Yuan Zeng

Correlation between epidermal growth factor receptor mutations and nuclear expression of female hormone receptors in non-small cell lung cancer: a meta-analysis

BACKGROUND Compared with male, female non-small cell lung cancer (NSCLC) patients have better response when treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), suggesting a potential association between female hormones and EGFR mutation. However, the results provided by previous studies were inconclusive and controversial. We sought to examine the link between the expression of nuclear female hormone receptors and EGFR mutations in NSCLC. METHODS Electronic databases were used to search the relevant articles. The involved hormone receptors included estrogen receptor (ER) and progesterone receptor (PR). The primary endpoint was the occurrence of ER/PR expression and EGFR mutation in NSCLC patients. RESULTS Five studies fulfilled the criteria and were included in our analysis. Patients with high ER-β expression had higher positive EGFR mutation than low ER-β patients (44.2% vs. 23.7%), and there was a significant difference between the two groups [odds radio (OR) 3.44, 95% confidence interval (CI): 2.40-4.93, Z=6.72, P<0.001]. However, there is no significant correlation between EGFR mutations and ER-α (when included ER-α3, OR 1.20, 95% CI: 0.62-2.33, Z=0.55, P=0.58; and when included ER-α4, OR 1.18, 95% CI: 0.62-2.25, Z=0.51, P=0.61) or PR (OR 1.29, 95% CI: 0.40-4.10, Z=0.43, P=0.67). No significant publication bias was observed. CONCLUSIONS High nuclear expression of ER-β, but not ER-α or PR is correlated with EGFR mutations in NSCLC. The underlying mechanism and potential translational relevance warrant further investigation.

XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer.

X-ray radiation resistance associated 1 (XRRA1) has been found to regulate the response of human tumor and normal cells to X-radiation (XR). Although XRRA1 overexpression is known to be involved in cancer cell response to XR, there are no reports about whether the expression of XRRA1 in tumors can adjust radioresistance. It is widely known that cell cycle arrest could cause radioresistance. We found that blocked XRRA1 expression could lead to cell cycle G2/M arrest by the regulation of cyclin A, cyclin E, and p21 proteins in colorectal cancer (CRC) and expression of XRRA1 reduced cell cycle arrest and increased cell proliferation in CRC. However, whether regulation of the cell cycle by XRRA1 can influence radioresistance is poorly characterized. Correspondingly, DNA repair can effectively lead to radioresistance. In our study, when cancer cells were exposed to drugs and ionizing radiation, low expression of XRRA1 could increase the phosphorylation of DNA repair pathway factors CHK1, CHK2, and ATM and reduce the expression of γ-H2AX, which is believed to participate in DNA repair in the nucleus. Crucially, our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway.

Adoptive Immunotherapy in Postoperative Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background Adoptive immunotherapy (AI) has been applied in the treatment of non-small-cell lung cancer (NSCLC) patients, but the value of postoperative AI has been inconclusive largely as a result of the small number of patients included in each study. We performed a systematic review and meta-analysis to address this issue for patients with postoperative NSCLC. Methods Pubmed, Embase, Cochrane Library were searched for randomized controlled trials comparing adoptive immunotherapy with control therapies in postoperative NSCLC patients. The primary endpoint was overall survival. Hazard ratio (HR) was estimated and 95% confidence intervals (CI) were calculated using a fixed-effect model. Results Compared with control therapies, analyses of 4 randomized controlled trials (472 patients) showed a significant benefit of adoptive immunotherapy on survival (hazard ratio [HR] 0.61, 95% CI 0.45–0.84, p = 0.002), and a 39% reduction in the relative risk of death (no evidence of a difference between trials; p = 0.16, I² = 42%). In subgroup analyses by treatment cycles and treatment regimen, significant OS benefit was found in combination therapy of AI with chemotherapy, regardless of whether or not the treatment cycles were more than 10 cycles. Conclusion Adoptive immunotherapy has the potential to improve overall survival in postoperative NSCLC. The findings suggest this is a valid treatment option for these patients. Further randomized clinical trials are urgently needed.

Three-Dimensional Versus Two-Dimensional Video-Assisted Endoscopic Surgery: A Meta-analysis of Clinical Data

BackgroundThere have been no studies to systematically evaluate the two display (3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in clinical settings; thus, we conducted one to evaluate the safety and efficacy of different visualization systems (two-dimensional and three-dimensional) during endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings.MethodsA comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy, prospective vs. retrospective study, malignant vs. benign diseases) were examined. Meta-regression was conducted to explore the source of heterogeneity.ResultsTwenty-three articles were considered in this analysis, of which 7 were thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D display. Overall, significantly shorter operating time (SMD −0.69; p = <0.001), less blood loss (SMD −0.26; p = 0.028) and shorter hospital stays (SMD −0.16; p = 0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity (OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage duration (SMD −0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were similar between the two groups. Comparison of the overall outcomes in each subset showed consistency in all groups.ConclusionsThis up-to-date meta-analysis reveals that the 3D display system is superior to the 2D system in clinical settings with significantly shorter operating time, less blood loss and shorter hospital stay. These findings suggest that, in laparoscopic or thoracoscopic surgeries, 3D endoscopic system is preferable when condition permits. Future efforts should be made on decreasing the side effects of 3D display and increasing its cost-effectiveness.

Direct comparison of autofluorescence bronchoscopy (AFB) and the combination of autofluorescence bronchoscopy and white light bronchoscopy (AFB + WLB) for detecting airway cancerous and precancerous lesions: a systematic review and meta-analysis

Background: Autofluorescence bronchoscopy (AFB) presents high sensitivity but low specificity for detecting cancerous and precancerous lesions; its specificity and overall diagnostic performance may be improved when combining with white light bronchoscopy (AFB + WLB). Methods: We conducted a systematic review and meta-analysis through searching PubMed and Web of Science from the inception date of each database to 31 Dec 2017. Eligible comparative studies should contain sufficient data of AFB versus AFB + WLB to construct 2×2 tables. In addition, the samples detected by bronchoscopies should be confirmed by histopathology. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC) were estimated by a random-effect model. Results: We included seven comparative studies involving a total of 904 patients and 2,740 biopsy specimens. According to the original reported data, no specificities of AFB + WLB were higher than the specificities of AFB. In our meta-analysis, the sensitivity, specificity, DOR and AUC of AFB were 88% (95% CI: 65–97%), 63% (49–75%), 12 [3–54] and 77% (73–81%), respectively; those of AFB + WLB were 90% (77–96%), 54% (39–68%), 11 [4–34] and 78% (74–81%), respectively. Conclusions: Both AFB and AFB + WLB presented similar diagnostic performance for cancerous and precancerous lesions. In other word, AFB + WLB did not present superiority compared to AFB alone, especially in terms of the specificity.

Esophageal cancer in patients under 50: a SEER analysis

Background Concomitant with rising rates of esophageal adenocarcinoma, there has been a significant increase of diagnoses among relatively younger individuals. However, most studies that focus on esophageal cancer (EC) in younger patients have had small sample sizes of patients treated at a single institute. The aim of this study was to analyze the clinical characteristics, outcomes and independent prognostic factors for EC in patients under 50-year-old using a large, multi-center dataset. Methods The national Surveillance, Epidemiology, and End Results (SEER) database was analyzed for EC reported from 2004 to 2013. Patients were divided into two groups, those under 50-year-old and those 50 years or older, and comparisons were made regarding demographics, histology, stage distribution, treatment, overall survival (OS), and esophageal cancer-specific survival (ECSS). Multivariate Cox proportional hazard regression analyses were also used to identify independent prognostic factors. Results Among the 16,544 eligible patients, 1,385 (8.37%) were under 50 and 15,159 (91.63%) were over 50. Compared with the older group, patients under 50 were characterized by a higher frequency of males, lower esophagus involvement, adenocarcinoma histology, stage III/IV disease, and receiving esophagectomy or radiation therapy. The stage-wise OS and ECSS were significantly better in the younger group (P<0.001). The multivariate analysis indicated that African-American heritage, grade III or IV, later stage, and not undergoing surgical or radiation therapy were independent negative prognostic factors of ECSS for patients under 50. Conclusions EC patients under 50-year-old had distinctive clinicopathological characteristics compared with patients over 50-year-old. Despite more often presenting with stage III and IV disease, survival rates were better in the younger cohort. Prognostic factors for ECSS in patients under 50 differed from those in all age patients.

Esophageal cancer in elderly patients: a population-based study

Background As the aging issue and increased elderly esophageal cancer (EC) patients, we sought to study the clinical characteristics, treatment modality and outcomes of EC patients 70 years or older compared with those younger than 70 years old. Methods The national surveillance, epidemiology, and end results (SEER) database for the period from 1973 to 2013 was analyzed. The patient and treatment characteristics were compared between the age groups. Multivariate Cox proportional hazard regression analyses were also performed to identify independent prognostic factors. Propensity-score matching analyses (PSA) regarding survival after different treatments were also performed in locoregional EC. Results Compared with the younger group, patients 70 years or older were characterized by having a higher proportion of patients with female gender, white race, localized disease, non-adenocarcinoma and without any treatment, as well as inferior overall survival (OS) [hazard ratio (HR), 1.324] and EC-specific survival (HR, 1.270). In addition, older patients shared same independent prognostic factors with younger patients, including age, histology and race. Specifically, compared with those receiving no intensive treatments, surgery alone (HR, 0.342), both surgery and RT (HR, 0.323) and RT only (HR, 0.525) were favorable among elderly patients, as confirmed by both multivariate adjustment and PSA. Conclusions Compared to younger EC patients, those 70 years or older showed distinctive clinical characteristics and inferior survival. Despite showing a higher proportion of localized disease, patients 70 years or older were less likely to be subjected to surgery or/and RT. Thus, the role of intensive treatments, which were identified as favorable factors among elderly patients in this study, warrants further investigation.

The impact of spontaneous ventilation on non-operative lung injury in thoracic surgery: a randomized controlled rabbit model study

OBJECTIVES One-lung ventilation (OLV) with general anaesthesia may increase adverse effects after thoracic surgery, specifically ventilator-induced lung injury. Spontaneous ventilation (SV) has no mechanical ventilation process, thus, we established a rabbit model to assess non-operative lung injury between OLV and SV. METHODS Thirty-six rabbits were randomly divided into 6 groups: OLV and SV (0, 2 and 4 h). Blood gas analysis was performed after thoracic surgery. Lung tissue and bronchoalveolar lavage fluid were obtained from the non-operative lung. Pathological injury score in lung tissue and tumour necrosis factor α (TNF-α) level in bronchoalveolar lavage fluid using enzyme-linked immunosorbent assay were determined. Moreover, messenger RNA and protein of TNF-α in lung tissue were also determined by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS Compared with the OLV group, significantly higher partial pressure of carbon dioxide (47.78 ± 3.57 vs 38.95 ± 3.88 mmHg, P < 0.01) and partial pressure of oxygen (101.08 ± 13.1 vs 85.6 ± 11.07 mmHg, P < 0.01), as well as a significantly lower pathological injury score (6.83 ± 1.17 vs 8.83 ± 1.72, P < 0.05), TNF-α level in bronchoalveolar lavage fluid (290.32 ± 29.38 vs 368.43 ± 31.26 pg/ml, P < 0.01), TNF-α messenger RNA (6.31 ± 1.13 vs 8.6 ± 1.34, P < 0.01), immunostaining intensity in lung tissue were found at 4 h in the SV group. However, there are no significant differences between OLV and SV groups at 2 h (P > 0.05), except in TNF-α messenger RNA. CONCLUSIONS Based on this rabbit model, SV for thoracic surgery is not inferior to OLV in terms of lung injury. Considering our results, when performing time-consuming thoracic procedures under OLV, surgeons should more closely examine patients for non-operative lung injury postoperatively.

Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

BACKGROUND Breast cancer susceptibility gene 1 (BRCA1) expression has been suggested as a predictor in anti-neoplastic treatment with anti-microtubule agents. However, the existing evidence is conflicting. Consulting the literature, we sought to examine the true impact of BRCA1 expression on the efficacy of anti-microtubule agents. METHODS Medline by PubMed and Embase databases were searched for eligible studies. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Additional subgroup analyses stratified for detection methods, regimen, and patient origin were also performed. RESULTS A total of 13 relevant studies involving a total of 1,490 cases were enrolled. Involved agents included paclitaxel, docetaxel and vinorelbine; Malignancies included non-small cell lung cancer, gastric cancer, esophageal carcinoma, ovarian carcinoma, malignant pleural mesothelioma, breast cancer, and small cell lung cancer. Through meta-analyses, we observed a potentially greater ORR in the population with high BRCA1 expression vs. low BRCA1 expression (OR 1.63, 95% CI: 0.92 to 2.88, P=0.09) but the heterogeneity is severe (P=0.01; I(2)=61%). Similar results were observed in PFS (high vs. low expression, HR 0.93, 95% CI: 0.75 to 1.15, P=0.49; heterogeneity, P<0.01, I(2)=75%). After stratification by testing methods, a significantly higher ORR in the population with high BRCA1 expression was shown in the subgroup using mRNA as a quantitative method (OR 2.90, 95% CI: 1.92 to 4.39, P<0.01; I(2)=0) whereas the difference in the subgroup using immunohistochemistry (IHC) was not significant (OR 0.60, 95% CI: 0.33 to 1.10, P=0.10; I(2)=0). Stratification by regimen (platinum-based vs. non platinum-based) and patient origin (Asian vs. Caucasian) did not reduce the heterogeneity. CONCLUSIONS Although the predictive value of BRCA1 expression on the anti-microtubule chemotherapy remained uncertain based on overall results, our exploratory analyses suggested that detection using mRNA might be a preferred technique, however, further validation is required to substantiate our findings.