First-line chemotherapy or in combination with programmed cell death protein-1 antibody in patients with metastatic or recurrent biliary tract cancer.

BACKGROUND: Although immune checkpoint blockade therapy has achieved great success in various types of cancers, studies on biliary tract cancer are limited. This study aimed to assess the efficacy and tolerability of immune checkpoint inhibitors (ICIs) combined with chemotherapy in Chinese patients with BTC. METHODS: We collected medical records of 130 pathologically diagnosed metastatic or recurrent BTC patients who had not received chemotherapy in the advanced stage. Eligible patients who received first-line chemotherapy ± ICIs were enrolled in the efficacy and safety analysis. We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and duration of response (DoR) between the ICI plus chemotherapy group and chemotherapy alone group. RESULTS: Of 90 enrolled patients, 45 received ICIs plus chemotherapy and 45 received chemotherapy. The median follow-up times were 18.7 and 19.6 months, respectively. The median PFS was 5.9 months (95% CI: 4.3-7.5) with ICIs plus chemotherapy, which was significantly longer than the 4.2 months (95% CI: 2.1-6.5) with chemotherapy (hazard ratio [HR] 0.62, 95% CI: 0.39-0.94; P = 0.0306). The median OS was 14.7 months (95% CI: 11.4-18.0) compared with 14.2 months (95% CI: 12.5-15.9) (HR 0.93; 95% CI: 0.57-1.50; P = 0.765). Grade 3 or 4 treatment-related adverse events were similar between these two groups (71.1% and 64.4%, respectively). CONCLUSION: Although first-line ICI therapy plus chemotherapy showed a significant improvement in the median PFS compared with chemotherapy in metastatic or recurrent BTC, the benefit did not translate into a statistically significant OS prolongation. The safety profile for ICIs plus chemotherapy was similar to chemotherapy alone.

The relationship between chronic obstructive pulmonary disease and non-small cell lung cancer in the elderly.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and NSCLC often coexist and have poor prognoses, but studies investigating the impact of COPD on NSCLC have reported inconsistent findings. The objective of this study was to compare survival between NSCLC patients with and without COPD. METHODS: Medical records were retrospectively collected from 301 elderly patients pathologically diagnosed with NSCLC from the Chinese PLA General Hospital. Ultimately, a total of 200 patients were enrolled in the analysis. The survival rates between the COPD-NSCLC and non-COPD NSCLC were assessed using log-rank and Cox proportional hazard regression analyses. RESULTS: A total of 117 COPD-NSCLC and 93 non-COPD NSCLC patients were enrolled in the analysis. The median overall survival times were 108.5 months in the non-COPD group and 45.0 months in the COPD group (HR: 2.05; 95% CI, 1.36-2.97, P = 0.0004). After 118 patients underwent propensity score matching, the median overall survival times were 100.6 months in the non-COPD group and 51.9 months in the COPD group (HR: 1.59; 95% CI, 1.096-2.64, P = 0.0459). The multivariate analysis showed that presence of COPD (HR 1.619, P = 0.030), old age (HR 1.007, P < 00001), an advanced disease stage (stage Ⅲ HR 5.513, P < 0.0001; stage Ⅳ HR 11.743, P < 0.0001), the squamous cell carcinoma histological subtype (HR 3.106, P < 0.0001), the presence of a cough (HR 2.463, P = 0.001) a higher serum carcinoembryonic antigen level (HR 1.001, P = 0.023) and higher NRL (HR 2.615, P = 0.007) were independent factors that were significantly associated with poorer survival. CONCLUSION: A diagnosis of COPD had significant poorer survival outcomes in NSCLC than that of patients without COPD in this elderly population.

[Clinical characteristics and risk factors affecting outcomes of elderly patients with non-small cell lung cancer complicated by chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the clinical features, treatment strategy and risk factors affecting the prognosis of elderly patients with non-small cell lung cancer (NSCLC) complicated by chronic obstructive pulmonary disease (COPD). METHODS: We retrospectively analyzed the data of elderly patietns (>60 years) with newly diagnosed NSCLC complicated by COPD at the Geriatric Institution of General Hospital of PLA between January, 2000 and June, 2015. The clinical data collected included history of smoking, pulmonary function test results, initial treatments, TNM stage, chief complaints, comorbidities and laboratory tests. The Cox proportional hazards regression model was used to explore the prognostic factors in these patients. RESULTS: A total of 200 NSCLC patients were reviewed, of which 107 (53.5%) patients had the co-morbidity of COPD as confirmed by spirometry using bronchodilator test. The median survival of the patients with NSCLC complicated by COPD was 45.8 months with 1-, 3-, 5-, and 10-year survival rates of 80.4%, 55.4%, 41.0% and 20.0%, respectively. Stratification analysis showed that patients with COPD Gold grades 1 and 2 had a significant longer median overall survival (51.7 and 43.1 months, respectively) than those with grade 3/4 (16.9 months; P=0.020 and 0.043, respectively). Univariate and multivariate analyses using Cox proportional hazards regression model showed that an older age, a higher Gold grade, advanced disease stage (stages III and IV), squamous cell carcinoma, nonsurgical initial treatment, coughing and an elevated serum CEA level were independent risk factors for shorter survival of the patients. CONCLUSION: Multiple prognostic factors can affect the outcomes of elderly patients with NSCLC complicated by COPD, and a higher COPD Gold grade that fails to respond to treatment within 3 months is the independent risk factor for survival of the patients.

A propensity-matched analysis of surgery and stereotactic body radiotherapy for early stage non-small cell lung cancer in the elderly.

Elderly patients with early stage non-small cell lung cancer (NSCLC) who undergo surgical resection are at a high risk of treatment-related complications. Stereotactic body radiation therapy (SBRT) is considered an alternative treatment option with a favorable safety profile. Given that prospective comparative data on SBRT and surgical treatments are limited, we compared the 2 treatments for early stage NSCLC in the elderly.We retrospectively collected information from the database at our geriatric institution on patients with clinical stage IA/B NSCLC who were treated with surgery or SBRT. The patients were matched using a propensity score based on gender, age, T stage, tumor location, pulmonary function (forced expiratory volume in 1 second [FEV1]% and FEV1), Charlson comorbidity score, and World Health Organization performance score. We compared locoregional control rate, recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) between the 2 treatment cohorts before and after propensity score matching.A total of 106 patients underwent surgery, and 74 received SBRT. Surgical patients were significantly younger (72.6 ±â€Š7.9 vs 82.6 ±â€Š4.1 years, P = 0.000), with a significantly higher rate of adenocarcinoma (P = 0.000), better Eastern Cooperative Oncology Group performance scores (P = 0.039), and better pulmonary function test results (P = 0.034 for predicted FEV1 and P = 0.032 for FEV1). In an unmatched comparison, there were significant differences in locoregional control (P = 0.0012) and RFS (P < 0.001). The 5-year OS was 69% in patients who underwent surgery and 44.6% in patients who underwent SBRT (P = 0.0007). The 5-year CSS was 73.9% in the surgery group and 57.5% in the SBRT group (P = 0.0029). Thirty-five inoperable or marginally operable surgical patients and 35 patients who underwent SBRT were matched to their outcomes in a blinded manner (1:1 ratio, caliper distance = 0.25). In this matched comparison, the follow-up period of this subgroup ranged from 4.2 to 138.1 months, with a median of 58.7 months. Surgery was associated with significantly better locoregional control (P = 0.0191) and RFS (P = 0.0178), whereas no significant differences were found in OS (5-year OS, 67.8% for surgery vs 47.4% for SBRT, P = 0.07) or CSS (67.8% for surgery vs 58.2% for SBRT, P = 0.1816).This retrospective analysis found superior locoregional control rates and RFS after surgery compared with SBRT, but there were no differences in OS or CSS. SBRT is an alternative treatment option to surgery in elderly NSCLC patients who cannot tolerate surgical resection because of medical comorbidities. Our findings support the need to compare the 2 treatments in randomized controlled trials.

MiR-34b/c rs4938723 Polymorphism Significantly Decreases the Risk of Digestive Tract Cancer: Meta-analysis.

BACKGROUND: Previous studies investigating the association between miR-34b/c rs4938723 polymorphism and cancer risk showed inconclusive. Here, we performed meta-analysis to investigate the association between miR- 34b/c rs4938723 polymorphism and digestive cancer risk. MATERIALS AND METHODS: Literature database including PubMed, OVID, Chinese National Knowledge Infrastructure (CNKI) were searched for publications concerning the association between the miR-34b/c rs4938723 polymorphism and digestive cancer risk. RESULTS: A total of 6 studies consisting of 3246 cases and 3568 controls were included in this meta-analysis. The combined analysis suggested the miR-34b/c rs4938723 polymorphism significantly reduced digestive cancer risk under allelic model, homogeneous co-dominant model and recessive model (C vs T: OR=0.88, 95%CI=0.82-0.95, p-value=0.001; CC vs TT: OR =0.67, 95%CI=0.57-0.80, p-value=0.000; CC vs TT/TC: OR=0.68, 95%CI=0.58-0.80, p-value=0.000). Q-test and I2 test revealed no significant heterogeneity in all genotype comparisons. The Begger's funnel plot and Egger's test did not show significant publication bias. CONCLUSIONS: The current evidence supports the conclusion that the miR-34b/c rs4938723 polymorphism decreases an individual's susceptibility to digestive cancers.

Mutations in the mitochondrial ATPase6 gene are frequent in human osteosarcoma.

To explore the polymorphisms and mutations of mitochondrial ATPase6 gene in Chinese patients with osteosarcoma and their possible association with carcinogenesis, direct DNA sequencing method was used to detect the variants of the mitochondrial ATPase6 gene in 39 patients with osteosarcoma. We found mutations of the mitochondrial ATPase6 gene in 24/39 (61.5%) of the tested osteosarcoma samples, and identified 27 variant sites in ATPase6 coding regions. We did not detect any new polymorphisms in osteosarcoma, nor was there any association between variants and the three histopathological subtypes. These data demonstrated that mtDNA mutations within the ATPase6 gene are a frequent event in Chinese patients with osteosarcoma.

Heme oxygenase-1 system, inflammation and ventilator-induced lung injury.

Mechanical ventilation is an indispensable supportive intervention for acute respiratory failure. However, mechanical ventilation can provoke ventilator-induced lung injury, which remains one of the major causes of morbidity and mortality in critically ill patients. Excessive inflammatory response characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators contributes to the pathogenesis of ventilator-induced lung injury. At present, apart from the protective ventilation strategy, no other pharmacological intervention is available to attenuate ventilator-induced lung injury. Heme oxygenase-1 (HO-1) is the inducible isoform of the first and rate-limiting enzyme which degrades heme into carbon monoxide, ferritin and bilirubin. Accumulating evidence suggests that HO-1 system may function as a crucial negative regulator in the modulation of inflammatory process. This anti-inflammatory action of HO-1 is mediated essentially by the regulation of the key cells involved in inflammation and restoration of the balance between pro-inflammatory and anti-inflammatory mediators. Therefore, HO-1 system represents a promising therapeutic target for intervention of ventilator-induced lung injury.

Mutations in the mitochondrial DNA D-Loop region occur frequently in human osteosarcoma.

To explore the polymorphisms and mutations of mitochondrial D-Loop region in osteosarcoma and their possible association with carcinogenesis, direct DNA sequencing method was used to detect the variants of the mitochondrial D-Loop in 20 patients with osteosarcoma. We found mutations of the mitochondrial D-Loop in 14/20 (70%) of the tested osteosarcoma samples, including 34 novel mutations. We did not detect any new polymorphisms in osteosarcomas, nor was there any association between variants and the three histopathological subtypes. We identified 89 variant sites, most of which were within the hypervariable I and II (HV I and HV II) regions. These data suggest that mtDNA mutations within the D-Loop region, particularly the HV I and HV II segments, are a frequent event in osteosarcomas.