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Prevention of preterm birth (PTB) is a global challenge and is one of the most important issues to be addressed in perinatal care. The hypothesis that ascending lower genital infection leads to PTB has been tested in numerous in vitro and in vivo studies. For patients with intractable vaginitis or high-risk patients with successive PTBs, mainly due to intra-uterine infection, the vaginal flora is enhanced to increase systemic immunity and locally propagate Lactobacillus species. It has been shown that the administration of lactoferrin (LF), a prebiotic with minimum side effects, may be effective in suppressing PTB. This hypothesis has been evaluated in this review using various relevant test examples. The findings suggest that LF may play a role in inflammatory protection in pregnant human cervical tissue. The antibacterial and anti-cytokine effects of LF in human-derived mucus-producing cervical cell lines were also demonstrated. It was also clarified that LF suppresses PTB and improves the prognosis of pups in inflammation-induced PTB animal models. Thus, we have identified that LF, a prebiotic contained in breast milk, can be clinically applied to suppress PTB in humans and to prevent PTBs in high-risk pregnancies.

Increasing the T-cell immune response to Mycobacterium tuberculosis with an anti-programmed cell death 1 (anti-PD-1) antibody may ultimately have detrimental effects. We present the case of a patient with advanced non-small cell lung cancer who developed active tuberculosis (TB) after initial treatment with pembrolizumab, an anti-PD-1 antibody. Pembrolizumab was resumed after completing anti-TB treatment, and no relapse of TB was observed clinically or radiologically. Checkpoint inhibitor-related pneumonitis (CIP) is first suspected when a pulmonary shadow presents during treatment with an anti-PD-1 antibody. It is sometimes difficult to diagnose CIP using computed tomographic images alone. Careful testing, including bacterial examinations and bronchoscopic biopsy, should be performed.

The comparison of distant atomic clocks is foundational to international timekeeping, global positioning and tests of fundamental physics. Optical-fibre links allow the most precise optical clocks to be compared, without degradation, over intracontinental distances up to thousands of kilometres, but intercontinental comparisons remain limited by the performance of satellite transfer techniques. Here we show that very long baseline interferometry (VLBI), although originally developed for radio astronomy and geodesy, can overcome this limit and compare remote clocks through the observation of extragalactic radio sources. We developed dedicated transportable VLBI stations that use broadband detection and demonstrate the comparison of two optical clocks located in Italy and Japan separated by 9,000 km. This system demonstrates performance beyond satellite techniques and can pave the way for future long-term stable international clock comparisons. Very long baseline interferometry is used to compare two optical clocks located in Japan and Italy through the observation of extragalactic radio sources. This approach overcomes limitations of the performance of satellite transfer techniques.

We have developed a broadband VLBI (very long baseline interferometry) system inspired by the concept of the VLBI Global Observing System (VGOS). The new broadband VLBI system was implemented in the Kashima 34 m antenna and in two transportable stations utilizing 2.4 m diameter antennas. The transportable stations have been developed as a tool for intercontinental frequency comparison but are equally useful for geodesy. To enable practical use of such small VLBI stations in intercontinental VLBI, we have developed the procedure of node-hub style VLBI: In joint observation with a large, high sensitivity ‘hub’ antenna, the closure delay relation provides a virtual delay observable between ‘node’ stations. This overcomes the limited sensitivity of the small diameter node antennas, while error sources associated with large diameter antennas, such as gravitational deformation and delay changes in necessarily long signal cables, are eliminated. We show that this scheme does not result in an increased sensitivity to radio source structure if one side of the baseline triangle is kept short. We have performed VLBI experiments utilizing this approach over both short range and intercontinental distance. This article describes the system components, signal processing procedure, experiment, and results in terms of baseline repeatability. Our measurements reveal signatures of structure effects in the correlation amplitude of several of the observed radio sources. We present a model of the frequency-dependent source size for 1928+738 derived from correlation amplitude data observed in four frequency bands.

For the aim to enable precise frequency transfer over earth radius scale distance, NICT developed a broadband VLBI system observing 3-14 GHz radio frequency range, and that was implemented in a pair of transportable 2.4m diameter VLBI stations and Kashima 34m diameter VLBI station. The small diameter VLBI stations installed in Medicina observatory of INAF (Italy) and NICT headquarters in Koganei (Japan) were used compare the atomic frequency standards. The poor sensitivity of VLBI observation with the small antenna pair was compensated by participation of the large diameter antenna for boosting the signal to noise ratio (SNR) of the VLBI observation. Owing to the broad observing frequency range, a few pico seconds precision of group delay is achieved on intercontinental baseline even with small diameter antenna. Advanced digital data acquisition with highspeed 16 GHz sampling enabled stable group delay measurement. A series of frequency transfer experiments was conducted during Oct. 2018 – Feb. 2019 by using the broadband VLBI system between ytterbium (Yb) optical lattice clock of INRiM (Italy) and strontium (Sr) lattice clock of NICT(Japan) separated by 9000km. The deviation of fractional frequency ratio between Yb and Sr was obtained by VLBI observation as y(Yb/Sr)=2.5(2.8)x10-16. The uncertainty in this experiment is evaluated not to be limited by the VLBI link itself, and further improvement is expected. Prospect of VLBI frequency link and uncertainty budget in VLBI observation is discussed in this report.

8536 Background: Concurrent chemoradiotherapy followed by durvalumab maintenance for up to 12 months is the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, the best timing of starting durvalumab after completion of chemoradiation has not been identified. Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after last radiation to randomization according to the PACIFIC study (Antonia SJ, et al. 2017, 2018 NEJM). Methods: This study was a prospective, single-arm, multicenter, phase II clinical trial. Eligibility criteria included patients with unresectable stage III NSCLC, ECOG PS 0-1, age < 75 years old. Patients who did not have disease progression after definitive concurrent chemoradiotherapy (CCRT) (chemotherapy: 2 cycles of platinum-based doublet chemotherapy, radiotherapy: 60 Gy/30 Fr) received durvalumab (10 mg/kg, every 2 weeks for up to 12 months) from the next day (allowed up to 5 days) after last radiation. The primary endpoint was 1-year PFS rate from registration assessed by an independent review committee. The planned sample size was 47 with a threshold value of 50% based on results of the PACIFIC study, an expected value of 63%, one-sided alpha of 20% and power of 80% in 1-year PFS rate. Results: From January 2020 to August 2020, 50 patients were enrolled from 16 institutions and 47 patients were evaluable for efficacy and safety. Forty-two patients received durvalumab maintenance therapy. Patient characteristics were: male/female 41/6; median age 65 (range 42-75); ECOG PS 0/1 28/19; IIIA/IIIB/IIIC 19/21/7. The 1-year PFS rate from registration was 75.0% (60% CI: 69.0 to 80.0). The 1-year OS rate from registration was 97.7% (95%CI: 84.6 to 99.7). ORR, median PFS and median OS were 78.7%, 14.2 months (95%CI: 13.4 to not reached (NR)) and NR, respectively. Grade 3/4 adverse events were pneumonitis (4.3%), neutropenia (44.7%), febrile neutropenia (4.3%). There was no treatment-related death. Conclusions: Our study met the primary endpoint. Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity occurred as a reference to the PACIFIC study. Clinical trial information: jRCTs031190117.

Background Anti‐programmed death‐1 (PD‐1) immunotherapy can cause immune‐related pneumonitis, also known as checkpoint inhibitor pneumonitis (CIP). CIP that develops early after the initiation of anti‐PD‐1 immunotherapy is important because it is more severe than CIP that develops later. However, only a few studies have examined the risk factors for early‐onset CIP. Previous studies have reported several risk factors for CIP, including imaging findings of airway obstruction adjacent to lung tumors. However, the utility of this factor is debatable. Therefore, we investigated potential risk factors for early‐onset CIP, including tumor invasion in the central airway (TICA), in patients with non‐small cell lung cancer (NSCLC) receiving anti‐PD‐1 therapy. Methods We retrospectively analyzed the medical records and chest computed tomography scans of patients with NSCLC treated with anti‐PD‐1 antibodies at the Kanagawa Cancer Center in Japan between 1 January 2016, and 30 June 2018. The clinical characteristics and imaging findings, including TICA, were compared between patients with and without early‐onset CIP. Results Data from 181 eligible patients (114 receiving nivolumab and 67 receiving pembrolizumab) were analyzed. Early‐onset CIP occurred in 13 of 79 patients (16.5%) with TICA and 2 of 102 patients (2.0%) without TICA. In multivariate analysis, the odds ratio of early‐onset CIP for patients with TICA was 8.2 (95% confidence interval [CI]: 1.98–34.0, P = 0.0037). Conclusions TICA was strongly associated with early‐onset CIP in patients with NSCLC. Clinicians should carefully observe patients with TICA, especially within three months of anti‐PD‐1 antibody administration because of high CIP risk. Key points Significant study findings Tumor invasion in the central airway (TICA) was a predictor of early‐onset checkpoint inhibitor pneumonitis (CIP)TICA had good interobserver variability, indicating its utility in clinical practicePatients with TICA might have a higher immune status than patients without What this study adds This is the first study focusing on risk factors for CIP limited to early‐onset CIP., TICA was strongly associated with early‐onset CIP in patients with NSCLC. Clinicians should carefully observe patients with TICA, especially within three months of anti‐PD‐1 antibody administration because of high CIP risk.

This paper presents the local correlation method of low-SNR (Signal to Noise Ratio) and strongly RFI (Radio Frequency Interference) contaminated DOR (differential one-way ranging) signals with Chin...

Although programmed death (PD)-1 immune checkpoint therapies target the immune system, the relationship between inflammatory factors and the clinical outcome of anti-PD-1 therapy for nonsmall cell lung cancer (NSCLC) is not fully understood. Here we examined the association between soluble immune mediators and the outcome of treatment with PD-1 inhibitors in patients with advanced/recurrent NSCLC. In two independent cohorts, we assessed the levels of 88 different soluble immune mediators in peripheral blood before and after anti-PD-1 treatment, and evaluated their associations with clinical outcomes. In the training cohort, the plasma levels of chitinase 3-like-1 and GM-CSF before treatment (p = 0.006 and p = 0.005, respectively) and changes in the plasma levels of CXCL2, VEGF, IFNα2, and MMP2 after treatment (p < 0.001, p = 0.019, p = 0.019, and p = 0.012, respectively) were significantly correlated with PFS. The change in the plasma CXCL2 level was also significantly associated with treatment-related AEs (p = 0.017). In the validation cohort, however, only the changes in the plasma levels of CXCL2 and MMP2 after treatment were associated with PFS (p = 0.003 and p = 0.006, respectively), and these changes were maintained during the course of anti-PD-1 therapy in patients who showed better clinical outcomes, even in those with tumor pseudoprogression. Since CXCL2 and MMP2 can be easily measured by minimally invasive blood sampling, they could be useful for monitoring of clinical outcomes in NSCLC patients receiving PD-1 inhibitor therapy.

Cisplatin-based chemotherapy is the standard adjuvant therapy for patients with completely resected stage II or III non-small cell lung cancer (NSCLC). However, the completion rate of four cycles of cisplatin-based chemotherapy is about 50%. This phase II study was conducted to evaluate the tolerability and efficacy of nedaplatin and irinotecan as adjuvant chemotherapy. Patients with pathological stage II or III NSCLC who underwent complete resection were enrolled. Treatment consisted of four cycles of nedaplatin (50 mg/m2) and irinotecan (50 mg/m2) on days 1 and 8 every 4 weeks. The primary end-point was the completion rate of four cycles of nedaplatin and irinotecan. Between January 2009 and March 2012, 39 patients (23 males and 16 females; median age 68 years) were registered. Overall, 36/39 (92.3%) patients completed four cycles. The median clinical follow-up time was 56 months (range 11–88 months). There were no differences in adverse events between patients with UGT1A1 polymorphisms and patients with wild-type UGT1A1. The median disease-free survival (DFS) was 49.4 months (95% confidence interval 14.2–84.5 months). Median overall survival (OS) was not reached. There were no treatment-related deaths, and adverse events were acceptable. The 5-year DFS and OS rates were 43.1 and 69.8%, respectively. Nedaplatin and irinotecan is a tolerable regimen for adjuvant chemotherapy, and was associated with adequate 5-year DFS and OS rates.

High precision distant frequency transfer techniques are desired to compare the advanced atomic frequency standards (AFS), which are newly developed by metrological research institutes in the world. Fiber-link frequency transfer is the technique of current highest highest accuracy, although distance of comparison is limited by fiberlink. Two-way satellite time and frequency transfer (TWSTFT) is the technique used for high precision time and frequency transfer. Its drawbacks are dependency on geographical availability of satellite and running cost including transponder of satellite, radio signal transmission license. Space geodetic techniques such as Global Navigation Satellite Systems (GNSS) and Very Long Baseline Interferometry (VLBI) observations are passive method as the next choices for time and frequency transfer. VLBI observation determines the spatial coordinates of the station and clock difference simultaneously. The analysis is theoretically based on inertial reference frame using natural radio source fixed in celestial sphere. These features have advantages of VLBI in the aspect of long term stability of comparison than the other space techniques which uses artificial signal sources. We have developed a broadband VLBI system named GALA-V [1], which is designed for advanced delay precision with observing broad observation frequency range (3-14GHz).

A sufficiently large tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥1 mm2) and tumor content rate (≥30%) on the success rate of the Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

Introduction The purpose of this study was to evaluate the natural course of the progression of pulmonary subsolid nodules (SSNs). Materials and Methods Eight facilities participated in this study. A total of 795 patients with 1229 SSNs were assessed for the frequency of invasive adenocarcinomas. SSNs were classified into three categories: pure ground-glass nodules (PGGNs), heterogeneous GGNs (HGGNs) (solid component detected only in lung windows), and part-solid nodules. Results The mean prospective follow-up period was 4.3 ± 2.5 years. SSNs were classified at baseline as follows: 1046 PGGNs, 81 HGGNs, and 102 part-solid nodules. Among the 1046 PGGNs, 13 (1.2%) developed into HGGNs and 56 (5.4%) developed into part-solid nodules. Among the 81 HGGNs, 16 (19.8%) developed into part-solid nodules. Thus, the SSNs at the final follow-up were classified as follows: 977 PGGNs, 78 HGGNs, and 174 part-solid nodules. Of the 977 PGGNs, 35 were resected (nine minimally invasive adenocarcinomas [MIAs], 21 adenocarcinomas in situ [AIS], and five atypical adenomatous hyperplasias). Of the 78 HGGNs, seven were resected (five MIAs and two AIS). Of the 174 part-solid nodules, 49 were resected (12 invasive adenocarcinomas, 26 MIAs, 10 AIS, and one adenomatous hyperplasia). For the PGGNs, the mean period until their development into part-solid nodules was 3.8 ± 2.0 years, whereas the mean period for the HGGNs was 2.1 ± 2.3 years ( p = 0.0004). Conclusion This study revealed the frequencies and periods of development from PGGNs and HGGNs into part-solid nodules. Invasive adenocarcinomas were diagnosed only among the part-solid nodules, corresponding to 1% of all 1229 SSNs.

Aim With the advent of the molecular-targeted therapy, rapid progress has been made in the treatment of advanced or recurrent non-small-cell lung cancer (NSCLC). Although surgical complete resection remains the standard and most promising treatment, the clinical significance of epidermal growth factor receptor (EGFR) gene mutations in early-stage NSCLC remains uncertain. Methods We investigated the prognostic value of EGFR mutations in surgically resected pathological stage I NSCLC. A total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method. Results Mutations of EGFR were detected in 185 of the 388 patients (47.7%). EGFR mutations were more frequently found in women (110 of 185, 59.5%), adenocarcinoma (183 of 185, 98.9%), patients with no vascular invasion (139 of 185, 75.1%) and nonsmokers (106 of 185, 57.3%). In patients with pathological stage I adenocarcinoma, both overall survival (OS) and disease-free survival (DFS) were significantly higher in patients with EGFR mutation than in those with wild-type EGFR. Furthermore, patients with exon 21 mutation have better DFS than those with exon 19 mutation in stage IB adenocarcinoma. Cox's proportional hazard model indicated that EGFR status was an independent variable for predicting the OS and DFS in patients with pathological stage IB adenocarcinoma. Conclusion Our results suggest that EGFR mutations might be a prognostic factor in patients with pathological stage I lung adenocarcinoma.

Continuation maintenance therapy with pemetrexed (PEM) and bevacizumab (BEV) following induction therapy with cisplatin (CDDP), PEM, and BEV is beneficial in advanced non-squamous non-small-cell lung cancer (NS-NSCLC), but the survival benefit of addition of BEV to CDDP/PEM as induction therapy is still unclear. The aim of this phase II study was to evaluate the feasibility and safety of a CDDP/PEM/BEV regimen in Japanese patients with EGFR wild-type NS-NSCLC.This study included 25 patients who receive intravenous CDDP, PEM, and BEV (15 mg/kg) from August 2010 to February 2013. The primary endpoint of this study was the response rate (RR) and the secondary endpoint was progression free survival (PFS), overall survival (OS), and safety.The median cycles of induction chemotherapy were four (range 1-6). RR was 64%. Most patients (64%) transitioned to maintenance therapy. The median PFS was 9.7 months. Median OS was 21.6 months. Haematological adverse events reaching grade 3 to 4 were neutropenia (8%) without febrile neutropenia, thrombocytopenia (4%), and anemia (4%). BEV-related non-haematological toxicities of grade 3/4 were hypertension (16%), thrombosis (4%), and gastrointestinal perforation (4%). Each adverse events was controllable, and there were no treatment-related deaths.CDDP/PEM/BEV regimen is effective and tolerable in patients with EGFR wild-type advanced NS-NSCLC, but should be paid attention to some BEV-related toxicities.

Although programmed death (PD)-1 immune checkpoint therapies target the immune system, the relationship between inflammatory factors and the clinical outcome of anti-PD-1 therapy for nonsmall cell lung cancer (NSCLC) is not fully understood. Here we examined the association between soluble immune mediators and the outcome of treatment with PD-1 inhibitors in patients with advanced/recurrent NSCLC. In two independent cohorts, we assessed the levels of 88 different soluble immune mediators in peripheral blood before and after anti-PD-1 treatment, and evaluated their associations with clinical outcomes. In the training cohort, the plasma levels of chitinase 3-like-1 and GM-CSF before treatment (p = 0.006 and p = 0.005, respectively) and changes in the plasma levels of CXCL2, VEGF, IFNα2, and MMP2 after treatment (p0.001, p = 0.019, p = 0.019, and p = 0.012, respectively) were significantly correlated with PFS. The change in the plasma CXCL2 level was also significantly associated with treatment-related AEs (p = 0.017). In the validation cohort, however, only the changes in the plasma levels of CXCL2 and MMP2 after treatment were associated with PFS (p = 0.003 and p = 0.006, respectively), and these changes were maintained during the course of anti-PD-1 therapy in patients who showed better clinical outcomes, even in those with tumor pseudoprogression. Since CXCL2 and MMP2 can be easily measured by minimally invasive blood sampling, they could be useful for monitoring of clinical outcomes in NSCLC patients receiving PD-1 inhibitor therapy.

Background Preclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Methods Eligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC. The patients received 4 cycles of docetaxel (60 mg/m2), cisplatin (80 mg/m2), and bevacizumab (15 mg/kg) once every 3 weeks, followed by bevacizumab as maintenance therapy, every 3 weeks until disease progression or attainment of unacceptable toxicity level. The primary endpoint was objective response rate (ORR). The numbers of circulating endothelial cells (CEC) were also estimated on days 1 and 8 of the first cycle for the exploratory analysis of efficacy prediction. Results A total of 47 patients were enrolled from October 2010 to April 2012. Bevacizumab as maintenance therapy was administered to 41 patients (87.2%), and the median number of total treatment cycles was 9 (range: 1–36). ORR, median progression-free survival (PFS), and median overall survival of the patients were 74.5%, 9.0 months, and 27.5 months, respectively. The most common grade 3/4 adverse event was neutropenia (95.7%), followed by leukopenia (59.6%) and hypertension (46.8%). PFS was longer in patients with ≥10 count increase in CECs than that in patients with

Background Palpation is the most important means of locating lung tumors and resecting them with sufficient margins. This study aimed to predict the palpability of pulmonary lesions using high-resolution computed tomography. Methods Eighty-six pulmonary lesions were palpated in fresh resected lung specimens from July 2013 to March 2014. The following parameters were compared between 10 impalpable and 76 palpable lesions: maximum tumor size in pulmonary and bone window level settings, consolidation tumor size in pulmonary window level setting, and pleural-tumor distance. In 54 adenocarcinomas, the lepidic component and fibrosis foci rates were compared between the two groups. Results Tumor size in bone window level setting and the consolidation tumor size were significantly smaller in the impalpable group (both p Conclusions Tumor size in bone window level setting or a consolidation tumor size ≤5 mm and pleural-tumor distance ≥ 5 mm are simple criteria that are potentially useful indicators for preoperative marking to locate small-sized lepidic-predominant adenocarcinomas with few fibrotic foci.

For the sake of high-sensitivity 6.7 GHz methanol maser observations, we developed a new technology for coherently combining the two signals from the Hitachi 32 m radio telescope and the Takahagi 32 m radio telescope of the Japanese Very long baseline interferometer Network (JVN), where the two telescopes were separated by about 260 m. After the two telescopes were phased as a twofold larger single telescope, the mean signal-to-noise ratio (SNR) of the 6.7 GHz methanol masers observed by the phased telescopes was improved to 1.254-fold higher than that of the single dish, through a Very Long Baseline Interferometry (VLBI) experiment on the 50 km baseline of the Kashima 34 m telescope and the 1000 km baseline of the Yamaguchi 32 m telescope. Furthermore, we compared the SNRs of the 6.7 GHz maser spectra for two methods. One is a VLBI method and the other is the newly developed digital position switching, which is a similar technology to that used in noise-cancelling headphones. Finally, we confirmed that the mean SNR of method of the digital position switching (ON-OFF) was 1.597-fold higher than that of the VLBI method., Comment: 17 pages, 10 figures, accepted for publication in Publications of the Astronomical Society of the Pacific (PASP)

An association between UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphisms and irinotecan-induced neutropenia has been previously reported. In this study, we assessed the clinical usefulness of testing for UGT1A1 polymorphisms prior to the initiation of irinotecan-based chemotherapy, as this remains a controversial subject. A total of 136 lung cancer patients who were treated with a combination of nedaplatin and irinotecan as initial chemotherapy were assessed. Following exclusion of patients exhibiting low UGT1A1 enzyme activity, 70 patients were treated after UGT1A1 polymorphism testing (test group) and 66 patients were treated without UGT1A1 polymorphism testing (non-test group). We retrospectively analyzed and compared the adverse events between the test and the non-test groups and observed no reduction in hematological or non-hematological toxicities in the test group compared to that in the non-test group. Of the 9 patients with grade 4 or 5 non-hematological toxicity, 6 patients had febrile neutropenia (FN). All the patients with FN were aged >70 years. The incidence of adverse events was significantly higher among patients aged >70 years compared to that among younger patients. In conclusion, in patients treated with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism testing prior to the initiation of chemotherapy did not reduce the incidence of adverse events. Therefore, UGT1A1 polymorphism testing alone may not be sufficient to predict the occurrence of severe adverse events and it may be more important to effectively manage adverse events, particularly in elderly patients.

Background The prognostic value of maximum standardized uptake value (maxSUV) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is known for localized pulmonary adenocarcinoma, which is most commonly non-mucinous adenocarcinoma. We examined the validity of thin-section computed tomography (TS-CT) and FDG-PET findings in mucinous adenocarcinoma. Materials and Methods TS-CT and FDG-PET were performed on 25 patients with mucinous lung adenocarcinoma that was subsequently resected between January 2009 and March 2013. Based on the percentage reduction of maximum tumor diameter on the mediastinal window image compared with the diameter on the lung window image on TS-CT, tumors were classified as air-type (≥50%) or solid-type ( Results Most mucinous adenocarcinomas were located in the lower lobe. All except two were classified as solid-type tumor on TS-CT. Multiple regression analysis revealed the correlation of maxSUV with pathological tumor size and diameter of pathological invasive area; these two parameters showed no significant correlation with each other (r = 0.354, p = 0.083). maxSUV was significantly lower for tumors with invasive area ≤5 mm than for tumors with invasive area >5 mm (1.62 vs. 3.77, p = 0.01), but no statistically significant difference was found in terms of other pathological invasive findings such as the presence of lymphatic or vascular invasion, pleural involvement, or predominant histological subtype. Conclusions Most mucinous adenocarcinomas had appearances of solid-type tumor on TS-CT. maxSUV on FDG-PET indicates the pathological invasive area in mucinous adenocarcinoma as well as non-mucinous adenocarcinoma.

Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth.We conducted a phase I/II study of Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks.Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1 administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0%. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60%.Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.

We conducted a phase II study of nedaplatin (NP) and irinotecan (CPT) with concurrent thoracic radiotherapy (TRT) followed by docetaxel for locally advanced non-small cell lung cancer (NSCLC) to determine the safety and efficacy of the treatment. Patients with stage IIIA or IIIB NSCLC were treated with 3 cycles of chemotherapy comprising NP at 50 mg/mFifteen patients were registered, and 8 were able to receive the entire treatment regimen. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 1 patient, respectively, receiving NP and CPT with concurrent TRT. Major non-hematological toxicities were nausea, vomiting and fatigue. Grade 3 pneumonitis and esophagitis occurred in one patient each, and 4 patients developed febrile neutropenia. Docetaxel consolidation was associated with mild toxicities. Two patients died of late pulmonary failure 3 to 4 months after treatment completion, and the study was terminated. Twelve patients responded, and the median survival time, and the 1-year and 3-year survival rates were 39.3 months, 86.7% and 60.0%, respectively. In conclusion, NP and CPT with concurrent TRT is effective for patients with locally advanced NSCLC, but frequently induces pulmonary damage.

We report on a very long baseline interferometry (VLBI) experiment on giant radio pulses (GPs) from the Crab pulsar in the radio 1.4 to 1.7 GHz range to demonstrate a VLBI technique for searching for fast radio bursts (FRBs). We carried out the experiment on 26 July 2014 using the Kashima 34 m and Usuda 64 m radio telescopes of the Japanese VLBI Network (JVN) with a baseline of about 200 km. During the approximately 1 h observation, we could detect 35 GPs by high-time-resolution VLBI. Moreover, we determined the dispersion measure (DM) to be 56.7585 +/- 0.0025 on the basis of the mean DM of the 35 GPs detected by VLBI. We confirmed that the sensitivity of a detection of GPs using our technique is superior to that of a single-dish mode detection using the same telescope., 10 pages, 4 figures, accepted for publication in Publications of the Astronomical Society of the Pacific

We carry out an error analysis of 24-hour global positioning system (GPS)-very long baseline interferometry (VLBI) (GV) hybrid observation data. In this paper, we focus on the impacts of broadcast and final orbits on the GPS delays of the GV hybrid observation by analyzing the residuals, observed - calculated (O-C) values. The residuals show apparent and consistent biases for L1 and L2 signals, respectively. The scatters of the residuals are around a few nanoseconds. The main cause of those observation errors is the absence of the GPS phase and delay calibration system. Most of the satellites show that the differences between the delays, to which broadcast and final orbits are applied, are about 100 times smaller than the current GV hybrid observation errors. We conclude that GPS delays are not greatly affected by orbit accuracies.

Radio frequency (RF) direct sampling is a technique used to sample RF signals that are higher than the sampling rate, without the use of a frequency converter and an anti-aliasing filter. In the case of geodetic VLBI, the RF frequency is at most 9 GHz. Recently, a digital sampler with high sensitivity at RF frequencies greater than 10 GHz was developed. The sampler enables us to evaluate the use of the RF direct sampling technique in geodetic VLBI. RF direct sampling has the potential to make the system simple and stable because, unlike a conventional system, analog frequency converters are not used. We have developed two sets of RF direct sampling systems and operated them on Kashima and Tsukuba baseline (about 50 km length) in Japan. At first, we carried out the VLBI experiment only for X band (8 GHz) signals and successfully got the first fringes. Aliased signals could be discriminated through correlation processing. Then, we adopted RF direct sampling for mixed signals, i.e., S band (2 GHz) and X band signals are combined with each other to make a geodetic VLBI observation. We carried out a 24 hr geodetic VLBI session on 2011 October 19 and succeeded in fringe detection for both S and X bands. After correlation processing, baseline analysis was carried out and we got results consistent with those obtained by conventional VLBI.

There have been reports on the use of erlotinib in non-small cell lung cancer (NSCLC) patients after gefitinib resistance occurs, and it has been stated that erlotinib may be beneficial in patients with long stable disease (SD) previously treated with gefitinib.We retrospectively studied gefitinib-resistant NSCLC patients with favorable clinical features, who received erlotinib following disease progression after gefitinib treatment of more than 6 months.A total of 21 patients with NSCLC were included. Partial response was seen in 2 cases (9%), SD in 6 cases (19%), and progressive disease (PD) in 13 cases (62%). Disease control (DC) was achieved with erlotinib in 8 cases (36%). The median survival time (MST) was 369 days in DC cases and 133 days in PD cases. There were no statistical differences between DC cases and PD cases in terms of MST relative to sex, smoking and skin rash.Subsequent erlotinib therapy is one of the therapeutic options in the treatment of gefitinib-resistant NSCLC in which prior gefitinib has shown long-term SD of more than 6 months.

We divided pulmonary adenocarcinoma of ≤ 20 mm into air-containing and solid-density types based on a percentage reduction of the maximum tumor diameter in the mediastinal window image compared to the area in the lung window image on thin-section (TS) CT of ≥ 50% (air-containing type) and50% (solid-density type). No relapse occurred in patients with air-containing type. The prognosis of solid-density type may be poor even when the tumor size is 20mm or smaller. We investigated whether CT findings for these tumors could serve as prognostic factors.The subjects were 105 patients with solid-density type pulmonary adenocarcinoma that was identified on TSCT and found to have a diameter of 20mm or smaller after surgical resection during the period from April 1997 to November 2004. Notches, air bronchogram, pleural retraction, spiculation, venous involvement, and ground glass opacity were examined on TSCT, and their associations with pathological findings (i.e., pleural invasion, lymphatic permeation, vascular invasion, lymph node metastasis, and Noguchi's classification) and relapse were investigated using chi-square test and Cox proportional hazards model.The incidence of relapse was significantly higher in cases with notches. The incidence of notches increased with tumor growth and notches were frequent in Noguchi type D tumors, reflecting poorly differentiated adenocarcinoma. Lymphatic permeation and type D cases were independent factors associated with a poor prognosis using Cox proportional hazards model.TSCT findings may be useful for prediction of the prognosis of solid-density type pulmonary adenocarcinoma.