.4%,P0.01);HCC组SVR时白蛋白水平显著低于无HCC组[(35.0±6.0)g/L比(41.3±4.7)g/L,P=0.001];HCC组SVR时甲胎蛋白水平显著高于无HCC组[(29.8±3.2)ng/mL比(5.7±4.4)ng/mL,P0.01]。结论初始诊断HCV感染时和抗病毒时患者为代偿期肝硬化、病毒性肝炎家族史、SVR时低白蛋白水平以及SVR时较高甲胎蛋白水平可能是慢性丙肝患者SVR后HCC的危险因素。     

HCV感染者接受直接抗病毒药物治疗期间发生肝细胞癌风险

正目前慢性丙型肝炎的治疗无论在临床试验还是现实世界应用中都取得了很高的成功率。病毒学反弹仅在少数晚期肝硬化的患者中出现,与之相关的预测因素仍不明确。近来有研究发现,采用直接抗病毒药物(DAAs)治疗后获得持续病毒学应答(SVR)的HCV相关肝细胞癌(HCC)患者接受根治性治疗后意外发生"早期"HCC复发~([1-2])。而来自其他研究者的数据则显示DAAs治疗和HCC复发之间并无相关     

索非布韦联合雷迪帕韦治疗慢性丙型肝炎患者疗效研究*

目的 探讨应用索非布韦(SOF)联合雷迪帕韦(LDV)治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年8月～2020年8月我院诊治的CHC患者116例,给予SOF联合LDV治疗3个月。计算肝纤维化四指数(FIB-4),采用RT-PCR法检测HCV RNA,采用单因素和多因素Logistic回归分析影响CHC患者获得持续病毒学应答(SVR)的影响因素,应用受试者工作曲线(ROC)分析指标的预测效能。结果 在治疗结束后随访6个月,116例CHC患者血清ALT、AST和外周血PLT计数分别为(32.4±6.8)U/L、(36.5±9.2)U/L和(224.6±31.9)×10⁹/L,显著低于治疗结束时【分别为(56.6±11.7)U/L、(64.7±11.8)U/L和(262.3±41.7)×10⁹/L,P＜0.05】或治疗前【分别为(204.3±41.6)U/L、(131.2±26.5)U/L和(313.7±53.6)×10⁹/L,P＜0.05】;FIB-4和HCV RNA水平分别为(0.9±0.1)和(1.1±1.2)lgU/mL,显著低于治疗结束时【分别为(1.2±0.2)和(1.9±1.1)lgU/mL,P＜0.05】或治疗前【分别为(1.4±0.2)和(6.4±1.3)lgU/mL,P＜0.05】;本组CHC患者获得快速病毒学应答率(RVR)为75.0%,治疗结束时病毒学应答率(ETVR)为89.7%,SVR为82.0%;多因素Logistic回归分析显示,FIB-4和血清HCV RNA是影响CHC患者获得SVR的独立影响因素(P＜0.05);联合治疗前FIB-4＜1.65和血清HCV RNA载量为(6.6±0.8)lgU/mL为截断点,其预测CHC患者在治疗后获得SVR的AUC为0.875,敏感性为83.2%,特异性为90.5%。结论 SOF联合LDV治疗CHC患者可获得很好的治疗效果,FIB-4水平低和血清HCV RNA载量低的患者可能获得更好的抗病毒效果。     

丙型肝炎肝硬化直接抗病毒药物治疗的临床结局

丙型肝炎（hepatitis C，简称丙肝）抗病毒治疗已经进入直接抗病毒药物（direct antiviral agents,DAAs）时代，即使是晚期肝硬化患者经DAAs治疗也可以获得较高的持续病毒学应答（sustained virological response,SVR），但丙肝肝硬化患者经抗丙型肝炎病毒（hepatitis C virus,HCV）治疗后远期效益，如肝功能改善、失代偿肝硬化的再代偿、肝移植率、肝细胞癌（hepatocellular carcinoma,HCC）发生率等仍然值得探讨。文章对DAAs治疗丙肝肝硬化的长期随访结果进行探讨，为上述临床问题的解决提供更多依据，增强临床医生应用DAAs抗HCV治疗的信心。     

直接抗病毒药物对持续病毒学应答慢性丙型肝炎患者肝纤维化的影响

目的 评价直接抗病毒药物(DAAs)治疗对慢性丙型肝炎(CHC)患者肝纤维化状态的改善作用。方法 选取2018年1月—2021年12月期间惠州市中心人民医院首诊并接受入院规范化治疗的CHC患者104例，男性65例，女性39例，年龄(45.6±11.2)岁。CHC诊断符合要求，且获得持续病毒学应答(SVR)。比较DAAs治疗前后CHC患者各项指标变化，依据肝病状态分为慢性肝炎、代偿期肝硬化及失代偿期肝硬化，比较各CHC肝病状态治疗前后各肝纤维化指标变化值差异。Logistic二元回归分析进行单因素、多因素分析。结果 DAAs治疗前CHC患者WBC、PLT、ALT、AST及TBil分别为(5.0±1.2)×10⁹/L、(142.6±36.6)×10⁹/L、(62.0±13.7)U/L、(52.8±11.3)U/L及(21.5±5.2)μmol/L,与治疗后相比[(5.3±1.5)×10⁹/L、(171.4±41.3)×10⁹/L、(18.2±3.8)U/L、(21.6±4.1)U/L及(16.1±4.7...     

丙型肝炎基因1b型患者雷迪帕韦联合索磷布韦治疗失败后的新耐药位点NS5A-P32

正慢性丙型肝炎(CHC)是临床导致肝纤维化、肝硬化、肝癌的常见病因之一,随着直接抗病毒药物(DAAs)的出现,CHC患者的治疗出现了突破性的进展。但是随着临床上DAAs药物的广泛应用,仍有1%～15%的CHC患者治疗效果欠佳。目前研究发现HCV对药物的耐药是抗病毒治疗效果不佳的主要原因~([1])。NS5A抑制剂在CHC DAAs药物的联合治疗中发挥着重要作用,代表性药物包括达卡他韦(Daclatasvir)、雷迪帕韦     

索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化的疗效及安全性

目的观察索非布韦/达拉他韦加利巴韦林治疗丙型肝炎肝硬化患者的疗效和安全性。方法纳入2016年5月至2017年5月就诊于昆明市第三人民医院肝病科的丙型肝炎肝硬化患者129例,给予索非布韦/达拉他韦加利巴韦林抗病毒治疗12周,治疗后随访12周,观察治疗结束12周后持续性病毒学应答(SVR12)、生化学应答、肝纤维化改善和治疗期间的不良反应。结果 129例患者HCV RNA基线水平为(5.91±1.33)lgIU/mL,治疗2周时为(1.67±1.24)lgIU/mL,治疗2周75.78%患者HCV RNA达到检测下限;治疗12周时93.44%患者HCV RNA检测不到。129例患者基线的FibroScan值为(17.57±9.86);治疗12周时的FibroScan值为(8.32±1.47)kPa(与基线相比,t=15.852,P=0.000);TBil、ALT、AST基线时分别为(24.07±18.12)μmol/L、(91.42±54.56)U/L和(81.06±40.45)U/L,治疗2周时TBil、ALT、AST均显著下降(t=2.408,P=0.017;t=11.054,P=0.000;t=12.227,P=0.000),生化学应答达100%。6例未取得SVR12的患者多因素回归分析显示,复治是独立预测因子。主要不良反应为乏力和头痛,无严重不良反应发生。结论丙型肝炎肝硬化患者索非布韦/达拉他韦加利巴韦林方案可获得较高的SVR12率和生化学应答率,肝纤维化改善明显,且具有良好的安全性。     

慢性丙型肝炎患者外周血CD4~+调节性T淋巴细胞水平的变化及其与抗病毒疗效的关系

目的探讨慢性丙型肝炎(CHC)患者的外周血CD4~+调节性T淋巴细胞(Treg)的变化及其与抗病毒疗效间的关系。方法收集2013年1月-2016年1月于本院完成标准化抗病毒治疗与随访的85例CHC患者作为CHC组,选取40例同期健康志愿者为对照组。于治疗前,治疗12、48周,以及随访24周时采用流式细胞测定患者的外周血CD4~+Treg,并测定血清HCV RNA、AST、ALT水平。计量资料组间比较采用t检验。结果治疗前,CHC组的HCV RNA、AST、ALT及CD4~+Treg水平均显著高于对照组,差异有统计学意义(P值均0.001)。治疗12周时,CHC组85例患者中36例(42.35%)获得早期病毒学应答(EVR)(EVR组),另49例(57.65%)未获得EVR(no-EVR组),EVR组患者的HCV RNA和CD4~+Treg水平较治疗前均显著降低(t分别为39.241、8.763,P值均0.001),2组间HCV RNA、CD4~+Treg水平比较差异有统计学意义(t值分别为76.520、8.227,P值均0.001)。治疗48周时,CHC组85例患者中49例(57.65%)获得结束时病毒学应答(ETR)(ETR组),另36例(42.35%)未获得ETR(no-ETR组),ETR组患者治疗48周时的AST、ALT、CD4~+Treg及HCV RNA水平显著低于治疗前(t值分别为46.197、11.806、15.368、9.694,P值均0.001)和no-ETR组(t值分别为72.612、9.274、9.682、7.729,P值均0.001)。随访24周时,CHC组85例患者中39例(45.88%)获得持续病毒学应答(SVR)(SVR组),其中30例为获得EVR患者,32例为获得ETR患者,另46例(54.12%)未获得SVR(no-SVR组),SVR组治疗48周、随访24周的HCV RNA、AST、ALT及CD4~+Treg水平均显著低于no-SVR组(治疗48周:t值分别为117.564、17.113、10.564、4.452,P值均为0.001;随访24周:t值分别为11.196、20.997、13.384、7.900,P值均0.001)。结论 CHC患者存在外周血CD4~+Treg表达升高,抗病毒治疗可有效下调CD4~+Treg水平,减轻肝损伤。外周血CD4~+Treg检测可作为CHC发病及抗病毒疗效的评价指标。     

慢性HCV感染DAA应答特点和长期预后观察研究

目的 本研究旨在观察不同疾病进展阶段的HCV感染者直接抗病毒药物(direct-acting antiviral agents,DAA)治疗的应答特点和长期预后.方法 纳入2016年7月—2017年3月就诊于我中心的慢性HCV感染者127例,其中慢性丙型肝炎(chronic hepatitis C,CHC)患者85例,代偿期肝硬化(compensated-liver cirrhosis,CLC)患者32例,失代偿期肝硬化(decompensated-liver cirrhosis,DLC)患者10例.DAA治疗12或24周.比较3组患者HCV RNA转阴时间、停药后12周持续病毒学应答(sustained virologic response 12,SVR12)率以及停药后2年的转归情况.结果 所有CHC、CLC、DLC患者均完成DAA治疗.CHC、CLC和DLC患者的SVR12率分别为98.82％(84/85)、96.88％(31/32)和100％(10/10);CHC患者HCV RNA转阴时间明显早于CLC和DLC患者(P均<0.05).在2年随访期间,1例CLC患者发生病毒学复发,2例DLC患者分别出现肝功能恶化和肝细胞癌.结论 目前常用的DAA治疗方案对CHC、CLC和DLC的患者均有高效的抑制病毒复制的作用,并且SVR12率在96％～100％之间,有很高治愈率.对于肝硬化患者停药后仍须监测肝癌的发生或个别病例HCV复发等情况.     

MLN4924对索拉非尼耐药肝细胞癌细胞中neddylation修饰的抑制作用

目的 索拉非尼是美国FDA于2007年批准的治疗肝细胞癌(hepatocellular carcinoma,HCC)的一线小分子抑制剂。然而,其在HCC患者中的反应率不高。本研究旨在进一步了解索拉非尼在HCC治疗中的作用机理,为HCC靶向治疗方法的优化提供理论基础。方法 使用蛋白印迹方法检测经索拉非尼治疗前后HCC细胞中与neddylation修饰相关蛋白的表达水平。通过CCK实验检测HCC细胞的增殖速率。结果 本研究发现索拉非尼能激活neddylation修饰相关的蛋白的表达。神经前体细胞表达的发育性下调蛋白8(neuronal precursor cell-expressed developmentally down-regulated protein8,NEDD8)激活酶抑制剂MLN4924通过抑制neddylation修饰来抑制索拉非尼耐药细胞的增殖。结论 索拉非尼能引起neddylation通路的活化。泛素激活酶NAE抑制剂可以进一步抑制对索拉非尼耐药的HCC细胞的增殖。     

2011—2017年单中心儿童非病毒性肝病谱分析

目的探讨单个儿童肝病中心非病毒性肝病的疾病谱及变化趋势。方法收集2011年1月—2017年12月在我院青少年肝病诊疗中心住院诊治的0~16岁儿童非病毒性肝病患者数据,统计并分析其在同期收治的儿童肝病患者中的占比、疾病谱及病种分布。并与1983年6月—2000年12月、2001年1月—2010年12月同类病例数据作比较。结果2011年1月—2017年12月儿童非病毒性肝病患者占同期儿童肝病患者总数的23.30%(925/3967),较2001年1月—2010年12月的17.53%(703/4010)有所上升。2011年1月—2017年12月儿童非病毒性肝病疾病共72种,病例中以药物性肝损害(31.0%)最多,其次为肝豆状核变性(13.7%)和非酒精性脂肪性肝炎(11.0%);而2001年1月—2010年12月构成比前三名的疾病为肝豆状核变性(22.62%)、药物性肝损害(10.53%)和糖原累积病(9.53%)。不同年龄段居于前三位的病种分别为,1岁以下:药物性肝损害(31.3%),糖原累积病(13.4%),胆汁淤积型肝病(11.9%)。1~6岁:药物性肝损害(28.8%),肝豆状核变性(16.8%),糖原累积病(12.2%)。7~16岁:药物性肝损害(32.9%),非酒精性脂肪性肝炎(19.8%),肝豆状核变性(12.5%)。儿童非病毒性肝病重叠病毒性肝炎的发生率为11.6%(107/925),值得关注。7.8%(72/925)的儿童非病毒性肝病疑难病例通过基因检测等特殊检查得到确诊,但仍有2.9%(27/925)目前无法确诊。结论近30年来儿童非病毒性肝病占比逐渐增多,药物性肝损害和非酒精性脂肪性肝病增长迅速。质谱基因检测技术的应用进一步扩展了疾病谱。     

住院患者发生吸入性肺炎的临床特点及相关因素探讨

目的 分析探讨住院患者发生吸入性肺炎的临床特点及相关因素。方法 选择2014年1月—2018年12月于我院康复中心住院治疗的215例患者作为研究对象,收集入组患者的病历资料,分析吸入性肺炎发生的临床特点和危险因素。结果 入组215例患者中发生吸入性肺炎者45例(20.93%),45例中存在2种基础疾病者21例(46.67%)、3种者13例(28.89%)、4种者11例(24.44%);临床表现主要包括发热33例(73.33%)、有明显呛咳史25例(55.56%)、呼吸困难15例(33.33%)、意识障碍19例(42.22%)、咳嗽咳痰12例(26.67%)。Logistic回归分析显示,高龄、白蛋白水平低、合并基础疾病、咳嗽反射敏感性低、吞咽功能障碍、意识障碍、鼻饲或胃肠道营养、胃食管反流、气管插管、体位不当等均为住院患者发生吸入性肺炎的危险因素(P均<0.05)。结论 发生吸入性肺炎的住院患者以老年人群为主,且合并基础疾病多,临床症状不典型。高龄、营养状态差、生理反射障碍、意识障碍、胃食管反流、侵入性操作、体位不当等均为住院患者发生吸入性肺炎的危险因素。     

Preoperative radiation therapy for locally advanced rectal cancer: a comparison between two different time intervals to surgery

Background Although it is now considered a standard treatment to irradiate an advanced mid or low rectal tumor before surgical total mesorectal excision (TME), the optimal time interval between radiation therapy and surgery remains controversial. Materials and methods Between 1995 and 2005, patients undergoing preoperative radiation therapy and TME for locally advanced mid and low rectal tumors treated in the VU Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment in the VU Medical Center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6–8 weeks in the VU Medical Center (LI group). Preoperative tumor staging, operative data, postoperative complications, pathology results, and follow-up were compared. Results The SI group (N=57) underwent surgery after a median delay of 4 days and the LI group (N=51) after 45 days. Operative data and short-term morbidity were comparable for both groups. However, significantly higher numbers of complete remissions (12 vs 0%), tumor downstaging (55 vs 26%), and less lymph-node metastases (22 vs 44%) were found in the LI group. No significant differences were found regarding local control or long-term survival after a median follow-up of 34 months. Conclusion Several advantages, such as complete remissions and downstaging in the LI group, do not appear to have expression in a better survival or less local recurrences after a median follow-up of 34 months. Although larger (randomized) studies will be needed for definite conclusions, this may indicate that patients can be operated on within 2 weeks after radiation therapy.     

慢加急性肝衰竭诊治新思路与新方法

慢加急性肝衰竭(ACLF)在我国较为常见,其发病机制复杂、临床治疗困难、预后极差,目前已是肝病研究领域的热点问题之一。从定义、病因、预后评估及治疗方案四个方面,阐述了ACLF国内外相关研究的新进展,以期为临床诊治提供新思路与新方法,从而降低病死率,最终改善ACLF患者的临床结局。     

The relationship of histological tumor regression grade (TRG) and two different time intervals to surgery following radiation therapy for locally advanced rectal cancer

Background  The objective of this study was to assess the effect of two different time intervals between radiation therapy and surgery for rectal cancer on the histological tumor regression grade (TRG) in the resected specimen. Methods  Between 1995 and 2000, patients undergoing preoperative radiation therapy and TME for locally advanced (T3N0 and T3N1) mid and low rectal tumors treated in the VU University Medical Center or the Zaans Medical Center were entered into this study. All patients received identical radiation treatment (5 × 5 Gy) in the VU University medical center and were subsequently operated on within 2 weeks in the Zaans Medical Center (SI group) and after 6–8 weeks in the VU University Medical Center (LI group). All available histological material was reevaluated for TRG and correlated to survival. Results  Sixty-seven patients were included in the present study, 28 in the LI group and 39 in the SI group. Patient gender was comparable for both groups with 21 (75%) male patients in the LI group versus 26 (67%) male patients in the SI group (p = 0.46). A T3N0 preoperative tumor stage was found in 21 (75%) patients in the LI group and in 33 (85%) patients in the SI group (p = 0.36). All tumors were histologically proven adenocarcinoma. Patients in the SI group were significantly older (67 vs. 58 years). In the LI group, a significantly more pronounced histological tumor regression was found. A complete response (TRG1), combined with a near complete histological response (TRG 2), were present in 12 patients in the LI group and in four patients in the SI group (p = 0.002). Radicality of resection was comparable for both groups. With a follow-up of over 60 months, there were no statistically significant differences between the SI and LI groups regarding local control, overall, or disease-free survival. Conclusion  Although histological tumor regression is significantly more pronounced following a long interval between radiation therapy and surgery, in the present study, this is not reflected in a better radical resection rate, local control or better overall and disease-free survival.     

经肝动脉化疗栓塞术联合微波消融成功治疗晚期大肝癌伴肝-门静脉癌栓1例报告

随着影像学技术的不断发展,以射频消融（radiofrequency ablation,RFA）和微波消融（microwave ablation,MWA）为代表的热消融治疗,是继外科治疗后,近20年来应用最为广泛的肝癌治疗方式,不但能够完成早期肝癌的根治,还能够针对中晚期肝癌进行姑息治疗^（[1]）。相对传统的外科治疗,局部热消融具有适应证广、创伤小、可多次治疗、治疗效果好等优点,     

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38⁺⁺) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38⁺⁺ population was significantly higher (2.7±0.4%) than the LI determined by the traditional slide technique (0.6±0.1%) for 65 samples tested. Primitive plasma cells (CD38⁺⁺, CD45⁺⁺) had a higher labelling index than mature plasma cells (CD38⁺⁺, CD45⁻) (7.0±1.3% v 1.8%±0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2±2.9% v 2.2±0.7%; z =19.9, P <0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.     

Endocrine amyloid — a subject of increasing interest for the next century

Introduction.?FibroScan, a non-invasive tool for measuring liver stiffness (LS), is not specific to liver fibrosis. Other extra-hepatic conditions may modify the LS value.

Objectives.?Our aim was to examine whether amyloid deposition in the liver may modify LS.

Methods.?LS was measured prospectively in 41 patients with systemic AL amyloidosis (AL) in the French AL Reference Center, comprising: 5 patients with liver involvement (LI) and no cardiac involvement (CI), 11 with CI and no LI, 12 with both LI and CI and 13 with neither (2005 consensus criteria); 26 negative controls, 50 patients infected with Hepatitis C virus (HCV)-infected and 18 AL-free patients with right-sided heart disease (‘cardiac controls’) were also examined.

Results.?Median LS was significantly higher in patients with AL with liver involvement [27.4 (10.3–75) kPa] than in negative controls [4.8 (2.8–11.9) kPa] (p?p?=?0.001), and tended to be higher than in the ‘cardiac controls’ [11 (4.1–75) kPa] (p?=?0.08). A cut-off value of 17.3 kPa, prioritising specificity, is proposed for routine diagnosis of significant AL liver infiltration.

Conclusion.?LS?>?17.3 kPa is suggestive of AL hepatic disease in patients with non-fibrotic liver changes, and may have diagnostic value in patients with known AL.     

EGFR LI and Ki-67 LI are independent prognostic parameters influencing survivals of surgically treated squamous cell lung cancer patients

In literature there are still opinion differences concerning the prognostic significance of epidermal growth factor receptor (EGFR) expression and proliferative potential in patients with non small cell lung cancer (NSCLC). This prompted us to study those parameters. The Ki-67 labeling index (Ki-67 LI), EGFR labeling index (EGFR LI), and mitotic index (MI) were analyzed in the group of 78 consecutive, surgically treated squamous cell lung cancer (SqCLC) patients. The expression of Ki-67 and EGFR protein was visualized on formalin fixed, paraffin embedded sections using immunohistochemistry (IHC). Mitotic index was assessed on formalin fixed, paraffin embedded sections, stained with hematoxylin and eosin using morphological criteria. Mean values of Ki-67 LI and MI were higher for G2+G3 tumors than for G1 tumors. EGFR LI was higher for G1+G2 than for G3 tumors, and for pT3 than for pT1+pT2 tumors. Patients having tumors with Ki-67 < or =28% or (EGFR LI < or =13% or EGFR LI >80%) survived significantly shorter than those having tumors with Ki-67 LI >28% or 13%< EGFR LI < or =80%. In multivariate analysis, 13%> or = EGFR LI <80% and Ki-67 LI < or =28% were independent negative prognostic parameters influencing survivals of SqCLC patients.