A clinicopathological study of early gastric cancers with a diameter larger than five centimeters

Out of a total of 1,112 resected early gastric carcinomas, 181 that were larger than 5 cm in diameter have been pathologically investigated. Of these, intramucosal and submucosal carcinomas amounted to 68 (37.6%) and 113 (64.4%), respectively. The incidence of their location, shown as a percentage, was 37.8% in the antrum, 57.4% in the corpus, and 4.8% in the fundus (11% in the anterior wall, 13.2% in the posterior wall, 68.1% in the lesser curvature, and 7.7% in the greater curvature). Grossly, the incidence of a type IIc carcinoma was 46.5% and that of a IIc + III type was 20.5%, respectively. Microscopically, in the intramucosal cases, signet ring cell carcinomas were the most frequent histological type, whereas in the invasive submucosal cases, the carcinomas were the intestinal metaplastic type. Lymphatic invasions, venous invasions, and lymph nodal metastases amounted to 32.6%, 6.1%, and 11.6%, respectively. In the early gastric carcinomas, the larger the tumor size, the more likelihood of a signet ring cell carcinoma than a intestinal metaplastic type, and it appeared that a signet ring cell carcinoma had infiltrated the propria mucosae for a longer time when compared to either an intestinal metaplastic type carcinoma or a poorly differentiated tubular adenocarcinoma.     

Prognostic value of smoking status in operated non-small cell lung cancer

Despite the indisputable link between smoking and the increased risk for lung cancer, the inclusion of this factor in prognostic survival analysis has been scarce. Important clinical questions regarding the smoking status are the basis of this study and are as follow: what is the prognostic benefit of having been a non-smoker or having stopped smoking prior to developing lung cancer and what is the prognostic benefit of smoking cessation at the time of diagnosis of lung cancer? Cigarette smoking status of 311 patients operated for non-small cell lung cancer (NSCLC) by a single surgeon was determined based on two independent questionnaires taken prospectively prior to lung operation. Of all patients analysed, 169 (54.3%) were current smokers, 25 (8.0%) were non-smokers, 82 (26.4%) were former smokers and 35 (11.3%) were recent quitters. A Cox multiple regression model was used to test the prognostic value of smoking status on survival together with other relevant clinicopathological factors. For overall survival, older age (P = 0.011), presence of lymph node metastases (P < 0.001) and current smoking (P = 0.001) were independent predictors of poor prognosis, while non-smokers (relative risk = 0.447, 95% confidence interval = 0.206-0.970, P = 0.042), former smokers (relative risk = 0.543, 95% confidence interval = 0.350-0.843, P = 0.006) and recent quitters (relative risk = 0.340, 95% confidence interval = 0.164-0.705, P = 0.004) had a significant better prognosis compared to current smokers (referent group). Similar results were obtained for disease-free survival. These results indicate that smoking cessation is beneficial for lung cancer patients at any time point prior to lung operation and current smoking at the time of operation is associated with poor prognosis.     

Prognosis for resected lung cancer patients with tumors greater than ten centimeters in diameter

During the period 1962-1986, 43 lung cancer patients, 2.3% of the 1,832 patients who underwent pulmonary resections at the National Cancer Center Hospital, Tokyo, had tumors greater than 10 cm in diameter. These 43 cancers were classified postsurgically according to the 1987 guidelines for TNM classification of malignant tumors established by Union Internationale Contre le Cancer (UICC), and included 35 cases (81.0%) in stages IIIA, IIIB and IV. The histological tumor types were adenocarcinoma in 18 cases (41.9%), squamous cell carcinoma in 13 (30.2%), large cell carcinoma in 11 (25.6%) and adenosquamous cell carcinoma in one (2.3%). Twenty-two patients underwent pneumonectomy and 21, lobectomy. In terms of the radical extent of surgery, 16 patients underwent a curative operation (37.2%) and 27 received non-curative surgery (62.8%). Excluding one patient who died of an unknown postoperative cause, the overall cumulative five-year survival rate was 19.7%. There was, however, no significant difference in five-year survival rates between the patients who underwent a curative operation (21.5%) and those who received non-curative surgery (18.8%). There was no significant difference in five-year survival rates between patients with adenocarcinoma (21.2%), those with squamous cell carcinoma (15.4%) and those with large cell carcinoma (27.3%). There was little difference in five-year survival rates between patients with postoperative stage I or stage II tumors (25.0%), patients with stage IIIA tumors (9.5%), patients with stage IIIB tumors (30.0%) and patients with stage IV tumors (20.0%), while the five-year survival rates for patients with postoperative N0 disease were 33.3%, N1 disease 28.9% and N2 disease 0%. Among the 42 patients the survival study, there were eight long-term survivors (greater than 5 yr), all of whom had been in N0 or N1 stage and four of whom had undergone curative surgery. Two were classified as being in stage T4 with malignant pleural effusions, and the other two as being in stage M1 with intrapulmonary metastasis. Patients with N2 disease have an unfavorable prognosis and may be considered suitable for studies on adjuvant therapy, although the relative influence of other prognostic factors must be considered. Classifying the tumors according to whether or not they had reached 10 cm in diameter was of no importance.     

炎性复合指标与非小细胞肺癌预后关系的研究进展

肺癌是一种炎症相关性疾病,长期慢性肺部炎症可增加肺癌罹患风险。非小细胞肺癌（non-small cell lung cancer,NSCLC）为肺癌最常见类型,具有发病率高,早期确诊率低,预后差的特点。研究表明,肿瘤相关性炎症反应广泛参与肿瘤起始、增殖、侵袭及转移各阶段,与疾病预后密切相关。基于炎症标志物建立的炎性复合指标有望成为非小细胞肺癌预后评估的有效指标,对准确评估病情、识别生存风险、改善远期预后具有现实意义。     

Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer

Tumor Biology - The serum tumor markers CYFRA 21–1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung...     

Prognostic factors in non-small cell lung cancer

Identification of prognostic factors is critical in optimizing treatment for patients with cancer. The purpose of this work is to review the modern literature with regard to prognostic factors for patients with non-small-cell lung cancer (NSCLC) taking into account ongoing advances in clinical evaluation, staging, surgery, radiation therapy, chemotherapy, and molecular biology in this widely heterogeneous patient population.     

Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer

Background

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).

Methods

Immunohistochemical staining was performed on deparaffinized specimens from 82 patients with stage I-IV NSCLC using a polyclonal anti-XOR rabbit antibody. Cytoplasmic XOR staining was scored on frequency and intensity scales from 0 to 4 with low expression defined as 0-1 and high expression defined as ≥2-4. XOR immunostaining was correlated with clinical characteristics and outcomes and analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results

Positive XOR expression was observed in 53/82 cases (65%). Patients with high XOR frequency had a longer median survival of 3053 days (95% CI: 2190-3916) vs. 592 days (95% CI: 492-692 days) for patients with low XOR frequency, p = 0.0089, HR 0.47. Neither XOR intensity nor the overall score of XOR frequency multiplied by XOR intensity demonstrated any significant association with survival. Surgical resection was performed on 61 patients of which 34 (56%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy with low XOR expression, 15/34 (44%) had a shortened median survival compared with patients who received adjuvant chemotherapy with high XOR expression (543 days vs. 2023 days, respectively, p = 0.007 and HR = 0.33).

Conclusion

Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with NSCLC who received adjuvant chemotherapy. Further studies of the XOR pathway are warranted to validate and mechanistically explain these outcomes.     

Relationship between tumor size and disease stage in non-small cell lung cancer

Background  

Whether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC).     

血清肿瘤标志联合检测对非小细胞肺癌诊断价值的探讨

目的:探讨血清肿瘤标志细胞角蛋白19片段抗原(CYFRA21-1)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、糖链抗原125(CA125)、胃泌素释放肽前体(ProGRP)的水平在非小细胞肺癌(NSCLC)诊断中的应用价值.方法:采用酶联免疫法(ELISA)测定120例NSCLC患者和120例肺良性病变患者的血清肿瘤标志CYFRA21-1、CEA、NSE、CA125和ProGRP的水平.结果:NSCLC组5种血清肿瘤标志的水平和阳性检测率均显著高于良性病变组,P<0.05.5种血清肿瘤标志在NSCLC诊断中的特异性较高,CYFRA21-1、CEA、NSE的敏感性较高,而CA125和ProGRP敏感性较低.5种血清肿瘤标志联合检测在NSCLC诊断中的敏感性和特异性分别为92.5%和84.2%.结论:多种肿瘤标志联合检测可以提高NSCLC诊断的敏感性,对NSCLC的早期诊断和鉴别具有重要的临床价值.     

术前红细胞分布宽度对非小细胞肺癌患者预后的评估价值

  目的  分析术前红细胞分布宽度（red cell distribution width,RDW）对非小细胞肺癌（non-small cell lung cancer,NSCLC）患者预后的评估价值。  方法  回顾性分析2008年3月至2012年12月天津医科大学肿瘤医院行根治性手术的513例NSCLC患者的临床病理资料。根据受试者工作特征ROC曲线分析确定RDW的截断值。分别通过χ2、t或秩和检验分析RDW与临床病理特征和实验室变量之间的关系,采用Kaplan-Meier法进行生存分析,Log-rank检验组间生存差异。采用Cox比例风险回归模型进行多因素分析。  结果  根据ROC曲线,术前RDW最佳截断值为12.95%。其中RDW≤12.95%为250例,RDW>12.95%为263例。术前RDW与年龄、血红蛋白、白蛋白、纤维蛋白原和D-二聚体水平显著相关（均P < 0.05）。单因素分析显示肿瘤位置、病理分期、血小板数目、白蛋白、血红蛋白、纤维蛋白原和术前RDW是影响NSCLC患者预后的因素（均P < 0.05）;多因素分析显示术前RDW和病理分期是影响NSCLC患者预后的独立危险因素（均P < 0.05）。  结论  术前RDW水平可作为预测行根治性手术的NSCLC患者预后的指标。      

A survival analysis using physique-adjusted tumor size of non-small cell lung cancer

Background

Differences in individual body sizes have not been well considered when analyzing the survival of patients with non-small cell lung cancer (NSCLC). We hypothesized that physique-adjusted tumor size is superior to actual tumor size in predicting the prognosis.

Methods

Eight hundred and forty-two patients who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor size was defined as: x-adjusted tumor size = tumor size × mean value of x/individual value of x [x = height, weight, body surface area (BSA), or body mass index (BMI)]. Tumor size category was defined as ≤2, 2–3, 3–5, 5–7, and >7 cm. The separation index (SEP), which is the weighted mean of the absolute value of estimated regression coefficients over the subgroups with respect to a reference group, was used to measure the separation of subgroups.

Results

The mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m², and 22.2 kg/m², respectively. The 5-year survival rates ranged from 88?59% in the non-adjusted tumor size model (SEP 1.937), from 90?57% in the height-adjusted model (SEP 2.236), from 91?52% in the weight-adjusted model (SEP 2.146), from 90?56% in the BSA-adjusted model (SEP 2.077), and from 91?51% in the BMI-adjusted model (SEP 2.169).

Conclusions

The physique-adjusted tumor size can separate the survival better than the actual tumor size.

     

18F-FDG PET对非小细胞肺癌预后预测价值的研究进展

目的:探讨18F-FDG PET对非小细胞肺癌预后的研究进展,指导临床中PET的应用.方法:应用计算机在PUBMED数据库检索2002～2007年有关18F-FDG PET对非小细胞肺癌预后的文章,并限定文献语种为英文,检索词fluorodeoxyglucose (FDG)、positron emmition tomography (PET)和non-small cell lung cancer和prognosis.同时,计算机检索中国期刊全文数据库2002～2007年的相关文章,检索词为PET和肺肿瘤,限定文章语言种类为中文.对选择的资料进行初审,选取和PDGPET以及与其非小细胞肺癌预后相关的文献,然后查找全文.排除标准:1)重复研究;2)个案报道.共收集到相关文献59篇,排除重复或类似的同一研究,最终纳入30篇符合标准的文献.结果:大部分研究证明,肺癌原发灶的18F-氟脱氧葡萄糖(18F-FDG)标准摄取值(standardized uptake value, SUV)与患者的预后相关,治疗前后SUV值高的患者预后相对SUV值低的患者对放化疗敏感性差;进一步的研究显示,其复发的概率相对高,预后较差.但是放疗前后SUV变化能否作为独立的预后因素尚存在争议.结论:PET在非小细胞肺癌的预后判断方面有重要意义.不仅可以广泛用于放化疗疗效评价,也可用于预测肺癌治疗后复发以及对患者生存期的预测.     

Prognostic value of matrix metalloproteinase-7 expression in patients with non-small cell lung cancer

The prognostic value of matrix metalloproteinase-7 (MMP-7) for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. We performed a meta-analysis of the literatures to clarify its impact. Trials were selected for meta-analysis if they provided an independent assessment of MMP-7 in NSCLC and reported the analysis of survival data based on MMP-7 status. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to evaluate the associations between MMP-7 expression and survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Seven studies involving 1,446 patients were identified. The combined HR for all studies was 1.28 (95 % CI 0.86–1.91; P?=?0.22). Subgroup analysis revealed that MMP-7 overexpression had a favorable impact on survival in Caucasians (HR?=?0.74; 95 % CI 0.55–0.99; P?=?0.043) but showed a poor survival prognosis in Asians (HR?=?1.74; 95 % CI 1.05–2.88, P?=?0.031). Its effect also appeared significant when the analysis was restricted to Asian patients with squamous cell cancer (HR?=?3.42; 95 % CI 1.92–6.11, P?=?0.000) and adenocarcinoma (HR?=?2.1; 95 % CI 1.34–3.29, P?=?0.001). Our meta-analysis suggests that there are ethnic differences in the clinical significance of MMP-7 expression for patients with NSCLC.     

胸部CT特征对克唑替尼治疗晚期非小细胞肺癌疗效及预后的预测价值

  目的  探究治疗前胸部CT特征对克唑替尼（crizotinib）治疗晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）患者疗效及预后的预测价值。  方法  分析2014年1月至2017年3月经克唑替尼治疗的晚期NSCLC患者47例的临床资料。对其临床资料及治疗前胸部CT图像进行分析，根据实体瘤疗效评价标准（RECIST）1.1对治疗效果进行随访评价，并记录无进展生存期（progression-free survival，PFS）。  结果  所有患者的中位PFS为10个月。胸部CT特征与克唑替尼疗效无相关性（P>0.05）。单因素生存分析显示，肿瘤较大（P=0.009）、中央型（P=0.002）、存在实变（P=0.002）、存在胸腔积液（P=0.001）或存在癌性淋巴管炎（P=0.019）提示患者PFS较短。Cox多因素回归分析显示，病变位置（HR=3.219，95%CI:1.517~6.833；P=0.002）为独立预后预测因素。  结论  晚期NSCLC治疗前胸部CT特征对预测克唑替尼治疗预后具有一定的价值。      

Association of smoking with tumor size at diagnosis in non-small cell lung cancer

Background

Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy.

Patients and methods

We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival.

Results

The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown = 121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months.The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p = 0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy.A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors.

Conclusions

The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy.     

Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer

The prognosis of non small cell lung cancer (NSCLC) has remained disappointing over the last decades even in localized stages. Numerous prognostic factors have been investigated which might select patients for additional treatment. The objective of the current study was to assess the prognostic significance of telomerase activity, serum anti-p53 antibodies (anti-p53a), c-erbB-2 and CEA in patients with NSCLC. The study included 60 patients with histological proven NSCLC besides 60 controls (30 smokers and 30 nonsmokers). Patients were divided into four stages according to their histopathology. All patients were subjected to; determination of telomerase activity by telomeric repeat amplification protocol (TRAP) assay in tumor tissue specimens and adjacent normal lung tissues, also, determination of preoperative serum anti-p53a, c-erbB-2 and CEA. Telomerase activity was detected in 40 of 60 (66.6%) of NSCLC tissue specimens using the TRAP assay. As regard the stages, telomerase activity was positive in 5 of 15 patients (33.3%) with stage I NSCLC, in 11 of 20 patients (55%) with stage II NSCLC, in 9 of 10 patients (90%) with stage III NSCLC and in all patients (100%) with stage IV NSCLC. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Telomerase activity was not detected in any normal lung tissue. The concentrations of serum anti-p53a, c-erbB-2, CEA were significantly higher in patients with NSCLC in comparison to the smoker and nonsmoker controls and their levels increased according to the stage of disease. Logistic regression test showed a relation between telomerase positivity and anti- p53a but no relation with c-erbB2, CEA. Telomerase activity was detected in most of NSCLC tissues; it was detected more frequently in advanced disease than early-stage disease. Anti-p53, c-erbB-2 and CEA were significantly higher in patients with NSCLC than controls and this increment was more evident in late stages of the disease. So, these biological markers might be useful predictors of prognosis. They may be helpful in defining groups of patients with NSCLC who could benefit from adjuvant treatments, also these markers can be used as therapeutic targets.     

非小细胞肺癌预后影响因素分析

目的:探讨非小细胞肺癌(NSCLC)患者的预后相关因素。方法:对2005年6月-2006年6月我院收治的162例非小细胞肺癌患者的临床、病理资料进行回顾性研究,采用Kaplan-Meier和COX回归方法分析评价各因素对预后的影响。结果:单因素分析表明KPS评分、手术与否、临床分期、治疗状况及治疗前血小板(PLT)、癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)的水平与NSCLC患者的预后有关。多因素分析表明,临床分期、治疗状况、血小板及血清癌胚抗原的水平是独立的预后影响因素。临床分期Ⅳ期、未治疗、PLT>300×109/L、CEA>5.0μg/L时,相对危险度(RR)分别为5.524、16.096、3.563、2.607。结论:治疗前血小板、血清CEA的水平、临床分期及治疗情况是NSCLC患者独立的预后影响因素。     

Prognostic factors in non-small cell lung cancer surgery.

AIMS: Complete surgical resection of primary tumours remains the treatment with the greatest likelihood for survival in early-stage non-small cell lung cancer (NSCLC). Although TNM stage is the most important prognostic parameter in NSCLC, additional parameters are required to explain the large variability in postoperative outcome. The present review aims at providing an overview of the currently known prognostic markers for postoperative outcome. METHODS: We performed an electronic literature search on the MEDLINE database to identify relevant studies describing the risk factors in NSCLC surgery. The references reported in all the identified studies were used for completion of the literature search. RESULTS: Poor pulmonary function, cardiovascular disease, male gender, advanced age, TNM stage, non-squamous cell histology, pneumonectomy, low hospital volume and little experience of the surgeon were identified as risk factors for postoperative outcome. However, with the exception of TNM stage and extent of resection, the literature demonstrates conflicting results on the prognostic power of most factors. The role of molecular biological factors, neoadjuvant treatment and adjuvant treatment is not well investigated yet. CONCLUSIONS: The advantage of knowing about the existence of comorbidity and prognostic risk factors may provide the clinician with the ability to identify poor prognostic patients and establish the most appropriate treatment strategy. The assessment of prognostic factors remains an area of active investigation and a promising field of research in optimising therapy of NSCLC patients.