Guowei Che

The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

BackgroundTumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patients survival time.MethodsNinety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patients survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).ResultsThe numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patients survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patients survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patients survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patients survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patients survival time.ConclusionsThe number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patients survival time than counting mature dendritic cells or cytotoxic T cells.

A new concept of endoscopic lung cancer resection: Single-direction thoracoscopic lobectomy

Although video-assisted thoracoscopic surgery was introduced in the early 1990s, its use in the treatment of lung cancer has been limited. We examined the effectiveness of a simplified surgical method for thoracoscopic lobectomy in patients with lung cancer from May 2006 to October 2007. This novel single-direction thoracoscopic lobectomy was characterized by incisions convenient for the placement of instruments and the lobectomy proceeded progressively in a single direction from superficial to deep structures. The procedure was completed successfully in 26 of 28 patients, with no perioperative deaths. The average operation time was 135min (range, 100-200min), average blood loss was 125mL (range 10-500mL) and average number of lymph nodes dissected was 11.8 (range, 6-23). The average postoperative hospital stay was 7.4 days (range, 5-10 days). Single-direction thoracoscopic lobectomy is a simple, safe, and effective procedure for lobe resection with clear procedural steps. It overcomes the difficulty in manipulation of incomplete lung fissures and potentially extends the indications of thoracoscopic lobectomy.

Cardiopulmonary exercise testing screening and pre-operative pulmonary rehabilitation reduce postoperative complications and improve fast-track recovery after lung cancer surgery: A study for 342 cases.

An evaluation of cardiopulmonary exercise testing (CPET) screening and pre‐operative pulmonary rehabilitation in reducing postoperative complications and improving fast‐track recovery in high‐risk patients who undergo resection for lung cancer.

Giant congenital diaphragmatic hernia in an adult

Bochdalek hernia is the most common type of congenital diaphragmatic hernia. It appears frequently in infants but rarely in adults. We present the case of a 50-year-old female han patient with tremendous left-sided congenital posterolateral diaphragmatic hernia (Bochdalek hernia) who also has a pair of supernumerary breasts and pulmonary hypoplasia of the lower-left lobe. The patient had an experience of misdiagnosis and she was treated for bronchitis for one year until being admitted to our hospital. This case study emphasizes the rare presentation of Bochdalek hernia in adults and the necessity of high clinical attention to similar cases.

[Establishment and their biological characteristics of clonal cell subpopulations (NL9980 and L9981) from a human lung large cell carcinoma cell line (WCQH-9801)].

BACKGROUND To explore the possibility of separating and establishing clonal cell subpopulations with different metastatic phenotype from a human lung large cell carcinoma cell line (WCQH-9801), to identify the difference of biological and molecular biology between NL9980 and L9981 cell lines. METHODS Two sub-cell lines (NL9980 and L9981) were isolated and established from a human lung large cell carcinoma cell line (WCQH-9801) by the single cell cloning techniques. The RELP, mRNA and protein transcript expression were detected in NL9980 and L9981 cell lines by Southern blot, RT-PCR and Western blot. The biological characteristics of vivo and vitro were determined in NL9980 and L9981 cell lines by MTT, plate, Boyden chamber methods and animal models. RESULTS (1)Two sub-cell lines, NL9980 and L9981 which had different metastatic phenotype, were successfully isolated and established from a human lung large cell carcinoma cell line (WCQH-9801). (2)The L9981 cell line had LOH of nm23-H1 gene, deletion of mRNA and protein expression of nm23-H1, but the NL9980 cell line had neither LOH of nm23-H1 nor deletion of mRNA and protein expression of nm23-H1. (3)The proliferation, clone formation and vitro invastion of L9981 cell line were significantly higher than those of NL9980 cell line. (4)The tumorigenicity and lung metastatic rate in nude mouse of L9981 cell line were remarkably higher than those of NL9980. (5) No significant difference of the chromosome number was observed between NL9980 and L9981 cell lines. CONCLUSIONS (1)NL9980 and L9981 cell lines established from a human lung large cell carcinoma cell line have different biological and molecular characteristics. (2)The high invsaion and metastasis ability of L9981 cell line might be related to the LOH of nm23-H1 gene.

Study on the association between genetic polymorphism of CYP2E1, GSTM1 and susceptibility of lung cancer

BACKGROUND Lung cancer is the leading cause of malignant tumor death among Chinese population. It has been known that the development of lung cancer may be associated with genetic po-lymorphism of some lung cancer related genes. The aim of this study is to evaluate the relationship between genetic polymorphism of metabolizing enzymes and susceptibility of lung cancer in Chinese population. METHODS Polymorphism of CYP2E1 RsaI/PstI and GSTM1 was detected in 99 patients with lung cancer and 66 patients with benign pulmonary disease by PCR-RFLP and PCR. The association between genetic polymorphism and susceptibility of lung cancer was analyzed. RESULTS No significant difference in three RsaI/PstI genotype distribution of CYP2E1 was found between lung cancer group and control group (Chi-Square=1.374, P=0.241). (2) The frequency of GSTM1-null genotype in lung cancer group was significantly higher than that in control group (57.6% vs 40.9%, Chi-Square=4.401, P=0.036). (3) The individuals who carried with GSTM1-null genotype had a 1.96 fold increased risk of lung cancer (OR=1.96, 95%CI=1.042-3.689, P=0.037) than those who carried with GSTM1-present genotype. (4) When data were stratified by smoking status, the smokers who carried with c1/c1 genotype had a significantly higher risk of lung cancer (OR=3.525, 95%CI=1.168- 10.638, P=0.025) than those never-smokers who carried with at least one c2 allel. (5) When combination of polymorphism of CYP2E1 RsaI/PstI genotype and GSTM1 genotype was analyzed, compared with individuals who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was increased significantly (OR=3.449, 95%CI=1.001- 11.886, P=0.050). Considering smoking status, compared with never-smokers who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was remarkably increased (OR=11.553, 95%CI=1.068-124.944, P=0.044), as well as that for combination of GSTM1 null and at least one c2 allel genotype (OR=13.374, 95%CI=1.258-142.166, P= 0.032). CONCLUSIONS (1)GSTM1 null genotype is an important factor associated with increased risk of lung cancer. (2) The combination of c1/c1 and GSTM1-null genotype can remarkably increase risk of lung cancer both in smokers and non-smokers.

A randomized clinical trial of preoperative neoadjuvant chemotherapy followed by surgery in the treatment of stage III non-small cell lung cancer

BACKGROUND To explore the feasibility and toxicity of preoperative neoadjuvant chemotherapy followed by surgery in the treatment of stage III NSCLC and to evaluate its effects on tumor response, resection rate, tumor downstaging, and survival rate. METHODS From Jan. 1990 to Jan. 2001, 624 patients were randomly devided into group A ( preoperative neoadjuvant chemotherapy group) and group B ( control group, without neoadjuvant chemotherapy) . Group A had 314 patients and group B had 310 cases. The patients in group A were give 2 cycles of neoadjuvant chemotherapy, and operations were performed in 4 weeks after finishing the last chemotherapy. Twenty-one patients were given bronchial artery intervensional chemotherapy. The other 293 cases were given intravenous chemotherapy. The regimens included MVP in 68 cases, CAP in 36 cases, EP in 67 cases, VIP in 20 cases, Gem+ DDP in 30 cases, NVB+ DDP in 32 cases, Taxol+ NVB in 30 cases, and Taxol+ DDP in 10 cases. The patients in group B were firstly operated. Thoracic radiation therapy of 50-55 Gy was g iven in the patients with N1 and N2 disease both in group A and group B. RESULTS The tumor response to induction chemotherapy was 73. 57%( 231/ 314) in group A. The tumor downstaging was 43. 63%( 137/ 314) . The histological complete response was 15. 92%( 50/ 314) . The resection rate was 97. 69% in group A, and 91. 94% in group B. No significant differences of blood loss, operative complications and mortality were observed between the group A and group B. The 1-, 3-, 5- and 10-year survival rates were 89. 35%, 67. 46% , 34. 39% and 29. 34% in group A, and 87. 53%, 51. 54%, 24. 19% and 21. 64% in group B respectively. The long-term survival rate in group A was remarkably higher than that in group B ( P < 0. 01) . CONCLUSIONS The results demonstrate that the preoperative neoadjuvant chemotherapy is safe and effective. It is helpful to decrease the tumor staging , to increase the resection rate of the tumor, and to improve the long-term survival rate and life qualities of patients with stage III NSCLC.

Neoadjuvant therapy and risk of bronchopleural fistula after lung cancer surgery: a systematic meta-analysis of 14 912 patients

OBJECTIVE Neoadjuvant therapy has been extensively analyzed in studies addressing the risk factors of bronchopleural fistula, but their results vary hugely. Therefore, we conducted this meta-analysis to determine the association between neoadjuvant therapy and risk of bronchopleural fistula in patients undergoing lung cancer surgery. METHODS We searched PubMed and EMBASE to identify the full-text literatures that met our eligibility criteria. Odds ratio with 95% confidence interval served as the summarized statistics. Heterogeneity within this meta-analysis was evaluated by Q-test and I (2) statistic. Sensitivity analysis was performed for further assessments of robustness. Publication bias was detected by Beggs test and Eggers test. RESULTS Thirty studies enrolling 14 912 lung cancer cases were included into this meta-analysis. The incidence of bronchopleural fistula was 2.4% (354/14 912) in the large scale. Overall, neoadjuvant therapy significantly increased the risk of bronchopleural fistula after pulmonary resections (odds ratio: 2.166; 95% confidence interval: 1.398-3.357; P = 0.001). In subgroup analysis, neoadjuvant radiotherapy (odds ratio: 3.914; 95% confidence interval: 1.401-10.935; P = 0.009) and chemo-radiation (odds ratio: 2.533; 95% confidence interval: 1.353-4.741; P = 0.004) were significantly associated with the bronchopleural fistula risk but neoadjuvant chemotherapy was not (odds ratio: 1.857; 95% confidence interval: 0.881-3.911; P = 0.104). The impact of neoadjuvant therapy on bronchopleural fistula occurrence remains statistically prominent in the other subgroups. CONCLUSIONS Neoadjuvant therapy is significantly associated with the occurrence of bronchopleural fistula after lung cancer surgery. Both neoadjuvant radiotherapy and chemo-radiation significantly increase the bronchopleural fistula risk but neoadjuvant chemotherapy does not. Some limitations still exist in this meta-analysis. The updated high-quality studies can help to further confirm and enrich our discoveries in the future.

Prognostic factors for resection of isolated pulmonary metastases in breast cancer patients: a systematic review and meta-analysis

BACKGROUND Lung is a common organ of metastases in patients with primary breast cancer. Pulmonary metastasis of primary breast cancer is usually considered as a systemic disease, however, the systemic approaches have achieved little progress in terms of prolonging survival time. In contrast, some studies revealed a probable survival benefit of pulmonary metastasectomy for such patients. However, the prognostic factor for pulmonary metastasectomy in breast cancer patients is still a controversial issue. The aim of this study was to conduct a systematic review and meta-analysis of cohort studies to assess the pooled 5-year overall survival (OS) rate and the prognostic factors for pulmonary metastasectomy from breast cancer. METHODS An electronic search in MEDLINE (via PubMed), EMBASE (via OVID), CENTRAL (via Cochrane Library), and Chinese BioMedical Literature Database (CBM) complemented by manual searches in article references were conducted to identify eligible studies. All cohort studies in which survival and/or prognostic factors for pulmonary metastasectomy from breast cancer were reported were included in the analysis. We calculated the pooled 5-year survival rates, identified the prognostic factors for OS and combined the hazard ratios (HRs) of the identified prognostic factors. RESULTS Sixteen studies with a total of 1937 patients were included in this meta-analysis. The pooled 5-year survival rates after pulmonary metastasectomy was 46% [95% confidence interval (95% CI): 43-49%]. The poor prognostic factors were disease-free interval (DFI) (<3 years) with HR =1.70 (95% CI: 1.37-2.10), resection of metastases (incomplete) with HR =2.06 (95% CI: 1.63-2.62), No. of pulmonary metastases (>1) with HR =1.31 (95% CI: 1.13-1.50) and the hormone receptor status of metastases (negative) with HR =2.30 (95% CI: 1.43-3.70). CONCLUSIONS Surgery with a relatively high 5-year OS rate after pulmonary metastasectomy (46%), may be a promising treatment for pulmonary metastases in the breast cancer patients with a good performance status and limited disease. The main poor prognostic factors were DFI (<3 years), resection of metastases (incomplete), No. of pulmonary metastasis (>1) and hormone receptor status of metastases (negative). And prospective randomized trials will be needed to address these issues in the future.

Systematic short-term pulmonary rehabilitation before lung cancer lobectomy: a randomized trial

OBJECTIVES The goal of this study was to assess the impact of a preoperative 1-week, systematic, high-intensity inpatient exercise regimen on patients with lung cancer who had risk factors for postoperative pulmonary complications (PPCs). METHODS We conducted a randomized controlled trial with 101 subjects of a preoperative, 7-day systematic, integrated, high-intensity pulmonary exercise regimen. The control group received standard preoperative care. We analysed the occurrence of PPCs in both groups as the primary outcome; other outcomes included changes in blood gas, quality of life, peak expiratory flow rate, the 6-min walk distance and others. RESULTS The 6-min walk distance showed an increase of 22.9 ± 25.9 m in the intervention group compared with 4.2 ± 9.2 m in the control group, giving a between-group difference of 18.7 m (95% confidence interval: 8.8-28.6; P < 0.001); the peak expiratory flow increased by 25.2 ± 24.6 l/min, compared with 4.2 ± 7.7 l/min (between-group difference: 21.0 m, 95% confidence interval: 7.2-34.8; P = 0.003). The intervention group had a shorter average total (15.6 ± 3.6 vs 17.7 ± 5.3 days, P = 0.023) and postoperative length of stay (6.1 ± 3.0 vs 8.7 ± 4.6 days, P = 0.001) than the control group; the incidence of PPCs (9.8%, 5/51 vs 28.0%, 14/50, P = 0.019) was significantly lower. A multivariable analysis of the risk of PPCs identified short-term rehabilitation intervention to be an independent risk factor (odds ratio = 0.156, 95% confidence interval: 0.037-0.649, P = 0.011). CONCLUSIONS The study results suggested that a systematic, high-intensity pulmonary exercise programme was a practical strategy when performed preoperatively in patients with lung cancer with risk factors for PPCs. CLINICAL TRIAL REGISTRATION ChiCTR-IOR-16008109.