Expression level of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) of patients with NSCLC as an early indicator to monitor the effects of postoperative adjuvant chemotherapy.

BACKGROUND: An early indicator for monitoring the effect of adjuvant treatment after lung cancer surgery is urgently needed. The study was to explore the effects of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) in NSCLC patients with postoperative adjuvant chemotherapy. METHODS: Two drugs (platinum-containing chemotherapeutics + platinum-free chemotherapeutics) first-line chemotherapy regimen were given after surgery. MRNA of EpCAM was detected. Chest computed tomography, head computed tomography and abdominal B-ultrasound were reviewed before the first and third chemotherapy. RESULTS: EpCAM in CTCs from peripheral blood between the recurrent group and the non-recurrent group at 1 day before surgery, first, second and third adjuvant chemotherapy were no significant differences (P>0.05). Only one day before the fourth adjuvant chemotherapy treatment, it showed significant difference between the recurrent group and the non-recurrent group (P=0.008). There was a significant difference between the time of imaging diagnosis of recurrence or metastasis and the time of monitoring the expression level of EpCAM in CTCs from peripheral blood (P<0.0001). CONCLUSIONS: EpCAM in CTCs from peripheral blood during postoperative adjuvant chemotherapy was related to recurrence or metastasis of NSCLC patients.

Comparative beneficiary effects of immunotherapy against chemotherapy in patients with advanced NSCLC: Meta-analysis and systematic review.

Lung cancer is the most commonly diagnosed cancer among men and it is the third ranked in women. There are two major types of lung cancer, namely, small cell lung cancer (SCLC), which accounts for ~20% of the cases, and non-small cell lung cancer (NSCLC), which is the most common. Chemotherapy and chemoradiotherapy have been used as the first-line therapies but suffer from lack of efficacy and also of several toxic adverse effects. Immunotherapeutic approaches including tumor antigen vaccination, monoclonal antibodies targeting checkpoint pathways and also activated immune cells are being developed and have been shown to be effective in treating NSCLC. Despite their promise, efficacy of several immunotherapies has not been consistent. We undertook this meta-analysis study to analyze results from clinical trials that compared efficacy and safety of immunotherapies with placebo or chemotherapy/radiotherapy in improving overall survival (OS) and progression-free survival (PFS) of NSCLC patients. Various databases were searched to identify randomized clinical studies examining the efficacy and safety of antibody- and vaccine-based immunotherapies in NSCLC patients in comparison to chemotherapy or chemoradiotherapy or placebo. Effects on OS and PFS and also adverse events have been compared. In accordance with the selection criteria, a total of 13 studies with 3,513 patients in immunotherapy and 3,072 patients in chemotherapy/placebo, were selected. PFS (odds ratio 1.81, 95% CI 1.36, 2.42; P<0.0001) and OS (P<0.0001) are found to be greatly improved by immunotherapies. Immunotherapy of NSCLC patients was also found to prevent several adverse effects and to improve daily living ability of the patients. The present meta-analysis strongly suggests that immunotherapy improves OS and PFS of patients with NSCLC.

Expression level of CRKL and AXL combined with exon 19 deletion in EGFR and ALK status confer differential prognosis of lung adenocarcinoma subtypes.

Non-small cell lung cancer (NSCLC) is a lethal cancer-related disease in population. Adenocarcinoma (AC) is subclassified into several subtypes based on the new classification by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society in 2011. Correlation between original expression of Crk-like (CRKL) and anaplastic lymphoma receptor tyrosine kinase in diverse histological components of AC and epidermal growth factor receptor (EGFR) or ALK status was evaluated by immunohistochemistry and sequencing in present study. A total of 106 cases, including 83 patients (78.3%) with mixed-type ACs, were assessed in the present study using eligible follow-up data. The ACs consisted of 32 acinar, 12 papillary, 5 mucinous, 11 micropapillary and 46 solid-predominant ACs. In total, 69.8% samples were composed of 2 or 3 histological components, with different expression levels of CRKL and AXL. ACs with EGFR mutation had a higher level of AXL expression compared with ACs without mutation (P=0.019). Multivariate survival analysis showed that AC subtypes and EGFR mutation subtypes were significantly associated with the progression-free survival (PFS) time. Acinar AC was the subtype with the most notable PFS time (30.6 months), which was significantly different from the PFS time of papillary, mucinous, micropapillary and solid-predominant ACs (hazard ratio, 0.4; 95% CI, 0.21-0.75; P=0.005). Among the ACs with exon 19 mutation, the median PFS time (28.8 months) of patients with a lower level of AXL protein expression was increased compared with the PFS time of patients with the L858R mutation and wild-type EGFR (9.1 months and 11 months, respectively; P=0.03), whereas no significant difference in ACs with an increased level of AXL expression. However, AC patients with higher level of CRKL expression had better PFS (28.8 months) than patients with the L858R mutation and wild-type EGFR (9.1 months and 11.3 months, respectively). Exon 19 deletion is an important status that is associated with an improved response to conventional chemotherapy. The identification of EGFR mutations combined with CRKL and AXL status may potentially alter the way that lung AC is treated.

The clinicopathological significance of hMLH1 hypermethylation in non-small-cell lung cancer: a meta-analysis and literature review.

The hMLH1 gene plays an essential role in DNA repair. Methylation of the hMLH1 gene is common in many types of cancer and can lead to the loss of hMLH1 expression. However, the association and clinicopathological significance between hMLH1 promoter hypermethylation and non-small-cell lung cancer (NSCLC) is elusive. Here, we investigated the correlation of hMLH1 promoter hypermethylation and NSCLC using 13 studies by comprising 1,056 lung cancer patients via a meta-analysis. We observed that 1) loss of hMLH1 protein expression was significantly associated with its promoter hypermethylation, 2) hMLH1 gene inactivation through hypermethylation contributed to the tumorigenesis of NSCLC, which could be a decisive factor for the pathogenesis of NSCLC due to its high occurrence in NSCLC tissues compared to normal lung tissues, 3) a correlation exists between histologic subtypes/disease stages (TNM I+II vs III+IV) and hypermethylation status of hMLH1 gene, and 4) NSCLC patients with hMLH1 hypermethylation and subsequent low expression levels of hMLH1 have a short overall survival period than those patients with normal expression of hMLH1 gene. hMLH1 mRNA predicts patient survival in lung cancer, and this was confirmed by using a public database. We then discussed the tumor suppressor function of hMLH1 and the clinicopathological significance of hMLH1 in NSCLC. We concluded that hMLH1 hypermethylation should be an early diagnostic marker for NSCLC and also a prognostic index for NSCLC. hMLH1 is an interesting therapeutic target in human lung cancers.

Clinicopathological significance and a potential drugtarget of RARß in non-small-cell lung carcinoma: a meta-analysis and a systematic review.

Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARß promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARß promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARß hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARß hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARß gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARß hypermethylation rate was not significantly correlated with stage of the disease and sex. RARß gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARß promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARß methylation contributes to the development of NSCLC, especially AC. RARß gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARß1' promoter.

Differential expression of CRKL and AXL genes in lung adenocarcinoma subtypes according to the epidermal growth factor receptor and anaplastic lymphoma kinase gene status.

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related mortality. Adenocarcinoma (AC) is the predominant histological type of NSCLC; however, AC consists of several subtypes. It has not yet been determined whether there is a correlation of CRKL and AXL expression with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene status in lung AC. We assayed exons 18 through 21 of the EGFR gene by direct sequencing; ALK rearrangement and the expression of CRKL and AXL were detected by immunostaining. A total of 212 cases of AC were included in this study, diagnosed using the novel classification system established by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society in 2011, including 69 acinar ACs, 17 lepidic predominant ACs (LPAs), 63 papillary, 14 mucinous, 17 micropapillary and 32 solid ACs. Of the 212 cases, 101 harbored EGFR mutations. The most common subtypes carrying delK745-S753 were papillary and acinar ACs. ALK rearrangement was found in 23 cases (11%) of lung ACs. Acinar and solid ACs were the most frequent subtypes with ALK aberrance, particularly in acinar ACs with cribriform structure (4/5 cases, 80%). The expression of CRKL was significantly different among the AC subtypes (P=0.01), with the highest and lowest expression levels of CRKL protein in papillary ACs and LPAs, respectively (P<0.05). AXL expression was also significantly different among the AC subtypes (P=0.002) and was correlated with lymph node infiltration in acinar ACs. ACs with EGFR mutations exhibited high levels of AXL protein expression compared to those without mutations (P<0.001). Acinar AC with cribriform structure is a distinct subtype that frequently harbors ALK rearrangement. The activation of AXL may be one of the factors contributing to the invasion of acinar and micropapillary ACs.

CD3+ CD4+ and CD3+ CD8+ lymphocyte subgroups and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer.

BACKGROUND: To explore the prevalence of lymphocyte subgroups CD3+ CD4+ and CD3+ CD8+ and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 40 patients with NSCLC were divided into different groups according to different clinical factors (TNM staging, pathological patterns and genders) for assessment of relations with CD3+ CD4+ and CD3+ CD8+ and the surface receptors NKG2D and NKG2A of T lymphocytes in peripheral blood by flow cytometry. RESULTS: Patients in the advanced group had evidently lower levels of CD3+ CD4+ but markedly higher levels of CD3+ CD8+ in peripheral blood than those with early lesions (p<0.05). In addition, NSCLC patients in the advanced group had obviously higher CD3+ CD4+ NKG2D and CD3+ CD8+ NKG2A expression rates but lower CD3+ CD4+ NKG2A and CD3+ CD8+ NKG2D expression rates (p<0.05). However, there were no significant differences between NSCLC patients with different genders and pathological patterns in expression levels of lymphocyte subgroups CD3+ CD4+ and CD3+ CD8+ and their surface receptors NKG2D and NKG2A. CONCLUSIONS: Unbalanced expression of surface receptors NKG2D and NKG2A in CD3+ CD4+ and CD3+ CD8+ lymphocytes may be associated with a poor prognosis, greater malignancy and immunological evasion by advanced cancers, related to progression of lung cancer.

Pulmonary lobectomy combined with pulmonary arterioplasty by complete video-assisted thoracic surgery in patients with lung cancer.

OBJECTIVE: To explore the feasibility of pulmonary lobectomy combined with pulmonary arterioplasty by complete video-assisted thoracic surgery (VATS) in patients with lung cancer, and summarize its surgical methods. MATERIALS AND METHODS: Twenty-one patients with lung cancer in Beijing Chest Hospital Affiliated to Capital Medical University from Feb., 2010 to Jun., 2013 were selected, males and females accounting for 15 and 6 cases, respectively. Ten underwent right upper lobectomy, 5 right lower lobectomy, 4 left upper lobectomy (in which left upper sleeve lobectomy was conducted for 2) and 2 left lower lobectomy. At the same time, local resection of pulmonary arterioplasty was performed for 12 patients, and sleeve resection of pulmonary arterioplasty for 9. RESULTS: Twenty-one patients recovered well after surgery. Thoracic drainage tube was maintained for 3-8 days, with an average of 4.9 days, and hospital stays were 8-15 days, with an average of 11 days. There were no deaths in the perioperative period, and the complications like pulmonary embolism, bronchopleural fistula, chest infection and pulmonary atelectasis did not occur after surgery. CONCLUSIONS: Performance of pulmonary lobectomy and pulmonary arterioplasty together by complete VATS is a safe and effective surgical method, which can expand the indications of patients with lung cancer undergoing thoracoscopic pulmonary lobectomy, and make more patients profit from such minimally invasive treatment.

[Video-assisted thoracoscopic surgery bronchial sleeve lobectomy for lung cancer].

OBJECTIVE: To discuss the feasibility of video-assisted thoracoscopic surgery(VATS) bronchial sleeve lobectomy for NSCLC,and to describe this treatment method and the major Indications. METHOD: Between September 2010 and December 2012, 10 patients in our hospital underwent VATS bronchial sleeve lobectomy.The patients were one female and nine males.Included 3 cases on the right upper lobe, 3 cases on the right lower lobe, 1 case on the right middle lobe, 2 cases on the left upper lobe, 1 case on the left lower lobe.2 cases underwent VATS bronchial sleeve lobectomy and sleeve resection of the pulmonary artery. RESULTS: 10 cases were finished by Video-Assisted Thoracoscopic Surgery.They all recovered well.No patient showed bronchopleural fistula, empyema and atelectasis.There was no perioperative death. CONCLUSIONS: Video-assisted thoracoscopic surgery (VATS) lobectomy including bronchial sleeve lobectomy is therefore considered to be a feasible surgical modality for the treatment of patients with NSCLC.

[Impact of TNM staging and treatment mode on the prognosis of non-small cell lung cancer].

OBJECTIVE: To study the impact of TNM staging and combined treatment mode on the survival of non-small cell lung cancer (NSCLC) patients. METHODS: From January 1997 to December 2002, 987 NSCLC patients were surgically treated in this hospital. Of those, 574 received combined modality therapy (surgery + chemotherapy/radiotherapy), while 413 underwent operation alone. Their clinicopathological data were retrospectively analyzed. RESULTS: The 1-, 3-, 5-, and 10-year overall survival rates were 87.7%, 57.5%, 54.6% and 54.5%, respectively, for the whole group, which were 90.6%, 57.5%, 54.3% and 54.1% for the combined therapy group versus 83.8%, 57.6%, 55.2% and 55.2% for the group treated by surgical resection alone. The 1-year survival rate of the combined therapy group was significantly higher than that of the surgical resection alone group (90.6% vs. 83.8%) (P<0.01). With regard to the T factor, 5-year survival rate of the combined therapy group (surgery + radiotherapy) was higher than that of surgery alone group, especially in T4 cases (43.6% vs. 12.7%), with a significant difference between them (P<0. 05). As for the N factor, the 1-year survival rate of NO patients in the combined therapy group (surgery + chemotherapy/radiotherapy) was significantly higher than that of surgery alone group (94.4%, 97.9% vs. 90.0%) (P<0.05). The 1-year survival rate of N1 patients in the combined therapy group (surgery + chemotherapy or + chemotherapy and radiotherapy) was 91.7% and 100% versus 82.9% in the surgery alone group (P<0.01); The 1- and 3-year survival rates of N2 patients in the combined modality therapy group (surgery + chemotherapy) were 82.1% and 37.3%, while those of the surgery alone group were 69.4% and 26.5%, respectively, with a significant difference (P<0.05, P<0.01). All the severity of primary tumor, distance of lymph node involvement, and distant tumor metastasis significantly worsen the prognosis of the patients. CONCLUSION: The prognosis in NSCLC patients treated with combined modality therapy (surgery + chemotherapy/radiotherapy) is better than that with surgery alone. The larger the original tumor and the farther the lymph node and tumor metastases, the worse the prognosis is for NSCLC patients.

[Surgical treatment of 133 cases of multi-drug-resistant pulmonary tuberculosis].

OBJECTIVE: To evaluate the clinical significance of pulmonary resection for multi-drug-resistant pulmonary tuberculosis. METHODS: The clinical data were retrospectively reviewed for patients with multi-drug-resistant pulmonary tuberculosis for which surgical resection of the lung was undertaken. RESULTS: From January 1980 to December 2007, 1188 patients with pulmonary tuberculosis, including 133 multi-drug resistant cases, underwent pulmonary resection in Beijing Chest Hospital. Surgical procedures included pneumonectomy in 45, pulmonary lobectomy in 73 (including sleeve resection of the bronchus in 5), pleuropneumonectomy in 13, segment resection in 1, and wedge resection in 1 cases. Preoperative and postoperative antituberculosis chemotherapy was given for no less than 6 months and 6 to 18 months, respectively. Two cases died of perioperative respiratory failure, and 1 died of internal bleeding, the mortality rate being 2.3% (3/133). The incidence of postoperative complications was 17.3% (23/133), including 9 cases with stump fistula of bronchus. Follow-up lasted for 6 months to 15 years (average 52 months), and medical treatment lasted for 6 - 18 months. After follow-up, the sputum negative conversion rate was 90.2% (101/112). CONCLUSIONS: Pulmonary resection is an effective approach to multi-drug resistant pulmonary tuberculosis with long-term sputum positivity of limited local lesions, or negative sputum of local lesions but failure to antituberculosis chemotherapy for at least 3 months.

[Different treatment modalities of patients with stage III lung cancer].

OBJECTIVE: In order to improve the survival-rates and study the long-term therapeutic effect of stage III lung cancer patients with different treatment modalities. METHODS: From 1995 to 2004, 1921 patients of stage III lung cancer treated at our hospital were retrospectively analyzed to compare the long-term therapeutic effect of different treatment modalities. There were 606 cases in the combined therapy group (mainly surgical with combined treatment of chemotherapy & radiotherapy), 317 cases in the surgery alone group and 998 cases in the non-surgical group. The 1, 3, 5-year survival rates of these three groups were 66.0% (400/606) vs. 62.7% (199/317) vs. 51.2% (511/998), 32.34% (196/606) vs. 21.45% (68/317) vs. 8.15% (81/998), 19.31% (117/606) vs. 13.2% (42/317) vs. 4.2% (42/998) respectively. In comparison, 1, 3, 5-year survival rates of the combined therapy group was higher than the surgery alone and non-surgical groups; Significant differences in 1-year survival rates were found between the combined therapy group and the surgery alone group or the non-surgical group (P < 0.01) and significant differences in 3, 5-year survival rates among these three groups. CONCLUSION: The combined therapy of radical resection with chemotherapy and radiotherapy is the best treatment modality for stage III lung cancer.

[Second-line Hycamtin in the treatment of lung cancer].

OBJECTIVE: To discuss the therapeutic effect and toxicity of second line Hycamtin for lung cancer patients. METHODS: Ten of these 21 patients had been treated with operation. All these 21 patients received second line Hycamtin treatment; given at the dose of 1.2 mg/m(2) per day, four consecutive days as one cycle and 21 days as one course. A total of 1 - 4 courses were given according to the patient's tolerance. Four of these 21 patients also received combination of cisplatin. RESULTS: Among the 13 un-operated patients, two patients showed CR, six showed PR, three SD and two PD, giving an effective rate of 62%. Among the 8 operated patients, seven showed SD but one developed distant metastasis. The 1-year survival rate was 88%. TOXICITY: leukopenia I-II degree 14 (66.7%), leukopenia III-IV degree 5 (23.8%), thrombocytopenia III-IV degree 1 (4.8%) and one patient died of high fever and neutocytopenia. Nausea 8 (38.1%), vomiting 3 (14.3%) and diarrhea 2 (9.5%) alopecia 4 (19.1%). Were the other side-effects. CONCLUSION: Hycamtin is indicated for second line therapy for lung cancer giving tolerable toxicity.