Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination.

In spontaneously hypertensive rats, we studied the participation of xanthine oxidase-linked free radical in ischemia and reperfusion-induced cerebral injury, using allopurinol, a xanthine oxidase inhibitor. The loss of righting reflex was noted in some animals after a 4 hour occlusion of bilateral common carotid arteries and 19 of 25 animals died within 72 hours after reperfusion. One hour after reperfusion, the cerebral water content increased significantly, with an increase in sodium content and a decrease in potassium content. In 7 animals treated with oral administrations of allopurinol (200 mg/kg) 24 hours and 1 hour before occlusion, no death was found either during occlusion or after reperfusion, and the loss of righting reflex was noted in only one animal 24-72 hours following reperfusion. The increase in cerebral water content and accompanied changes in electrolyte contents were clearly prevented by allopurinol. These results suggest the possibility that the production of xanthine oxidase-linked free radical participates in cerebral injury due to ischemia and reperfusion in spontaneously hypertensive rats.

We evaluated the failure pattern after definitive chemoradiotherapy in patients with stage III nonesmall-cell lung cancer harboring epidermal growth factor receptor mutations and/or anaplastic lymphoma kinase translocation. Although the epidermal growth factor receptor-mutant group showed a lower incidence of infield failure and higher incidence of out-of-field failure, the group with anaplastic lymphoma kinase translocation showed no characteristic in-field or out-of-field failure pattern. Introduction: This study was aimed at clarifying the failure pattern after definitive chemoradiotherapy in patients with stage III nonesmall-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) translocation. Methods and Materials: This retrospective study was a singleinstitution study conducted on patients with unresectable stage III non-squamous NSCLC treated by definitive chemoradiotherapy between January 2006 and March 2016. Only patients with information of EGFR mutations and/or ALK translocation were included. The prognosis and initial recurrence patterns were compared according to the presence/absence of EGFR mutation and/or ALK translocation. Results: A total of 173 patients (34 with activating EGFR mutations, 13 who were positive for ALK translocation) were enrolled, and the median follow-up duration was 36 months (range, 3-123 months). The 3-year overall survival rate was significantly higher in the EGFR-mutant group than in the wild-type EGFR group (75% vs. 46%; P ¼ .002). There was a tendency towards a better overall survival in the ALK-positive group than in the ALK-negative group (68% vs. 44%; P ¼ .085). No differences in the 3-year progression-free survival were observed according to the EGFR or ALK status. The EGFR-mutant group showed a significantly lower rate of in-field failure (P ¼ .027) and higher rate of out-of-field failure (P ¼ .029) as compared with the wild-type EGFR group. There was no significant difference in the rate of in-field failure or out-of-field failure between the ALK-positive and ALK-negative groups. Conclusions: Although the ALK-positive group showed no characteristic failure pattern, the EGFR-mutant group showed a lower rate of in-field failure and higher rate of out-of-field failure.

Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are low at 11-25%, resulting in 9-10 months of median overall survival (OS). An improved therapeutic efficacy by combining immunotherapy with radiation has been reported in patients with locally advanced non-small cell lung cancer. The results using ESCC cell lines suggest sequential treatment with anti-PD-L1 agents soon after completion of CRT is the most effective combination.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Objective:The aims of this study were to investigate the frequency of symptomatic radiation pneumonitis (RP) after CyberKnife lung stereotactic body radiotherapy (SBRT) and to evaluate predictive factors of symptomatic RP.Methods:56 patients with peripheral non-small-cell lung cancer were treated using the CyberKnife® VSI™ System (Accuracy Inc., Sunnyvale, CA) between May 2013 and September 2015. Total radiation doses ranged from 48 to 56 Gy, as delivered in four equal fractions. Symptomatic RP was defined as a grade of ≥2. Predictive factors for symptomatic RP were evaluated using univariate and multivariate analyses.Results:With a median follow-up duration of 12.5 months (range, 3–27 months), symptomatic RP was observed in 6 (10.7%) of the 56 patients. In the univariate analysis, percent vital capacity (p < 0.05), maximum tumour diameter (p < 0.05), gross tumour volume (p < 0.05), planning target volume (p < 0.01), mean lung dose (p < 0.01) and a normal lung volume receiving 5–50 Gy of radiation (V5–50) (p < 0.01) were identified as significant predictive factors for symptomatic RP. In the multivariate analysis, only a V25 >3.4% (p = 0.011) was identified as a significant predictive factor of symptomatic RP.Conclusion:The incidence of symptomatic RP after CyberKnife SBRT was almost identical to the incidences reported in the linear accelerator-based SBRT. A significant association was observed between a V25 >3.4% and the risk of developing symptomatic RP.Advances in knowledge:This is the first report that has investigated prognostic factors for symptomatic RP after CyberKnife SBRT for lung cancer. The newly developed scoring system may help to predict symptomatic RP.

Bullfrog sympathetic ganglion cells produced hyperpolarizing(Ad-hyperpolarization)and depolarizing(Ad-depolarization)responses when adrenaline(Ad)was directly applied to ganglia. MARRAZZI(1939)originally demonstrated the inhibitory action of adrenaline (Ad)on transmission in the superior cervical ganglion,and the possibility that catecholamines may be acting as a neurotransmitter in sympathetic ganglia has

Purpose To investigate clinical characteristics of RDH5 -related fundus albipunctatus (FAP) in a Japanese cohort. Methods Twenty-five patients from 22 pedigrees with RDH5 -related FAP were studied. Ophthalmic medical records were reviewed. For genetic analysis, either Sanger sequencing of the RDH5 gene or whole-exome sequencing was performed. Results Genetic analysis identified eight different RDH5 variants, including seven known RDH5 variants (p.G35S, p.G107R, p.R167H, p.A240GfsX19, p.R278X, p.R280H, and p.L310delinsEV) and a novel variant: c.259C>T (p.Q87X). The most frequently observed variant was p.L310delinsEV (65.2%, 30/46 alleles). Of 50 eyes examined, 44 eyes (88.0%) showed logMAR best-corrected visual acuity (BCVA) of 0.10 or better. In optical coherence tomography, macular involvement was observed in 12 patients (24 eyes). Ten patients (83.3%) who had good BCVA (0.10 or better) exhibited diffuse disruption of the outer retina with foveal sparing, and two patients (16.7%) exhibited diffuse disruption throughout the macula and decreased BCVA. Among the 24 eyes, ring-or crescent-shaped hyperautofluorescence or irregular autofluorescence around the fovea was observed in 15 eyes (83.3%) of 18 eyes examined by fundus autofluorescence imaging. Full-field electroretinography showed extinguished or severely decreased rod responses in all 23 examined patients, whereas decreased cone responses were seen in 17 patients (73.9%). Conclusions Multimodal imaging and electroretinography of RDH5 -related FAP revealed high frequencies of macular involvement in older patients and decreased cone responses. Our findings suggest that progressive macular/cone dysfunction, as well as delayed rod function, may be key phenotypic features of RDH5 -related FAP.