Expert Consensus on Prevention and Treatment of COVID-19 Infection in Patients with Lung Cancer

Corona virus disease 2019(COVID-19)infection has become a major public health issue affecting human health.The main goal of epidemic prevention and control at the current stage in China is to“protect people’s health and prevent severe cases”.Patients with lung cancer who receive antitumor therapy have low immunity,and the risk of severe illness and death once infected is much higher than healthy people,so they are vulnerable to COVID-19 infection.At present,less attention has been paid to the prevention and treatment of COVID-19 infection in patients with lung cancer in domestic guidelines and consensus.Based on the published data in China and abroad,we proposed recommendations and formed expert consensus on the vaccination of COVID-19,the use of neutralizing antibodies and small molecule antiviral drugs for patients with lung cancer,for physician’s reference.

基于HRCT影像组学、临床特征与SUV_(max)的联合模型列线图预测cT_(1)N_(0)M_(0)期肺腺癌脏层胸膜浸润的价值

目的:探讨基于HRCT图像的影像组学、临床特征与最大标准化摄取值(SUV_(max))的列线图预测cT_(1)N_(0)M_(0)期肺腺癌脏层胸膜浸润(VPI)的价值。方法:回顾性分析经手术病理证实为cT_(1)N_(0)M_(0)期肺腺癌,并行HRCT和18F-FDG PET/CT扫描的155例患者,共157个病灶,按7∶3的比例随机分为训练集(110个病灶)和测试集(47个病灶)。从CT图像中共提取1158个影像组学特征。应用影像组学分析计算影像组学评分,并结合临床特征、SUV_(max)和CT特征,构建预测胸膜浸润的联合模型,以列线图进行可视化。采用ROC曲线、校准曲线和决策曲线对模型性能进行评估。结果:联合模型的多因素逻辑回归分析结果显示,影像组学评分(OR=3.14,P=0.002)、CT观测结节与胸膜的关系(OR=2.79,P<0.001)、SUV_(max)(OR=1.31,P=0.035)为肺腺癌VPI的独立预测因子。联合预测模型在测试集的AUC值、准确率、敏感度、特异度分别为0.869、0.787、0.909、0.750,明显高于临床模型和单独的影像组学评分。结论:基于HRCT图像的影像组学、临床特征与SUV_(max)的联合模型列线图可准确预测cT_(1)N_(0)M_(0)期肺腺癌患者VPI情况,有望成为临床术前评估肺腺癌VPI的可靠工具。

The Clinical Usefulness of ^(99m)Tc-Tetrofosmin Scintigraphy in the Diagnosis of Lung Neoplasmas and Mediastinal Lymphoid Node Involvement

In order to investigate the clinical significance of 99mTc-Tetrofosmin （TF） scintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmo- nary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target （T/N） ratio between the lung cancer group and the benign lesion group （P〈0.001）. Moreover, in the lung cancer group, T/N ratio in tomographies was signifi- cantly higher than that in planar images （P〈0.01）. The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas （P〈0.05 and P〈0.01 respectively）, so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinal lymphoid node metastasis （P〈0.05）. It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas （P〈0.05）, and 2 h washout rate （WR） of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas （P〈0.05）. In conclusion, 99mTc-TF scintigraphy showed a favorable diag- nostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.

Application of GLAD-PCR Assay for Study on DNA Methylation in Regulatory Regions of Some Tumor-Suppressor Genes in Lung Cancer

Hypermethylation of the gene regulatory regions are common for many cancer diseases. In this work we applied GLAD-PCR assay for identificating of the aberrantly methylated RCGY sites in the regulatory regions of some downregulated genes in tissue samples of lung cancer(LC). This list includes EFEMP1, EPHA5, HOXA5, HOXA9, LHX1, MYF6, NID2, OTX1, PAX9, RARB, RASSF1 A, RXRG, SIX6, SKOR1 and TERT genes. The results of DNA samples from 40 cancer and 25 normal lung tissues showed a good diagnostic potential of selected RCGY sites in regulatory regions of MYF6, SIX6, RXRG, LHX1, RASSF1 A and TERT genes with relatively high sensitivity(80.0 %) and specificity(88.0 %) of LC detection in tumor DNA.

N2 disease in non-small cell lung cancer patients,diagnosis and evaluation:a Turkish chest surgeon s perspective

Mediastinal or N2 disease is the most important factor in selecting the optimal treatment strategy in patients without distant metastasis.A direct surgical resection has not generally been accepted as a treatment modality in whom mediastinal nodal involvement is demonstrated.Patients with lung cancer can be diagnosed as clinical N2 disease based on CT and PET-CT characteristics of the mediastinum and the clinical presentation.Invasive diagnostic modalities used in the detection of N2 disease are:mediastinoscopy,endoesophageal ultrasound guided biopsy(EUS),transbronchial needle aspiration(TBNA),endobronchial ultrasound guided biopsy(EBUS),video-assisted thoracoscopic surgery(VATS),and mediastinotomy/extended mediastinoscopy.In this article,the author discusses about invasive and noninvasive techniques on the evaluation of mediastinal disease and presents his experience on this topic.

The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant metastases.Lung metastasis is one of the most important causes of death for patients with NPC.Solitary metastatic lung tumor from NPC is a distinctive group associated with a better survival.This study was to find a more effective treatment modality and prognostic factors for the group.Methods:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively analyzed.Survival rate was calculated by the Kaplan-Meier method.The difference of survival between the patients treated by different modalities was evaluated by the log-rank test.The Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were conducted.Results:The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy +/-chemotherapy group, and 96.4% in operation +/-chemotherapy group (P<0.01).The most promising progression-free survival (PFS) and overall survival (OS) were obtained with operation +/-chemotherapy and followed by radiotherapy +/-chemotherapy.Both of them showed much better efficacy than chemotherapy (P<0.001).The Cox multivariate analysis showed that recurrent distant metastases and/or relapse of NPC affected the survival (OR=2.087, 95% CI=1.277-3.410, P=0.003).The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic factors.Conclusions:Operation +/-chemotherapy and radiotherapy +/-chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and OS.Chemotherapy is recommended for patients with higher T stage of NPC, size of metastatic tumor ≥3 cm, pulmonary hilar and/or mediastinal lymph node metastasis.

Surgical Therapeutic Strategy for Non-small Cell Lung Cancer with Mediastinal Lymph Node Metastasis (N2)

Background and objective Approximately 30% of patients who are diagnosed with non-small cell lung cancer (NSCLC) are classified as N2 on the basis of metastasis to the mediastinal lymph nodes. The effectiveness of surgery for these patients remains controversial. Although surgeries in recent years are proved to be effective to some extent,yet due to many reasons,5-year survival rate after surgery varies greatly from patient to patient. Thus it is necessary to select patients who have a high probability of being be cured through an operation,who are suitable to receive surgery and the best surgical methods so as to figure out the conditions under which surgical treatment can be chosen and the factors that may influence prognosis. Methods 165 out of 173 patients with N2 NSCLC were treated with surgery in our department from January 1999 to May 2003,among whom 130 were male,43 female and the sex ratio was 3:1,average age 53,ranging from 29 to 79. The database covers the patients’ complete medical history including the information of their age,sex,location and size of tumor,date of operation,surgical methods,histologic diagnosis,clinical stage,post-operative TNM stage,neoadjuvant treatment and chemoradiotherapy. The methods of clinical stage verification include chest X-ray,chest CT,PET,mediastinoscopy,bronchoscope (+?),brain CT or MRI,abdominal B ultrasound (or CT),and bone ECT. The pathological classification was based on the international standard for lung cancer (UICC 1997). Survival time was analyzed from the operation date to May 2008 with the aid of SPSS (Statistical Package for the Social Sciences) program. Kaplan-Meier survival analysis,Log-rank test and Cox multiplicity were adopted respectively to obtain patients’ survival curve,survival rate and the impact possible factors may have on their survival rate. Results The median survival time was 22 months,with 3-year survival rate reaching 28.1% and 5-year survival rate reaching 19.0%. Age,sex,different histological classification and postoperative chemoradiotherapy seem to have no correlation with 5-year survival rate. In all N2 subtypes,5-year survival rate is remarkably higher for unexpected N2 discovered at thoractomy and proven N2 stage before preoperative work-up and receive a mediastinal down-staging after induction therapy (P<0.01),reaching 30.4% and 27.3% respectively. 5-year survival rate for single station lymph node metastasis were 27.8%,much higher compared with 9.3% for multiple stations (P<0.001). Induction therapy which downstages proven N2 in 73.3% patients gains them the opportunity of surgery. The 5-year survival rate were 23.6% and 13.0% for patients who had complete resection and those who had incomplete resection (P<0.001). Patients who underwent lobectomy (23.2%) have higher survival rate,less incidence rate of complication and mortality rate,compared with pneumonectomy (14.8%) (P<0.01). T4 patients has a 5-year survival rate as low as 11.1%,much less than T1 (31.5%) and T2 (24.3%) patients (P=0.01). It is noted through Cox analysis that completeness of resection,number of positive lymph node stations and primary T status have significant correlativity with 5-year survival rate. Conclusion It is suggested that surgery (lobectomy preferentially) is the best solution for T1 and T2 with primary tumor have not invaded pleura or the distance to carina of trachea no less than 2 cm,unexpected N2 discovered at thoractomy when a complete resection can be applied,and proven N2 discovered during preoperative work-up and is down-staged after induction therapy. Surgical treatment is the best option,lobectomy should be prioritized in operational methods since ite rate of complication and morality are lower than that of pneumonectomy. Patients’ survival time will not benefit from surgery if they are with lymph nodes metastasis of multiple stations (Bulky N2 included) and T4 which can be partially removed. Neoadjuvant chemotherapy increases long-term survival rate of those with N2 proven prior to surgery. However,postoperative radiotherapy decreases local recurrence rate but does not contribute to patients’ long-term survival rate.

Expression of Livin in tissues of lung cancer and its correlation with the expression of caspase-3

Objective: To study the expressions of two isoforms of Livin in tissues of lung cancer and their relations to histological types and chemotherapy, and to study their correlations to the expression of caspase-3 as well. Methods: Ex-pressions of Livin isoforms α, β and caspase-3 were detected by reverse transcription polymerase chain reaction (RT-PCR) assay in lung cancer tissues as well as in controls. Results: Livin isoforms α and β were expressed in 12 of 27, and 19 of 27 lung cancer tissues respectively, much more than those in lung para-cancerous [both were (0/6)] or benign disease lung tissues (0/12, 1/12; P < 0.01 and P < 0.01). Moreover, they were detected in 7/14, 9 /14 lung adenocarcinomas and 4/12, 9/12 squamocellular and large cell carcinomas, respectively, and both showed expressions in one small cell carcinoma. The levels of these two isoforms in lung cancer were significantly higher than those in controls by Gel imaging system (P < 0.05 and P < 0.05), the former was higher in adenocarcinoma than that in squamocellular carcinoma (P < 0.05), while the latter was the same in both (P > 0.05). Meanwhile, the levels of caspase-3 in lung cancer were significantly lower than those in controls, and it was suggested to be negatively associated with either each of two isoforms or their sum (P < 0.05, P < 0.01 and P < 0.01). Two isoforms of Livin expression seemed to increase after chemotherapy but not related to clinical stages (P > 0.05). Conclusion: Two isoforms of Livin are differently expressed in different histological types of lung cancer and may contribute to corresponding cancerous development; the levels of Livin are negatively associated with those of caspase-3, this may be due to the fact that Livin could resist against apoptosis; high expression of Livin seems to be related to chemotherapy but not clinical stages.

Lung Cancer Survival Improvement through Surgical Intervention in PUMCH Hospital

客观：在最后 15 年期间在 PUMC 医院里在外科的干预以后调查并且评估肺癌症幸存的改进。方法：从 1989 年 1 月到 2003 年 12 月， 1574 个肺癌症案例经历了外科疗法并且列在后面起来。在这个系列的所有情况根据时间时期被划分成二个组：组织 A (1999-2003 ) 并且组织 B (1989-1998 ) 。在幸存的差别在组 A 之间评价， B 被比较。结果：在组 A 的 Themorbidity 和死亡与组 B 相比显著地被减少(11.2%vs.19.2% ， 1.06% 对 1.93% ，分别地) 。然而， 3 年、 5 年的幸存率分别地从 42.35% ～ 56.07% ，并且从 28.46% ～ 38.99% 被增加。在幸存的重要改进也与阶段Ⅲ B 和Ⅳ与阶段Ⅰ，Ⅱ和Ⅲ A 在病人，然而并非在那些被观察，有叶切除术的病人比那些收到的 exploratorythoracotomy，有限切除术，肺切除术和袖口式切除术有更令人满意的结果。结论：叶切除术正系统的纵隔淋巴节点解剖为将切除成为了标准模式有能力的肺癌症。与淋巴一起的完全的切除术的联合节的解剖，和手术后的辅助化疗基于 platinum/3rd 产生化疗药， preliminarily 被认为正当，在长期的幸存为有效改进证明一条重要途径 ofnon 小的房间肺癌。

THE CLINICAL COURSE AND TREATMENT RESULTS OF LUNG METASTASES FROM BREAST CANCER

Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table Results: The median time from initial treatment of primary tumor to lung metastases was 22 months Sites of common consecutive metastases were lung, liver and bone The overall response rate was 48% with a CR rate of 15% Compared to non DDP encompassing regimen, the CR rate was higher in DDP based chemotherapy (7% versus 21%, P <0 05) with a longer median survival time (MST) The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P <0 01) The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy ( P >0 05) No difference in MST was observed between patients receiving anthracycline and non anthracycline encompassing regimens The 1 , 3 , 5 , and 10 year survival rate was 77%, 22%, 11%, and 10%, respectively Conclusion: Size of primary tumor, the length of disease free interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases Combination chemotherapy, especially DDP based chemotherapy may prolong survival time of patients with lung metastases from breast cancer

Radioenhancing effect of earthworm capsule medication on radiotherapy in the treatment of patients with carcinoma of esophagus or lung

Earthworm capsule is an extract from earthworm made in our laboratory.From1986 to 1989,486 patients with carcinoma of esophagus or lung were randomly divided into 2groups,one group received radiotherapy alone(control group)and the other radiotherapycombined with earthworm capsules(treatment group).All cases were diagnosedpathologically or cytologically.In a two-month treatment course,earthworm capsuleswere given orally twice a day,2～3 capsules each time,each capsule containing 60 mg ofthe extract.Compared with the control group,the CR(complete remission)rate andCR+PR(partial remission)rate in patients with carcinoma of esophagus treated byradiotherapy in combination with earthworm capsule increased 9.7%(P【0.01) and 9.6%(P【0.05),while in patients with carcinoma of lung,they increased 10.6%(P【0.05)and13.5%(P【0.05),respectively.The earthworm capsule caused irritation in the alimentarytract,the patients displaying slight nausea and vomiting(16.7% in thecombination treatment group and 10.0% in the control group).However,these side ef-fects could be alleviated when capsules were taken after meal or with honey concomitantly.No deleterious effects on the heart,liver,kidney,skin,hematopoietic or nervous systemwere seen.

Prospective Analysis on Survival Outcomes of Nonsmall Cell Lung Cancer Stages over Ⅲb Treated with HangAm-Dan

Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.Keywords Lung neoplasms; HangAm-Dan; Oriental medicine; Overall survival rate; Cancer; Herb Abstract Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.

Is there a role for surgery in stage ⅢA-N2 non-small cell lung cancer?

The role of surgery in stage ⅢA-N2 non-small cell lung cancer(NSCLC) remains controversial.Most important prognostic factors are mediastinal downstaging and complete surgical resection.Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive,invasive and alternative or minimally invasive techniques.In contrast to imaging or functional studies,remediastinoscopy provides pathological evidence of response after induction therapy.Although techn...

Combined Double Sleeve Lobectomy and Superior Vena Cava Resection for Non-small Cell Lung Cancer with Persistent Left Superior Vena Cava

A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department.Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor.Chest contrast computed tomography revealed the tumor invaded right pulmonary artery,superior vena cava,and the persistant left superior vena cava flowed into the coronary sinus.The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava(SVC)utilizing ringed polytetrafluoroethylene graft.To the best of our knowledge,this was the first report of complete resection of locally advanced lung cancer involving superior vena cava,right pulmonary artery trunk and main bronchus with persistant left superior vena cava.

SIGNIFICANCE OF ELECTRON MICROSCOPIC EXAMINATION IN THE DIAGNOSIS OF PULMONARY NEOPLASMS

The significance of electronic microscopc examination(EM) in the diagnosis of pulmonary neoplasms was evaIuated in 40 cases of Patients with different kinds of Pulmonary neoplasms.In 27 of the 40 cases,final diagnoses were made by light microscope(LM) examination,while in the remaining 13 cases,LM faded to reach definite diagnoses which were established with the help of EM.By analyzing our data,we conclude that in the following situations,EM helps meet in the diagnosis of pulmonary neoplasm:1.diagnosis of neuroendocrinal carcinomas of the lung;2.diagnosis of some rare pulmonary neoplasm;3.documentation of the histologic origins of the matastatic pulmonary neoplasms and 4.differentiation of malignant mesothelioma with pleural metastasis of Pulmonary adenocarcinoma.

Mediastinal lymphadenectomy influences postoperative immune response after lung cancer surgery

The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.The study group consisted of 11 patients with cancer of the right lung(Group 1).The control group consisted of 12 patients with left lung cancer(Group 2).In patients with right lung cancer systematic lymphadenectomy,while in patients with left lung cancer systematic sampling was performed.Serum IL-6 and IL-1ra concentration was measured before and after surgery,and on postoperative day 1,3,and 7,as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1,by ELISA test.Peripheral blood lymphocyte(PBL) count was measured with flow cytometry.Time of surgery was higher in patients with right than left lung cancer(154.1±31.29) vs(119.6±24.81) min;P=0.008) .The number of resected mediastinal lymph nodes was higher in patients with right than left lung cancer(27.6±7.6) vs(11.1 ±8.1);P=0.00006) .Postoperative decrease of PBL was significantly higher in group 1 than 2(1.25±0.37) vs(1.75 ±0.64) ×103/μL;P=0.04) .No significant differences were found in serum,pleural fluid and sputum concentration of IL-6 and IL -1ra between groups.Negative correlation between concentration of these cytokines in pleural fluid and number of resected mediastinal lymph nodes was found(Spearman test for IL-6:r=-0.723;P<0.001;for IL-1ra:r=-0.768;P<0.001).Number of "positive" N2 lymph nodes did not correlate with pleural fluid concentration of cytokines.Systematic lymphadenectomy of the mediastinum causes immunosuppression,as measured by decreased count of PBL and a negative correlation between number of resected mediastinal lymph nodes and concentration of cytokines in pleural fluid.

Environmental tobacco smoke exposure and lung cancer:A systematic review

AIM:To review evidence relating passive smoking to lung cancer risk in never smokers,considering various major sources of bias.METHODS:Epidemiological prospective or case-control studies were identified which provide estimates of relative risk(RR) and 95% CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke(ETS):The spouse; household; workplace; childhood; travel; social and other; and total.A wide range of study details were entered into a database,and the RRs for each study,including descriptions of the comparisons made,were entered into a linked database.RRs were derived where necessary.Results were entered,where available,for all lung cancer,and for squamous cell cancer and adenocarcinoma."Most adjusted" results were entered based on results available,adjusted for the greatest number of potential confounding variables."Least adjusted" results were also entered,with a preference for results adjusted at least for age for prospective studies.A pre-planned series of fixed-effects and random-effects meta-analyses were conducted.Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex,and results for childhood exposure given by source of ETS exposure.For spousal exposure,more extensive analyses provide results by various aspects of study design and definition of the RR.For smoking by the husband(or nearest equivalent),additional analyses were carried out both for overall risk,and for risk per 10 cigarettes per day smoked by the husband.These adjusted for uncontrolled confounding by four factors(fruit,vegetable and dietary fat consumption,and education),and corrected for misclassification of smoking status of the wife.For the confounding adjustment,estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure,and on the correlations between the factors.The bias due to misclassification was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere,and that those who deny smoking have the same risk as those who admit it.This approach,justified in previous work,balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS:One hundred and two studies were identified for inclusion,published in 1981 onwards,45 in Asia,31 in North America,21 in Europe,and five elsewhere.Eightyfive were of case-control design and 17 were prospective.Significant(P < 0.05) associations were noted,with random-effects of(RR=1.22,95%CI:1.14-1.31,n=93) for smoking by the husband(RR=1.14,95%CI:1.01-1.29,n=45) for smoking by the wife(RR=1.22,95%CI:1.15-1.30,n=47) for workplace exposure(RR=1.15,95%CI:1.02-1.29,n=41) for childhood exposure,and(RR=1.31,95%CI:1.19-1.45,n=48) for total exposure.No significant association was seen for ETS exposure in travel(RR=1.34,95%CI:0.94-1.93,n=8) or in social situations(RR=1.01,95%CI:0.82-1.24,n=15).A significant negative association(RR=0.78,95%CI:0.64-0.94,n=8) was seen for ETS exposure in childhood,specifically from the parents.Significant associations were also seen for spousal smoking for both squamous cell carcinoma(RR=1.44,95%CI:1.15-1.80,n=24) and adenocarcinoma(RR=1.33,95%CI:1.17-1.51,n=30).Results generally showed marked heterogeneity between studies.For smoking by either the husband or wife,where 119 RR estimates gave an overall estimate of(RR=1.21,95%CI:1.14-1.29),the heterogeneity was highly significant(P < 0.001),with evidence that the largest RRs were seen in studies published in 1981-89,in small studies(1-49 cases),and for estimates unadjusted by age.For smoking by the husband,the additional analyses showed that adjustment for the four factors reduced the overall(RR=1.22,95%CI:1.14-1.31) based on 93 estimates to(RR=1.14,95%CI:1.06-1.22),implying bias due to uncontrolled confounding of 7%.Further correction for misclassification reduced the estimate to a marginally non-significant(RR=1.08,95%CI:0.999-1.16).In the fully adjusted and corrected analyses,there was evidence of an increase in Asia(RR=1.18,95%CI:1.07-1.30,n=44),but not in other regions(RR=0.96,95%CI:0.86-1.07,n=49).Studies published in the 1980's,studies providing dose-response data,and studies only providing results unadjusted for age showed elevated RRs,but later published studies,studies not providing dose-response data,and studies adjusting for age did not.The pattern of results for RRs per 10 cigs/d was similar,with no significant association in the adjusted and corrected results(RR=1.03,95%CI:0.994-1.07).CONCLUSION:Most,if not all,of the ETS/lung cancer association can be explained by confounding adjustment and misclassification correction.Any causal relationship is not convincingly demonstrated.

Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer

Objective The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in advanced non-small cell lung cancer(NSCLC) has not yet been established.The aim of the current study was to identify whether the 2 TKI treatment or chemotherapy(paclitaxel-containing or non-paclitaxel regimen) is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs. Methods Seventy-two advanced NSCLC patients who had accepted 2 TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1,2004 to January 31,2010 at the Sun Yat-sen University Cancer Center were enrolled.The primary endpoint[2 progression-free survival(PFS)]and the second endpoint[overall survival(OS)]were compared among the 2 TKI and chemotherapy groups as well as their subgroups. Results(1) Twenty-one patients were treated with 2 TKIs,and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment.There was nonsignificant difference in the responses(P=0.900)[2 PFS(P=0.833) and OS(P=0.369)] between the 2 TKI and chemotherapy groups.(2) In the 2 TKI group,9 patients exhibited PFS>7 months.The initial TKI treatment group exhibited a longer 2 PFS than the other 12 patients with an initial PFS<7 months(7 months vs.2 months,P=0.019).However, these groups had nonsignificantly different OS(P=0.369).(3) In the chemotherapy group,patients with PFS<5 months exhibited longer 2 PFS than those with PFS > 5 months in the initial TKI treatment(3 months vs.2 months,P=0.039).(4) In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2 PFS than those treated with non-paclitaxel regimen(5 months vs.2.3 months,P=0.043). Conclusions Patients with PFS>7 months or <5 months under the initial TKI treatment potentially benefit from the 2 TKI treatment or chemotherapy immediately after failure of the non-first line TKIs.The paclitaxel-containing regimen may improve the 2 PFS. However,more patient samples are urgently needed to validate these findings.

Bioinformatics Identification of ZNFs/LINC00520/miR-181d/BCL2 Axis as a Novel Network in Cisplatin-Resistant Lung Adenocarcinoma Cells

Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, therefore, novel strategies to reverse chemoresistance by regulating autophagy are desperately needed. Methods: The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between A549 and A549/DDP cell lines were identified using the limma package in R, after gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. By combining Autophagy-Related Genes (ARGs) from Human Autophagy Database (HADb), the interactions lncRNA-miRNAs and the interactions miRNAs-mRNAs respectively predicted by miRcode and miRDB/Targetscan database, the autophagy-related ceRNA network was constructed. Then, extraction of ceRNA subnetwork and Cox regression analyses were performed. A prognosis-related ceRNA subnetwork was constructed, and the upstream Transcription Factors (TFs) regulating lncRNAs were predicted by the JASPAR database. Finally, the expression patterns of candidate genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Results: A total of 3179 DEmRNAs, 180 DEmiRNAs, and 160 DElncRNAs were identified, and 35 DEmRNAs were contained in the HADb. Based on the ceRNA hypothesis, we established a ceRNA network, including 10 autophagy-related DEmRNAs, 9 DEmiRNAs, and 14 DElncRNAs. Then, LINC00520, miR-181d, and BCL2 were identified to construct a risk score model, which was confirmed to be a well-predicting prognostic factor. Furthermore, 5 TF ZNF family members were predicted to regulate LINC00520, whereas the RT-PCR results showed that the 5 ZNFs were consistent with the bioinformatics analysis. Finally, a ZNF regulatory LINC00520/miR-181d/BCL2 ceRNA subnetwork was constructed. Conclusions: An ZNFs/LINC00520/miR-181d/BCL2 axis as a novel network in DDP-resistant LUAD has been constructed successfully, which may provide potential therapeutic targets for LUAD.