Prevention effect of low-temperature atomization inhalation for radiation induced oral mucositis in patients with head and neck cancer undergoing radiotherapy.

Purpose: To investigate the prevention effect of low-temperature atomization inhalation for radiation induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radiotherapy. Patients and methods: A total of 68 patients with HNC (including nasopharyngeal cancer) undergoing radiotherapy were divided into an intervention group (33 cases) and a control group (35 cases). During radiotherapy, the intervention group received low-temperature (between 4°C and 8°C) atomization inhalation; while the control group received normal temperature (between 18°C and 24°C) atomization inhalation. Atomization inhalation was performed twice a day, 20 minutes per time, using distilled water. The incidence and severity of OM was evaluated every week during radiotherapy. The comparation was made between the two groups. Results: The two groups were comparable among age, sex, Eastern Cooperative Oncology group (ECOG) score, body mass index (BMI) before radiotherapy, BMI loss during radiotherapy, original tumor site, pathological type, TNM stage, and mean oral cavity irradiated dose. There was a significant difference in the incidence of OM between the two groups (P<0.05). There were fewer patients with severe OM in the intervention group compared to the control group (P<0.05). The onset time of OM in the intervention group was delayed by about 4 days compared to that in the control group (P<0.05). Low-temperature atomization inhalation helped to avoid radiotherapy interruption in the intervention group. No patient in the intervention group suffered any adverse reaction for low-temperature atomization inhalation treatment. Conclusions: Low-temperature atomization inhalation can reduce the incidence and severity of OM, and slow down the progression process of it. It can be used as a new prevention method during radiotherapy, and should be promoted in clinical practice.

Effect of bone marrow mesenchymal stem cells on the polarization of macrophages.

Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is excessive, systemic inflammatory response syndrome may develop. Sepsis is the most common complication of severe burns and is a systemic inflammatory response syndrome that is caused by infectious factors and is capable of leading to multiple organ dysfunction and potentially death. Research concerning the mechanism and treatment of sepsis is crucial. Macrophages are an important type of immune cell that remove invasive pathogens and are involved in innate and adaptive immune responses. It has been previously reported that bone marrow mesenchymal stem cells (BMSCs) affect macrophages by regulating immunity. The present study aimed to investigate the effect of BMSCs on macrophage polarization in vivo and in vitro, in addition to the potential therapeutic effect of these cells on experimental sepsis. BMSCs and peritoneal macrophages were isolated from Sprague­Dawley rats and co­cultured overnight as a mixed culture or Transwell system, and subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the medium was replaced with normal complete medium for various durations and supernatants were collected to extract proteins and cells for ELISA, western blot and flow cytometry analysis to investigate different aspects of macrophages. Sepsis was induced in Sprague­Dawley rats by injection of LPS (5 mg/kg), followed by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung tissues were harvested for pathological observation and peritoneal macrophages were collected for flow cytometry analysis to assess the expression of markers, including cluster of differentiation (CD)68 (used for gating), CD11c and CD206. The results demonstrated that, in the culture medium, LPS stimulation increased the expression of CD11c in macrophages, and the levels of tumor necrosis factor­α and inducible nitric oxide synthase were also increased. By contrast, in macrophages treated with BMSCs directly, the expression of CD11c was reduced compared with the LPS­stimulated macrophage alone group. However, the secretion of interleukin­10, transforming growth factor­ß and arginase­1 was increased in the direct co­culture group, compared with the LPS­stimulated macrophage alone group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage expression of CD11c in the rat model of sepsis. The results of the present study demonstrated that BMSCs co­cultured with macrophages directly inhibited macrophage differentiation into the M1 phenotype and reduced inflammation in macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c in peritoneal macrophages and reduced the pathological inflammatory response in the lungs. The findings of the present study demonstrated that BMSCs may reduce the extent of the systemic inflammatory response, which may contribute to the development for a novel type of treatment for sepsis in the future.

The effect of non-small cell lung cancer histology on survival as measured by the graded prognostic assessment in patients with brain metastases treated by hypofractionated stereotactic radiotherapy.

BACKGROUND: The purpose of this study was to investigate the impact of histology on survival stratified by the Graded Prognostic Assessment (GPA) for non-small cell lung cancer (NSCLC) in a group of selected patients treated recently. METHODS: A total of 171 NSCLC patients with brain metastases treated by hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy between 2001 and 2011 were included. The GPA score was calculated for each patient. Tumor histologies were categorized into adenocarcinoma (ADCA) and non-ADCA. Median survival time (MST, in months) was calculated using the Kaplan-Meier method. The log-rank test was used to determine statistical differences. RESULTS: MSTs by histology were: ADCA 15 (n = 92) and non-ADCA 10 (n = 79) (p < 0.001). For all patients, the MSTs by GPA score were: GPA 3.5-4, 24; GPA 2.5-3, 15; GPA 1.5-2, 9 and GPA 0-1, 6 (p < 0.001). The histology of ADCA showed a statistically significant higher MST than non-ADCA for patients with GPA 2.5-4. For GPA 2.5-3, MSTs were: ADCA 18, non-ADCA 10 (p = 0.007); for GPA 3.5-4, MSTs were: ADCA 30, non-ADCA 17 (p = 0.046). For GPA 0-2, MSTs did not differ significantly by histology. For GPA 0-1, MSTs were: ADCA 8, non-ADCA 4 (p = 0.146); GPA 1.5-2, MSTs were: ADCA 10, non-ADCA 8 (p = 0.291). We further found that non-ADCA in upper GPA class (3.5-4) had similar survival with ADCA in lower GPA class (2.5-3) (MSTs were 17 and 18, respectively, p = 0.775). This phenomenon also happened between patients of non-ADCA in upper GPA class (2.5-3) and those of ADCA in lower GPA class (1.5-2) (MSTs were both 10, p = 0.724). CONCLUSIONS: We confirmed that the histology of NSCLC had effect on the GPA in these selected patients treated recently. ADCA showed a statistically significant higher MST than non-ADCA with GPA 2.5-4. The non-ADCA in upper GPA classes (3.5-4 and 2.5-3) had similar survival to ADCA in lower GPA classes (2.5-3 and 1.5-2, respectively). The histology as a new factor should be added to the original GPA for NSCLC.

Hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy for patients with newly diagnosed brain metastases from non-small cell lung cancer.

OBJECT: This study was undertaken to analyze outcomes in patients with newly diagnosed brain metastases from non-small cell lung cancer (NSCLC) who were treated with hypofractionated stereotactic radiotherapy (HSRT) with or without whole-brain radiotherapy (WBRT). METHODS: One hundred seventy-one patients comprised the study population. Fifty-four patients received HSRT alone, and 117 patients received both HSRT and WBRT. The median survival time (MST) was determined using the Kaplan-Meier method. Recursive Partitioning Analysis (RPA) and Graded Prognostic Assessment (GPA) were also used to evaluate the results. Univariate and multivariate analyses were performed to determine significant prognostic factors for overall survival. Tumor control, radiation toxicity, and cause of death in the HSRT and HSRT+WBRT groups were evaluated. RESULTS: The MST for all patients was 13 months. According to the Kaplan-Meier method, the probability of survival at 1, 2, and 3 years was 51.2%, 21.7%, and 10.1%. The MSTs for RPA Classes I, II, and III were 19, 12, and 5 months, respectively; and the MSTs for GPA Scores 4, 3, 2, and 1 were 24, 14, 12, and 6 months, respectively. The MSTs in the HSRT+WBRT and HSRT groups were 13 and 9 months (p = 0.044), respectively, for all patients, 13 and 8 months (p = 0.031), respectively, for patients with multiple brain metastases, and 16 and 15 months (p = 0.261), respectively, for patients with a single brain metastasis. The multivariate analysis showed that HSRT+WBRT was a significant factor only for patients with multiple brain metastases (p = 0.010). The Kaplan-Meier-estimated tumor control rates at 3, 6, 9, and 12 months were 92.2%, 82.7%, 79.5%, and 68.3% in the HSRT+WBRT group and 73.5%, 58.4%, 51.0%, and 43.3% in the HSRT group, respectively, in all 165 patients (p = 0.001). The estimated tumor control rates at 3, 6, 9, and 12 months were 94.3%, 81.9%, 79.6%, and 76.7%, respectively, in the HSRT+WBRT group and 77.8%, 61.4%, 52.6%, and 48.2%, respectively, in the HSRT group in the 80 patients harboring a single metastasis (p = 0.009). The estimated tumor control rates at 3, 6, 9, and 12 months were 90.5%, 83.5%, 79.5%, and 60.9%, respectively, in the HSRT+WBRT group and 68.2%, 54.5%, 48.5%, and 36.4%, respectively, in the HSRT group in the 85 patients with multiple metastases (p = 0.010). The toxicity incidences of Grade 3 or worse were 6.0% (7 of 117 patients) in the HSRT+WBRT group and 1.9% (1 of 54 patients) in the HSRT group (p = 0.438). The differences in neurological death rates between the HSRT+WBRT group and the HSRT group were not statistically significant (34.4% vs 44.7%, p = 0.125, in all patients; 30.0% vs 52.0%, p = 0.114, in patients with a single metastasis; and 38.0% vs 36.4%, p = 0.397, in patients with multiple metastases). CONCLUSIONS: The overall survival results in the present study were similar to those in other studies. Hypofractionated stereotactic radiotherapy provides an alternative method to traditional stereotactic radiosurgery. We suggest that WBRT should be combined with HSRT in patients with single or multiple newly diagnosed brain metastases from NSCLC.