Influence of blood transfusions and preoperative anemia on long-term survival in patients operated for non-small cell lung cancer

It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis. Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy. We evaluated the influence of red blood cell (RBC) transfusions and perioperative anemia on survival in non-small cell lung carcinoma (NSCLC) patients. From 1999 through 2005, 331 consecutive patients, male/female=295/36 (mean age 64+/-9 years), who underwent radical surgery for NSCLC were prospectively enrolled in this cohort and followed up for a mean of 27.2 months. The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia. These parameters were analyzed in the whole cohort of patients and separately for stage I patients. Patients were divided according to perioperative transfusion, into Group A (transfused) and Group B (non-transfused) and according to the preoperative haemoglobin (Hb) level into Group 1(Hb<12g/dl) and Group 2(Hb> or =12g/dl), respectively. The overall transfusion rate was 25.7%. Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A (mean 33.6 months, 5-year survival 25.1%) compared to Group B (mean 48.0 months, 5-year survival 37.3%) (p=0.001). It also showed that patients with preoperative Hb level <12g/dl (Group 1), (mean of 33.0 months, 5-year survival 21.3%) had shorter survival compared to Group 2 patients (mean 49.3 months and 5-year survival 40.0%), respectively (p=0.002). Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not. In particular for stage I patients, it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis (p=0.043), while anemia was not. RBC transfusions affect adversely the survival of stage I NSCLC patients, while do not exert any effect on survival of patients with surgically resectable more advanced disease, where preoperative anemia is an independent negative prognostic factor. These findings indicate that RBC transfusion might exert an immunomodulatory effect on patients with early disease while in more advanced stages this effect is not apparent.     

246例非小细胞肺癌的预后影响因素分析

目的:分析246例非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的预后影响因素.方法:回顾性分析2010年1月至2014年12月246例非小细胞肺癌患者临床资料,采用Kaplan-Meier法进行生存分析,Log-rank检验和Cox模型预后影响因素行单因素和多因素分析.结果:全组患者中位生存时间为37.44个月.1年、3年、5年总生存率分别为72％、46％、26％.单因素分析显示,男性、年龄＞75岁、晚期、有吸烟史、有肝转移、无手术史非小细胞肺癌患者的中位生存期明显缩短(P＜0.05或P＜0.01).多因素分析显示,性别、疾病分期、是否吸烟和是否手术是影响非小细胞肺癌预后的独立因素(P ＜0.05或P＜0.01).结论:性别、疾病分期、是否吸烟和是否手术是非小细胞肺癌的独立预后因素.     

Maximum SUV on positron emission tomography and serum CEA level as prognostic factors after curative resection for non-small cell lung cancer

Aims: The relationship between the maximum standardized uptake values (SUVmax) on positron emission tomography (PET) and serum carcinoembryonic antigen (CEA) level in non‐small cell lung cancer (NSCLC) patients was investigated. Methods: Consecutively, 197 surgically resected NSCLC patients with preoperative staging including serum CEA and PET were reviewed retrospectively. Results: When patients were subdivided into two groups based on the median value of the SUVmax (6.6), the 5‐year survival of patients with a high SUVmax was 63.20%, which was significantly worse than patients with a low SUVmax (87.29%, P = 0.0004). The 5‐year survival of patients with normal and high serum CEA level was 82.70 and 51.08%, respectively (P < 0.0001). Univariate and multivariate analyses indicated the independent prognostic impact of the SUVmax and serum CEA level. Patients with both low SUVmax and normal serum CEA level had favorable prognosis, whereas those with both high SUVmax and high serum CEA level had poor prognosis. Conclusion: Preoperative SUVmax and serum CEA level are independent prognostic factors for survival in NSCLC. The combined use of preoperative SUVmax and serum CEA level might be a better prognostic indicator.     

280例非小细胞肺癌患者围手术期输血与否的预后关系

目的:研究非小细胞肺癌术后的预后因素及围手术期输血对术后无病生存的影响。方法:回顾性调查了280例手术切除的非小细胞肺癌患者,其中145例(51.8%)患者围手术期接受了输血治疗,采用单因素对数秩检验(log-rank test)和多因素Cox比例风险回归模型进行分析。结果:多因素分析表明,影响预后的主要因素有分化程度、术后分期、围手术期输血。围手术期输血是无病生存的独立预后因素。结论:围手术期输血是非小细胞肺癌独立的不利预后因素,应当尽量避免围手术期输血。     

CD133 expression: a potential prognostic marker for non-small cell lung cancers

Background

CD133 is a membrane glycoprotein containing five transmembrane loops. Previous reports suggest that a CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal characteristics has biological features of a cancer stem cell. In addition, the presence of CD133-positive cells was associated with a significantly poorer prognosis for some solid tumors, compared to those with CD133-negative cells. However, the clinicopathological significance of CD133 in non-small cell lung cancer (NSCLC) remains controversial.

Methods

We conducted immunohistochemical assessment of 161 NSCLCs surgically resected at Hokkaido University Hospital between 1982 and 1994 to evaluate correlations between CD133 expression and various clinicopathological features.

Results

CD133 expression was significantly correlated with pathological stages (pStages) II, III, and IV for the various NSCLC types analyzed and was an independent factor for unfavorable prognosis in this population (hazard ratio = 3.157, P = 0.015).

Conclusion

CD133 expression was correlated with pStage and was predictive of unfavorable prognosis in patients with pStages II, III, and IV NSCLC. These results suggest the possibility of using CD133 as a novel prognostic marker in these patients.     

Ⅰ期非小细胞肺癌预后因素的研究

目的 探讨Ⅰ期非小细胞肺癌(NSCLC)的联合预后因素。方法 回顾性分析58例Ⅰ期NSCLC患者的临床资料、术后病理结果和免疫组化技术检测的9项基因表达指标(c-myc、MDM2、c-erbB-2、EGFR、p53、p14^ARF、p16^INK4、p21^WAF1、nm23)。观察患者的总生存率、局部区域性复发率和远处转移率。结果 全组5年生存率、局部区域性复发率和远处转移率分别为71．1％,11．1％和33．5％。单因素分析结果表明,肿瘤细胞的低分化是影响总生存率的不良预后因素(P=0.028);c—myc与c-erbB-2的高表达均为影响总生存率和远处转移率的不良预后因素;促进肿瘤增殖基因总分组的高分值(P=0．041)与综合肿瘤基因组的高分值(P=0．006),是总生存率的不良预后因素。多因素分析结果表明,肿瘤细胞的分化程度与综合肿瘤基因的联合表达,是影响总生存率的独立预后因素。本组结果还显示,已行化疗的高危组患者,其总生存率与无远处转移率均优于未行化疗者,但差异尚未见有显著性。结论 肿瘤细胞的分化程度与综合肿瘤基因的表达,可能是Ⅰ期NSCLC的预后因素。高危组患者进行术后化疗似有提高疗效的趋势。     

非小细胞肺癌免疫治疗疗效预测的研究进展

近年来,免疫检查点抑制剂(immune checkpoint inhibitors,ICI)治疗晚期非小细胞肺癌进入了一个新纪元,但不同于靶向治疗,免疫治疗没有明确的疗效预测因子以指导临床。目前应用较多的是程序性死亡受体配体(programmed cell death ligand 1,PD-L1)表达的检测,然而多项临床试验结果提示只有约20%的NSCLC患者能从中获益。而肿瘤突变负荷(tumor mutation burden,TMB)也逐渐兴起,还有许多检测因子尚在发现中。本综述旨在探讨非小细胞肺癌中免疫治疗的疗效预测因子以更好地指导临床。     

非小细胞肺癌疗效预测因子基因多态性的研究

     切除交错互补修复基因、核糖核苷酸还原酶M1亚单位、P53、表皮生长因子受体、血管表皮生长因子与非小细胞肺癌（NSCLC）的疗效及预后密切相关。近年来,许多研究对上述因子的多态性与NSCLC疗效及预后进行相关探讨,其基因多态性有望成为NSCLC患者的预后预测标志。     

可手术非小细胞肺癌的预后因素分析

目的:探讨术前、术后辅助化疗的Ⅱ、Ⅲ期非小细胞肺癌手术患者的多种预后因素。方法:对1995年1月～2002年9月65例围手术期化疗非小细胞肺癌患者的临床、病理资料进行回顾性研究,用Kaplan-Meier曲线、生命表法及Log-Rank法检验生存率差异,用Cox单、多因素分析评价各因素对预后的影响。结果:65例非小细胞肺癌的1、3、5年生存率分别为84.13%、37.88%和10.18%。单因素分析显示综合分期、手术根治情况、术后化疗周期数、肿瘤侵犯情况、胸内淋巴结、肿瘤单径大小、肺门情况、出血量、术后首次化疗距手术时间明显影响生存;Cox多因素分析中,肿瘤单径大小及术后化疗周期数为影响预后的独立因素。结论:肿瘤单径大小及术后化疗周期数是影响Ⅱ、Ⅲ期非小细胞肺癌预后的重要因素。     

1826例非小细胞肺癌的预后因素分析

目的 探讨影响非小细胞肺癌(NSCLC)预后的相关因素,分析分期和脉管瘤栓对非小细胞肺癌预后的影响.方法 回顾1826例NSCLC患者的临床资料,将可能影响NSCLC预后的风险因子进行单因素和多因素分析,确定NSCLC预后的影响因素.应用Kaplan-Meier法分析分期和脉管瘤栓对患者生存率的影响.结果 单因素分析显示,影响NSCLC预后的因素为肿瘤家族史(P=0.02)、组织学类型(P=0.005)、分期(P=0.002)和脉管瘤栓(P=0.002).经Cox回归分析,分期为Ⅲ期和有脉管瘤栓是影响NSCLC预后的独立危险因素.Ⅰ、Ⅱ、Ⅲ期患者的5年生存率分别为57.4%、34.2%和18.7%(P=0.001),同一分期中,有无脉管瘤栓患者的生存率差异有统计学意义(P＜0.05),有脉管瘤栓或无脉管瘤栓者在各分期之间的生存率差异亦有统计学意义(P＜0.05),有脉管瘤栓患者复发或转移的发生率(69.9%)显著高于无脉管瘤栓者(36.7%,P＜0.001).结论 分期和脉管瘤栓是影响NSCLC预后的重要因素,并且脉管瘤栓还可作为判断NSCLC侵袭和转移的重要因子.     

Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers

BACKGROUND: Apoptosis related proteins in early staged NSCLC seem to have prognostic value. We studied the value of a combination of eight of those proteins in advanced NSCLC. PATIENTS AND METHODS: Bronchoscopically procured tumor biopsies of NSCLC patients were stained immunohistochemically and rated for expression of eight different cellular proteins. Patients were treated with 60 Gy radiotherapy with or without carboplatin as radiosensitizer. RESULTS: Apoptotic proteins in tumors that showed positive staining were the highest for Bax (99%), Fas (92%), FasL (87%), Rb (87%), p21(WAF1) (73%), and p53 (70%), and the lowest for c-myc (58%) and Bcl-2 (58%). In the Cox regression analysis Bcl-2 positivity (RR = 0.61, 95% CI, 0.37-0.98, p = 0.04) was predictive for overall survival. Only Bcl-2 staining percentage (RR(10) (RR associated with an increase in stained cells of 10%) = 0.93, 95% CI, 0.89-0.99), p53 (RR(10) = 0.94, 95% CI, 0.89-0.99) and FasL (RR(10) = 0.92, 95% CI, 0.86-0.99) were predictive for a longer progression-free survival. No specific constellation of apoptotic proteins was associated with tumor response. CONCLUSION: Bcl-2 expression in tumor tissue of patients with unresectable NSCLC predicts a better overall survival, while Bcl-2, p53, and FasL expressions predict for a longer progression-free survival.     

Cyclin E expression, a potential prognostic marker for non-small cell lung cancers.

Cyclin E is a G1 cyclin that has been shown to be one of the key regulators of the G1-S transition and could consequently be a deregulated molecule in tumors. In the present study, we have characterized cyclin E expression by immunohistochemistry in 217 resected non-small cell lung cancers (NSCLCs) and found large variations in cyclin E expression among tumors. High-level cyclin E expression (a cyclin E-labeling index > or =30%), observed in 115 (53%) of 217 NSCLCs, was more frequently found in tumors from smokers than from nonsmokers (P = 0.001), in squamous cell carcinomas than in nonsquamous cell carcinomas (P = 0.0002), and in pT2-4 tumors than in pT1 tumors (P = 0.04) by the chi2 test. Multivariate logistic regression analysis for the correlation between cyclin E expression and various characteristics showed a significant association of high-level cyclin E expression with squamous cell carcinomas (P = 0.005). Patients with tumors having high-level cyclin E expression survived a significantly shorter time than patients with tumors having low-level expression, both among the 151 patients with potentially curatively resected NSCLCs (5-year survival rates, 48 and 63%, respectively; P = 0.03) and the 103 patients with p stage I NSCLCs (5-year survival rates, 57 and 81%, respectively; P = 0.007). High-level cyclin E expression was also a significant and independent unfavorable prognostic factor in both patients with potentially curatively resected NSCLCs (P = 0.01) and in those with p stage I NSCLCs (P = 0.03) by Cox's proportional hazards model analysis. These findings indicate that cyclin E may play a pivotal role for the biological behavior of NSCLCs, and that a high level of cyclin E expression may be a new prognostic marker for NSCLCs.     

207例淋巴结阴性的早期非小细胞肺癌的临床病理特征及预后分析

目的:对行手术切除的淋巴结阴性的早期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的临床病理特征及影响术后生存预后因素进行分析.方法:纳入2008年1月至2013年12月于四川大学华西医院诊治,行手术切除且经病理确诊为非小细胞肺癌,肿瘤直径≤7cm,且无淋巴结及远处转移的患者,回顾性分析其一般临床特征以及术后生存预后的影响因素.结果:共纳入207例非小细胞肺癌患者,其中男性137例(66.2％),女性70例(33.8％);平均年龄60.1岁(38 ～ 80岁);有吸烟史患者113例(54.6％);病理类型以腺癌121例(58.5％)为主;病变部位主要位于肺上叶(右肺上叶65例,左肺上叶39例);有脏层胸膜浸润的肺癌患者101例(48.8％).肿瘤直径≤3cm、＞3～5cm和＞5～ 7cm的患者五年生存率分别为80.0％、63.6％、41.5％.多因素分析提示年龄＞65岁(HR:1.071,95％ CI:1.026 ～1.118,P=0.001)、肿瘤直径≤3cm(HR:0.767,95％ CI:0.630 ～ 0.930,P=0.007)及有脏层胸膜浸润(HR:2.058,95％CI:1.134～3.735,P=0.018)是影响淋巴结阴性的早期非小细胞肺癌患者生存预后的独立危险因素.结论:淋巴结阴性的早期非小细胞肺癌患者以男性居多,腺癌为主;肿瘤直径、患者年龄和脏层胸膜浸润是影响早期无淋巴结转移的肺癌患者的独立危险因素.     

110例局部非小细胞肺癌手术治疗的预后分析

目的:探讨手术治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）患者的临床病理特征与预后的关系。方法:回顾分析110例NSCLC患者的临床资料,临床病理特征和治疗情况,并用Kaplan-Meier法进行预后分析。结果:110例NSCLC患者,男女比例为2.79∶1;年龄31~84岁,中位年龄63岁,＜65岁的61例,≥65岁的49例。中位生存时间为67个月。单因素分析结果显示,老年（P=0.026）、淋巴结转移阳性（P=0.049）及Ⅲ期患者（P=0.000）预后差。多因素分析结果显示年龄（P=0.014）及临床分期（P=0.001）是影响NSCLC患者生存的独立预后因素。亚组分析结果显示淋巴结转移阳性的NSCLC患者中,肿瘤位于右肺（P=0.005）及肿瘤最大径＞5 cm组（P=0.014）预后较差。结论:老年、临床分期为Ⅲ期、有淋巴结转移且肿瘤位于右肺及直径大于5 cm的患者预后差。     

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer

Purpose

This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer.

Subjects

This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008.

Results

The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19–88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p < 0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213–5.442, p = 0.014).

Conclusion

A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion.     

Preoperative evaluation and risk factors in patients undergoing lung resection for cancer

Surgical resection remains the mainstay of treatment in lung cancer patients. Stratification of preoperative risk should be based on the functional status of pulmonary and cardiac systems usually damaged by cigarette smoking. Preoperative pulmonary evaluation should be performed taking into consideration the specific characteristics of the single patient and the type of surgery planned. Spirometry only may be required or oxygen consumption determination is necessary. Cardiac assessment should be based on clinical and instrumental examinations while invasive tests should be limited to high-risk patients. The potential difficulties in endotracheal intubation and lung isolation, the risk for desaturation during one-lung ventilation, and postoperative pain control should be analyzed.     

Biological prognostic factors for early stage completely resected non-small cell lung cancer

BACKGROUND AND OBJECTIVES: The different and unpredictable outcomes in early-stage non-small cell lung cancer patients requires urgent research concerning the biological pathway of this neoplasm. Our study investigated the frequency of expression and the clinicopathologic and prognostic significance of a series of biological markers in stage I and II resected non-small cell lung cancer. METHODS: A total of 99 cases of pathologic stage I and II were analyzed. The mean follow-up of surviving patients was 41 months. The expressions of the following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biological markers using Cox's model for multivariate analysis. RESULTS: Tumoral vessel invasion was present in 22 (22%) pathologic samples, the angiogenesis mean value was 37 +/- 13, and median was 35; 13 (13%) patients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotein expression was present in 48 patients (48.5%). All samples presented Ki-67 expression (mean value = 25.3 +/- 19.3, median = 20). The pathologic staging of the tumor was the most important independent prognostic factor for survival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vessel invasion was the only marker with an independent predictive factor for survival and recurrence of disease in the group of patients without lymph node involvement (P = 0.02). CONCLUSION: Our data do not support a relevant prognostic role for p53, bcl-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor vessel invasion was an independent predictive factor of poor outcome in the group of patients without lymph node involvement. Pathological stage was confirmed as the most important independent prognostic factor.