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Background A randomized, controlled trial to evaluate the superiority of peritoneovenous shunt (PVS) over the other treatments for refractory ascites in advanced cancer patient was conducted. Subjects and methods The subjects were advanced cancer patients with symptoms due to refractory ascites which are difficult to control by medical therapy and cannot be improved by methods other than drainage and with a Palliative Prognostic Index of Results Forty patients were enrolled between November 2009 and July 2018, with 20 allocated to test group and 20 control group. The mean AUC of the symptom improvement score curves were 133.2 (95% CI: 98.6-167.7) in the test group and 69.9 (95% CI: 34.4-105.4) in the control group (p=0.014). Therefore, the mean AUC was significantly larger in the test group, resulting the primary endpoint was met. There was no significant difference between the groups in SF-8 and EQ-5D. Though some known adverse events were observed, there was no significant difference in the frequency of individual adverse events between the groups. Conclusions PVS significantly improves the symptom of pain due to refractory ascites compared to other treatments. Although not as effective as improving the comprehensive QOL evaluated with SF-8 and EQ-5D, PVS may be considered the standard of care for advanced cancer patients with refractory ascites.

Objective Many clinical trials for older patients with metastatic colorectal cancer have been conducted, and fluoropyrimidine and bevacizumab are standard treatments. However, the relationship between age and the efficacy and safety of this treatment is unclear in older metastatic colorectal cancer patients. Methods Individual data from two phase II studies on older (≥75 years), non-frail patients with metastatic colorectal cancer treated with uracil-tegafur/leucovorin or S-1 combined with bevacizumab were collected. Patient characteristics were evaluated with multiple regression analyses for survival outcomes, using the Cox proportional hazard model and linear regression analyses for the worst grade of adverse events. Results We enrolled 102 patients with a median age of 80 years (range, 75–88 years). Of the 70 patients who died, seven (10%) died of causes unrelated to disease or treatment. The study treatment was discontinued due to adverse events in 19 patients (18.6%), with 63% aged ≥85 years. The adverse event that most commonly resulted in treatment discontinuation was grade 2 fatigue (21%). Chronological age was not associated with progression-free survival (Hazard ratio, 1.03; P = 0.40) or overall survival (Hazard ratio, 1.02; P = 0.65). Age was weakly associated with non-hematologic adverse events (regression coefficient [R], 0.27; P = 0.007), especially fatigue (R, 0.23; P = 0.02) and nausea (R, 0.19; P = 0.06), but not with hematologic (R, 0.05; P = 0.43) or bevacizumab-related (R, −0.06; P = 0.56) adverse events. Conclusions The efficacy of fluoropyrimidine plus bevacizumab was age-independent in patients with metastatic colorectal cancer aged ≥75 years, and attention should be paid to non-hematologic adverse events as age increases.

Objective Fibroblast growth factor receptor 2 (FGFR2) has been proposed as a novel druggable target in unresectable gastric cancer. FGFR2 alteration has been reported as associated with poor prognosis even in patients with gastric cancer who received systemic chemotherapy. This study aimed to evaluate the frequency of FGFR2 overexpression and gene amplification in clinical specimens from Japanese patients with recurrent or unresectable gastric cancer. Methods This observational study enrolled patients who were histologically or cytologically confirmed with unresectable HER2-negative or unknown gastric or gastroesophageal junctional adenocarcinoma treated with at least one previous chemotherapy. FGFR2 overexpression and gene amplification in the specimens were evaluated by immunohistochemical staining and fluorescence in situ hybridization methods, respectively. Results In a total of 173 eligible cases, FGFR2 immunohistochemistry score was evaluated as 0, 1, 2, 3 and 4 for 20, 80, 35, 28 and 10 cases, respectively. In 151 evaluable cases with FGFR2 immunohistochemistry scores of 1–4, FGFR2 copy number expressed as fluorescence in situ hybridization signals were detected as, A multicenter study evaluating the frequency of fibroblast growth factor receptor 2 overexpression and gene amplification in tumor specimen from Japanese patients with recurrent or unresectable gastric cancer.

Background The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS). Conclusion Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

The amino acid sequence of the OCC_10945 gene product from the hyperthermophilic archaeon Thermococcus litoralis DSM5473, originally annotated as γ-aminobutyrate aminotransferase, is highly similar to that of the uncharacterized pyridoxal 5ʹ-phosphate (PLP)-dependent amino acid racemase from Pyrococcus horikoshii. The OCC_10945 enzyme was successfully overexpressed in Escherichia coli by coexpression with a chaperone protein. The purified enzyme demonstrated PLP-dependent amino acid racemase activity primarily toward Met and Leu. Although PLP contributed to enzyme stability, it only loosely bound to this enzyme. Enzyme activity was strongly inhibited by several metal ions, including Co2+ and Zn2+, and nonsubstrate amino acids such as l-Arg and l-Lys. These results suggest that the underlying PLP-binding and substrate recognition mechanisms in this enzyme are significantly different from those of the other archaeal and bacterial amino acid racemases. This is the first description of a novel PLP-dependent amino acid racemase with moderate substrate specificity in hyperthermophilic archaea.

Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study.Patients with wild-type KRAS exon 2 mCRC previously treated with fluorouracil-, oxaliplatin- and irinotecan-based chemotherapies were randomised (1:1) to either panitumumab plus irinotecan (panitumumab arm) or cetuximab plus irinotecan (cetuximab arm). The primary end-point was progression-free survival (PFS). The planned sample size was 120, expecting a hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (one-sided alpha error 0.2 and power 0.7). Major secondary end-points were overall survival (OS), response rate and safety.From December 2011 to September 2014, 121 patients were enrolled, and 61 and 59 patients were randomised to the panitumumab and cetuximab arms, respectively (1 patient excluded). Most patients (97%) had received prior chemotherapies containing bevacizumab. The median PFS was 5.42 months in the panitumumab arm and 4.27 months in the cetuximab arm (HR = 0.64, 95% confidence interval [CI] = 0.44-0.94, P 0.001 for non-inferiority, P = 0.058 for superiority), and median OS was 14.85 and 11.53 months (HR = 0.66, 95% CI = 0.44-1.00, P = 0.050 for superiority), respectively. The incidence of grade 3 or 4 hypomagnesaemia was higher in the panitumumab arm than that in the cetuximab arm (17% vs. 7%).Panitumumab may be non-inferior to cetuximab in combination with irinotecan in survival of patients with irinotecan-refractory mCRC.

Metal oxide buffer layers are a promising method for improving the efficiency and stability of organic photovoltaic cells and organic light-emitting diodes. To design organic electronic devices intelligently, it is necessary to understand the electronic structure at organic/metal-oxide interfaces. In this study, the electronic structure of films of a well-known hole-transporting material, N,N′-diphenyl-N,N′-bis(1-naphthyl)-1,1′-biphenyl-4,4′-diamine (α-NPD) on TiOx underlayers was studied via ultraviolet photoemission spectroscopy and inverse photoemission spectroscopy. New electronic states were found near the Fermi level (EF) upon adsorption of α-NPD when the TiOx underlayer was highly oxygen defective. The observed spectra were not fully explained by density functional theory (DFT) calculations for simple ionic α-NPD molecules. In addition, the vacuum level shift at the interfaces was also different from the shift predicted by several theoretical models that do not consider chemical reactions at the interface. These results suggest that the adsorbate–substrate interaction is complicated when a highly defective metal oxide is used. The stoichiometry of the metal oxide buffer layer may have a large effect on carrier injection or extraction properties at the interface.

4518 Background: Transarterial chemoembolization (TACE) with selective catheterization into the segmental or subsegmental hepatic arteries supplying HCC is often performed to achieve the complete local control of HCC in the patients with a limited number of small sized nodules. To clarify which of TACE with drug-eluting beads loaded with epirubicin (DEB-TACE) or conventional TACE with epirubicin-lipiodol (cTACE) can achieve the complete response (CR) more frequently, we performed a randomized controlled trial of DEB-TACE vs. cTACE. Methods: Between March 2016 and May 2019, unresectable HCC patients with Child-Pugh class A or B who were scheduled to receive selective TACE were randomly assigned 1:1 to the DEB-TACE group and the cTACE group. The primary endpoint was the CR rate at 3 months, and the secondary endpoints were the CR rate at 1 month and rate of adverse events (AEs). The response and AEs were assessed according to the modified RECIST by an independent review committee and the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0., respectively. Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE 101 patients) were enrolled from 22 Japanese institutions. The patient characteristics were well-balanced between the two groups. The median number of tumors was one in both groups and the median tumor size was 20.0 mm in the DEB-TACE group and 20.5 mm in the cTACE group. The table shows the CR rates and frequencies of AEs. The CR rates of cTACE at 3 and 1 months were significantly higher than those of DEB-TACE. The frequency of AEs (all grades), including pyrexia, malaise, increased serum total bilirubin (T-Bil) and increased serum alanine transaminase (ALT), was significantly higher in the cTACE group than in the DEB-TACE group. Conclusions: Selective cTACE appeared to have greater efficacy for local tumor control as compared to selective DEB-TACE, however, the frequencies of post-embolization syndromes were higher in the cTACE group than in the DEB-TACE group. Clinical trial information: UMIN000021250 . [Table: see text]

226 Background: The WJOG 6210G trial demonstrated a similar efficacy between FOLFIRI plus Bev and FOLFIRI plus panitumumab (Pani) at 2nd-line treatment in pts with KRAS exon2 wild-type mCRC (Shitara K, et al, Cancer Sci 2016). Recently, angiogenesis biomarker studies of clinical trials have identified VEGF-D as a potential predictor for angiogenesis inhibitors in mCRC. We evaluated whether VEGF-D level are associated with clinical outcomes in the WJOG 6210G trial. Methods: Plasma samples which were collected at pre-treatment were analyzed. VEGF-D level in plasma was measured by means of magnetic bead panel (G & G SCIENCE CO., LTD.). The correlations of VEGF-D level with progression-free survival (PFS) and overall survival (OS) were evaluated by cox regression analyses. Results: Ninety-nine pts were evaluable for VEGF-D level (Bev, n = 51; Pani, n = 48) among 121 pts enrolled in the WJOG6210G. The median VEGF-D level was 441 pg/ml (range 60-1570). VEGF-D level was not affected by the period from last administration of 1st-line Bev to start of 2nd-line treatment. When the median VEGF-D level was adopted as cut-off value, pts with high VEGF-D achieved a shorter PFS and OS than pts with low VEGF-D in the Bev arm [HR: 0.58 (95%CI 0.32-1.07), p = 0.08; HR: 0.62 (95%CI 0.34-1.11), p = 0.10]. In pts with high VEGF-D, the Bev arm tended to have a shorter OS and PFS compared to Pani arm [median: 12.4 m vs. 17.5 m, HR: 1.58 (95%CI 0.87-2.88); median: 4.7 m vs. 5.5 m, HR: 1.31 (95%CI 0.72-2.40)]; whereas, comparable OS and PFS in pts with low VEGF-D [median: 18.9 m vs. 16.5 m, HR: 1.08 (95%CI 0.59-2.01); median: 5.9 m vs. 7.2 m, HR: 1.10 (95%CI 0.62-1.99)]. OS was stratified by VEGF-D level quartile, then OS of Bev arm in each quartile was compared with that of Pani arm (Table). Clinical trial information: UMIN000031621. Conclusions: Our study suggests clinically meaningful association between VEGF-D level and clinical outcomes in mCRC pts treated with 2nd-line FOLFIRI plus Bev. [Table: see text]

Japanese culture values the team approach to leadership, as a team's honor is greater than an individual's honor (Ishikawa, 2012; Turner, 1991). In the 1980s, team spirit gave birth to "Japan No. 1" (White, 1980). Subject to cultural influences, honor and shame are what Japanese samurai often had in mind when they do things. In order to attenuate shame and maintain honor, Japanese samurai performed Seppuku "stomach- or abdomen-cutting" when they brought shame to themselves (Chang, 2015). The researcher believes that such a culture represents a spirit and power controlled by the society within this group, and makes Japanese nationals value teams and groups. Meanwhile, there are also studies that associate samurai spirit with Japanese sports coaches' leadership (Miller, 2011), meaning that leaders in Japanese organizations value a team's honor and develop the concept of samurai paradigms. These thoughts are similar to opinions in Sentocnik and Rupar's (2009) thesis, Future School Leadership, in many ways. Sentocnik and Rupar believed that, in addition with the evolution of value systems in different periods of time, principals' role would march toward a team approach to leadership, diverse leadership, and symboloriented leadership.Taiwan is located at the junction of East Asia and Southeast Asia and is an island country like Japan. Both countries share similar geographic characteristics and a culture rooted in Confucianism (Ling & Shih, 1998; Nosco, 1998). However, Taiwan is an island country with diverse cultures as a result of Dutch, Spanish, and Japanese rule in the past (Li, 2009; Rudolph, 2011). In recent years, transnational marriages are becoming popular in Taiwan with an influx of migrants from the Philippines, Vietnam, Malaysia, Indonesia, and mainland China, which accentuates the phenomenon of cultural diversity in Taiwan. Therefore, more than ever, Taiwan's educational fields in recent years are leaning toward embracing more diverse value systems and complex behaviors (Wu, 2011; Tsai, 2011). Traditional principal-centric leadership behaviors may become unable to handle complex and diverse school environments (Weberg, 2012). Teachers' diverse values and complex behaviors necessitate that a school principal must adopt diverse leadership (multi-frame leadership) (Bolman & Deal, 2008) or compound leadership to cater to different circumstances and conditions (Uhl-Bien, Marion, & McKelvey, 2007).As Taiwan was ruled by Japan, considerable similarities exist between Taiwanese and Japanese culture. However, since Taiwan has not been ruled by Japan for 70 years, Taiwanese culture has diverged from Japanese influence.On the premise that cross-national research of leadership behaviors could enhance the academic value of research results (Boehnke, Bontis, DiStefano, & DiStefano, 2003), this study sets out to explore the similarities and differences of school leadership behaviors in Taiwan and Japan. The benchmark for the comparison of leadership behaviors and the theoretical foundation of leadership behaviors originates from a team approach to instruction leadership, compound leadership (including adaptive leadership and delegative leadership), and diverse leadership (including structureoriented leadership, human resources leadership, politically-oriented leadership, and symbol-oriented leadership), which were emphasized in the thesis, School Leadership in the Future(Sentocnik & Rupar, 2009). This study investigates the aforementioned leadership behaviors and their effects on the basis of two theories: (1) behavioral pattern theory, which argues that leadership behaviors affect subordinate behaviors and organizational performance (Schoner & Kelso, 1988); and (2) behavior theory, which states that leadership behaviors affect subordinate performance (Khan, Nawaz, & Khan, 2016). Premised on these theories, this study examines the differences between these leadership behaviors and developed appropriate indicators for teacher performance and organizational performance. …

We investigated the structural and electronic properties of vacuum sublimed 7,8,15,16-tetraazaterrylene (TAT) thin films on Au(111), Ag(111), and Cu(111) substrates using inverse photoemission spectroscopy, ultraviolet photoelectron spectroscopy (UPS), x-ray photoelectron spectroscopy (XPS), low energy electron diffraction (LEED), and the x-ray standing wave (XSW) technique. The LEED reveals a flat adsorption geometry of the monolayer TAT on these three substrates, which is in accordance with the XSW results. The molecules are slightly distorted in monolayers on all three substrates with the nitrogen atoms having smaller averaged bonding distances than the carbon atoms. On Ag(111) and Cu(111), chemisorption with a net electron transfer from the substrate to the adsorbate takes place, as evidenced by UPS and XPS. Combining these results, we gain full insight into the correlation between electronic properties and interface geometry.

This study examined the microbial transformation of carbazole (CZ) by an isolated bacterium that can use CZ as a sole carbon and nitrogen source. The strain identified as Pseudomonas stutzeri produced a large amount of anthranilic acid (AA) from CZ in the medium containing a nonionic surfactant. In dialysis culture using ion-exchange resin, 7.9 g/liter (58mm) of AA was accumulated from 15g/liter (90mm) of CZ and the molar yield of AA reached about 64%.

Solution-processed perovskite solar cells are attracting increasing interest due to their potential in next-generation hybrid photovoltaic devices. Despite the morphological control over the perovskite films, quantitative information on electronic structures and interface energetics is of paramount importance to the optimal photovoltaic performance. Here, direct and inverse photoemission spectroscopies are used to determine the electronic structures and chemical compositions of various methylammonium lead halide perovskite films (MAPbX3, X = Cl, Br, and I), revealing the strong influence of halide substitution on the electronic properties of perovskite films. Precise control over halide compositions in MAPbX3 films causes the manipulation of the electronic properties, with a qualitatively blue shift along the I → Br → Cl series and showing the increase in ionization potentials from 5.96 to 7.04 eV and the change of transport band gaps in the range from 1.70 to 3.09 eV. The resulting light absorption of MAPbX3 films can cover the entire visible region from 420 to 800 nm. The results presented here provide a quantitative guide for the analysis of perovskite-based solar cell performance and the selection of optimal carrier-extraction materials for photogenerated electrons and holes.

Purpose A multicenter phase I/II study of transarterial chemoembolization with a fine cisplatin powder and gelatin particles (GPs) for multifocal hepatocellular carcinoma (HCC) was conducted. Primary endpoints were dose-limiting toxicity (DLT) and recommended dose (RD). Secondary endpoints were the incidence and severity of adverse events and tumor response. Materials and Methods Nonselective transarterial chemoembolization was performed until all tumor enhancement disappeared. Lipiodol was not used. In the phase I study, the cisplatin dose was escalated from 35 mg/m 2 to 65 mg/m 2 in 15-mg/m 2 increments to determine DLT and RD. In the phase II study, 40 patients were treated with the RD. Toxicity was assessed by Common Toxicity Criteria for Adverse Effects (version 3.0), and tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0) and European Association for the Study of the Liver (EASL) criteria. Results A total of 46 patients were enrolled. As no DLT occurred at any dose level in the phase I study, RD was determined as 65 mg/m 2 . In the phase II study, the treatment was discontinued in one patient as a result of vasovagal response. Toxicities of grade 3 or higher included nausea (2.2%), pancreatitis (2.2%), cholecystitis (2.2%), thrombocytopenia (8.7%), hyperbilirubinemia (2.2%), and increased aspartate aminotransferase (28.3%) and alanine aminotransferase (21.7%) levels. Tumor response rates under RD were 25.6% and 64.1% by RECIST and EASL criteria, respectively. Conclusions Nonselective transarterial chemoembolization with fine cisplatin powder and GPs was well tolerated and effective in patients with multifocal HCC at the RD of 65 mg/m 2 .

In recent years, there has been an increase in deviant behaviors of students in Japan and Taiwan. The similarities and differences between the deviant behaviors of students in these 2 countries were investigated. A total of 516 and 476 valid questionnaires were obtained from Taiwan and Japan, respectively, in this study. Results indicated that there were fewer deviant behaviors among students in Taiwan than in Japan. Social control, authoritative teacher discipline, and parents' laissez-faire parenting were common factors implicated in deviant behaviors of students in both countries. The factor most frequently affecting the deviant behaviors of Japanese students was social control. For Taiwanese students authoritative teacher discipline was the factor with the greatest effect.

A phase II study of stent therapy for unresectable malignant colorectal obstruction was conducted to ascertain the clinical efficacy, safety, and procedural feasibility.Inclusion criteria comprised unresectable obstruction of the rectum or sigmoid colon; no other apparent stenosis; performance status by Eastern Cooperative Oncology Group ≤3; and maintained major organ function. The treatment protocol was to place an uncovered metal stent through the anus in an obstructive portion under x-ray fluoroscopic guidance. The patients were followed for 4 weeks after therapy, and the degree of improvement in subjective symptoms lasting ≥2 weeks was assessed as effective when the patient was decompressed with stent, or ineffective when not decompressed. Rate of clinical efficacy was defined as the proportion of effective cases.The participants of the study comprised 33 patients (13 men and 20 women; mean age, 60 y). Rate of procedure completion was 97.0% (32/33). Treatment was effective in 27 patients, ineffective in 4, and unassessable in 1, yielding a clinical efficacy rate of 81.8% (27/33). Death owing to underlying disease (n=3), stent removal owing to anal pain (n=1), and occlusion at another location (n=1) were noted. No recurrences were seen among clinically effective cases. Adverse reactions included grades 2 to 3 diarrhea (n=12), pain (n=5), bleeding (n=1), and dysuria (n=1), but no grade 4 adverse reactions or treatment-related deaths were identified.Stent therapy for unresectable malignant colorectal obstruction is effective, safe, and feasible.

Oligothiophene derivatives, 4,4’-bis-(2-aminoethylthienyl)-3,4-ethylenedioxythiophene dihydrohalide (AET-EDOT·HX: X = I, Br), were synthesized by Grignard coupling reactions. The hybrid films of oligothiophene and lead halide were fabricated by casting and spin-coating methods. The effect of halogen species on the optical properties of the perovskites was investigated. The X-ray diffraction profiles of (AET-EDOT)PbX4 cast films indicated that the layered structures were formed by the self-organization. After hybridization of AET-EDOT·HX with PbX2, new absorption peaks due to the confined excitons were observed at 400 nm for (AET-EDOT)PbBr4 film, and at 395 nm for (AET-EDOT)PbI4 film. These results indicated that the diamino-type oligothiophenes were successfully incorporated into the organic-inorganic layered perovskites. AFM images of (AET-EDOT)PbX4 cast films showed polycrystalline grains, indicating that the polycrystalline structures covered on the substrate surface.

Optical properties in a single crystal of the organic-inorganic hybrid perovskite quantum-well material (C4H9NH3)2(CH3NH3)Pb2Br7 have been investigated. This material has double-layer sheets of corner-sharing [PbBr6]4- octahedrons constituting the inorganic well. The estimated longitudinal-transverse (LT) splitting, exciton exchange energy, and biexciton binding energy are about 60 meV, 17 meV and 26 meV respectively. We can also study well-width dependence in angstroms by comparing with (C4H9NH3)2PbBr4 which has single-layer sheets comprising the inorganic well. This is the first time the well-width dependence of excitonic properties in hybrid organic-inorganic quantum materials is investigated. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

750 Background: The alternate-days administration of S-1 was suggested to reduce toxicities such as GI-related adverse events (AEs) or neutropenia maintaining efficacy in some previous reports. This phase II study was aimed to evaluate an alternate-day administration of S-1 combined with bevacizumab in untreated elderly patients with mCRC. Methods: The key eligibility criteria included age ≥75 years, first-line chemotherapy, measurable lesions, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, preserved organ function, and refusal of oxaliplatin- or irinotecan-containing regimen as the initial chemotherapy. Patients received 40 mg (body surface area [BSA] ≤1.25 m2), 50 mg (BSA > 1.25 to ≤1.50 m2), or (BSA > 1.50 m2) of S-1 orally, twice a day, on Monday, Wednesday, Friday, and Sunday every week. Bevacizumab of 7.5 mg/kg was administered every 3 weeks. Primary endpoint was progression-free survival (PFS). Expected median PFS was 8.5 months, and efficacy threshold was 5.0 months. The required sample size was calculated as 50 patients, with a 2-sided type I error of 10% and a power of 80%. Results: Of 54 enrolled patients, 50 patients for efficacy and 53 patients for safety were evaluated. The median age was 79 years (range, 75–88), and 56% had an ECOG PS of 0. The median follow-up time was 34.5 months (95% confidence interval [CI], 25.6–44.9). Median PFS was 8.1 months (95%CI, 7.4–10.1). Median overall survival was 22.8 months (95%CI, 16.9–28.5). The response rate and disease control rate were 44% and 88%, respectively. Grade 3 or more hematologic, non-hematologic, and bevacizumab-related AEs were observed in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Treatment-related death caused by cerebral infarction was observed in one patient. Conclusions: The primary endpoint was met. The alternate-days administration of S-1 combined with bevacizumab was well tolerated and effective in elderly patients with mCRC. Clinical trial information: UMIN000010402.

A diglycidyl ether of bisphenol A was crosslinked with several acid anhydrides of different structures, such as the homologs of succinic anhydride and the acid anhydrides with a double bond or a ring structure. Dilatometric, dielectric, and dynamic mechanical measurements were carried out on the cured resins. The glass transition temperature is shown to be influenced by the presence of double bonds or ring structures in the chain backbones. The specific volume at the glass transition temperature can be predicted as a sum of atomic volumes. Two dielectric relaxation processes were observed in all the resins. The temperature dependence of the relaxation time for the α-process can be represented by the WLF equation. The mechanical retardation time for the α-process generally agrees with the dielectric relaxation time. The observed dynamic Young's modulus in the glassy state is nearly one-third of the value calculated from the cohesive heat density. A good correspondence is obtained between the observed dynamic Young's modulus in the rubbery state and the Young's modulus calculated from the crosslinking density, but the deviation increases with decreasing crosslinking density.

Background We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. Patients and Methods The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m2/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. Results Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. Conclusion UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.

In this paper we describe the conceptual design and cooling blade development of a 1700°C-class high-temperature gas turbine in the ACRO-GT-2000 (Advanced Carbon Dioxide Recovery System of Closed-Cycle Gas Turbine Aiming 2000 K) project. In the ACRO-GT closed cycle power plant system, the thermal efficiency aimed at is more than 60% of the higher heating value of fuel (HHV). Because of the high thermal efficiency requirement, the 1700°C-class high-temperature gas turbine must be designed with the minimum amount of cooling and seal steam consumption. The hybrid cooling scheme, which is a combination of closed loop internal cooling and film ejection cooling, was chosen from among several cooling schemes. The elemental experiments and numerical studies, such as those on blade surface heat transfer, internal cooling channel heat transfer, and pressure loss and rotor coolant passage distribution flow phenomena, were conducted and the results were applied to the conceptual design advancement. As a result, the cooling steam consumption in the first stage nozzle and blade was reduced by about 40% compared with the previous design that was performed in the WE-NET (World Energy Network) Phase-I.

Previous work has elucidated that the wall slip velocity and viscosity of polymer melts influence the thickness uniformity of blown film. The present study investigates the effects of the stress dependence of wall slip, the shear thinning and the density on the uniformity. We have prepared high-density polyethylenes with a variety of molecular weight distributions, which have different rheological properties. Examination of the thickness uniformity of their blown film has shown that the uniformity is correlated with wall slip velocity, the stress dependence of the velocity, melt viscosity, shear thinning and density; the coefficient of the correlation is determined to be 0.990. The reason why the stress dependence of wall slip and the shear thinning affect the uniformity is explained in terms of polymer melt flow behavior in a die, while the effect of density is interpreted considering bubble fluctuation in the blow-up process. Polym. Eng. Sci. 44:965–972, 2004. © 2004 Society of Plastics Engineers.

One of the most important materials for blown film is high-density polyethylene (HDPE) with wide molecular weight distribution. First, we computed a wall stress at the entrance of a spiral groove in a particular die during blown film processing on a particular condition, to which a similar condition is widely utilized in a film works. The computed value is about 170 kPa, while the HDPE melt slips at die wall at stresses above approximately 50 kPa. The stress of 170 kPa is sufficiently large for the slip occurrence of the melt. Then, we investigated the effects of wall slip and melt viscosity on film thickness distribution in the circumferential direction: the distribution tends to decrease with decreasing wall slip and melt viscosity. This tendency is explained by considering flow distribution in a spiral mandrel die and polymer melt flow characteristics.

The development of integrated coal gasification combined cycle (IGCC) systems ensures higher thermal efficiency and environmentally sound options for supplying future coal utilizing power generation needs. The Japanese government and electric power industries in Japan promoted research and development of an IGCC system using an air-blown entrained-flow coal gasifier. On the other hand, Europe and the United States are now developing the oxygen-blown IGCC demonstration plants. Gasified coal fuel produced in an oxygen-blown entrained-flow coal gasifier, has a calorific value of 8–13 MJ/m3 which is only 1/5–1/3 that of natural gas. However, the flame temperature of medium-Btu gasified coal fuel is higher than that of natural gas and so NOx production from nitrogen fixation is expected to increase significantly. In the oxygen-blown IGCC, a surplus nitrogen produced in the air-separation unit (ASU) is premixed with gasified coal fuel (medium-Btu fuel) and injected into the combustor, to reduce thermal-NOx production and to recover the power used for the ASU. In this case, the power to compress nitrogen increases. Low NOx emission technology which is capable of decreasing the power to compress nitrogen is a significant advance in gas turbine development with an oxygen-blown IGCC system. Analyses confirmed that the thermal efficiency of the plant improved by approximately 0.3% (absolute) by means of nitrogen direct injection into the combustor, compared with a case where nitrogen is premixed with gasified coal fuel before injection into the combustor. In this study, based on the fundamental test results using a small diffusion burner and a model combustor, we designed the combustor in which the nitrogen injection nozzles arranged on the burner were combined with the lean combustion technique for low-NOx emission. In this way, we could reduce the high-temperature region, where originated the thermal-NOx production, near the burner positively. And then, a combustor with a swirling nitrogen injection function used for a gas turbine, was designed and constructed, and its performance was evaluated under pressurized conditions of actual operations using a simulated gasified coal fuel. From the combustion test results, the thermal-NOx emission decreased under 11 ppm (corrected at 16% O2 ), combustion efficiency was higher than 99.9% at any gas turbine load. Moreover, there was different effects of pressure on thermal-NOx emission in medium-Btu fuel fired combustor from the case of a natural gas fired combustor.

We have investigated how a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects thyroid hormone regulation, especially in relation to the localization of thyroid stimulating hormone (TSH) in the pituitary and that of thyroxin (T4) of the thyroid in the rat. Female Sprague-Dawley rats were given a single oral administration of TCDD ranging from 1.0 to 4.0 microg/kg body weight (bw), and then tissue specimens were removed on day 7 post-administration. Thyroid hormone concentrations were measured in serum, and the expression of the TCDD-responsive genes, UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P4501A1 (CYP1A1) were examined in the liver. TCDD administration resulted in an increase in both immunostaining intensity and the number of TSH-positive cells in the anterior pituitary. T4 was found to localize only in the follicular lumen of the thyroid in vehicle-treated control rats, while TCDD administration caused a foamy change in the colloid of some follicles, an indication of accelerating the biosynthesis of T4 in the thyroid. By morphometrical analysis, the ratio of parenchymal/lumenal area of the thyroid was found to increase in response to TCDD. TCDD treatment as low as 2.0 microg TCDD/kg bw induced a significant decrease in both serum total T4 (TT4) and free T4 (FT4) concentrations in the rats, with a significant increase in serum TSH levels in the 4.0 microg TCDD/kg bw rats. Serum total triiodothyronine (TT3) level was unchanged in all groups. The UGT1 gene was significantly induced at a TCDD dose as low as 1.0 microg/kg bw in a dose-dependent manner. TCDD concentrations in the serum, liver and adipose tissues were detected in a dose-related fashion. The present immunohistochemical results clearly support the earlier biochemical findings on the perturbation of the thyroid-pituitary axis by TCDD and suggest that UGT1 is an immediate target of a low TCDD exposure that triggers the perturbation.

Advanced cancer patients with good performance status (PS) sometimes show poor prognosis despite receiving some chemotherapies. We evaluated prognosis of chemo-naive advanced biliary tract cancer (ABTC) patients with good PS by Glasgow Prognostic Score (GPS). Sixty-two patients with Eastern Cooperative Oncology Group PS 0 or 1 were retro- spectively analyzed, using multivariate Cox regression. GPS was defined with serum levels of two parameters, albumin(3.5 g/dl and C-reactive protein \1.0 mg/dl (both as 0, either as 1, and neither as 2). PS 0 (n = 32) and 1 (n = 30) patients had similar survival (P = 0.98). The median overall survival (OS) was 17.0 months for GPS 0 (n = 19), 14.2 months for GPS 1 (n = 17), and 6.4 months for GPS 2 (n = 26). GPS 2 had sig- nificantly shorter OS than GPS 0 (P = 0.002) or 1 (P = 0.033). Multivariate analysis identified two independent prognostic factors: GPS (hazard ratio 0.60, 95 % confidence interval 0.40-0.90, P = 0.012) and liver metastasis (hazard ratio 0.43, 95 % CI 0.20-0.90, P = 0.026). GPS was useful for chemo- naive ABTC patients with good PS.

The development of integrated, coal-gasification combined cycle (IGCC) systems provides cost-effective and environmentally sound options for meeting future coal-utilizing power generation needs in the world. The Japanese government and the Electric Power Industries in Japan promoted research and development of an IGCC system. We have being working on developing a low-NOx combustion technology used in gas turbine combustors for IGCC. Each gaseous fuel produced from some raw materials contained CO and H2 as the main combustible components, and a small amount of CH4. Compositions and calorific values of gasified coal fuels varied widely depending on raw materials and gasifier types. Gaseous fuel, produced in various gasifiers, has a calorific value of 4–13MJ/m 3, which is about one-tenth to one-third that of natural gas. The flame temperatures of fuels increase as the fuel calorific value rises. When the fuel calorific value rises 8MJ/m 3 or higher, the flame temperature is higher than that of natural gas, and so NOx production from nitrogen fixation is expected to increase significantly. Also, some gasified coal fuels contain fuel nitrogen, such as ammonia, if the hot/dry type gas cleaning system is employed. These factors affect the combustion characteristics of the gasified coal fuel. In this paper, we clarified the influence of gasified coal fuel properties on NOx and CO emissions through experiments using a small diffusion burner and through numerical analysis based on reaction kinetics. The main results were as follows: (1) NH3 conversion to NOx increases with increasing CH4 concentration in gaseous fuel. (2) If gaseous fuel contains CH4, there will be some specific equivalence ratio in the primary combustion zone for the minimum NH3 conversion to NOx in the two-staged combustion. (3) Its specific equivalence ratio in the primary combustion zone increases with decreasing CH4 concentration in gaseous fuel. (4) If the fuel contains a small percent of CH4, there is no influence of the CO/H2 molar ratio in the fuel on the conversion rate of NH3 to NOx, while there is an influence in the case where fuel contains no CH4. The conversion rate increases with rises in the CO/H2 molar ratio. (5) As the pressure increases, the conversion rate of NH3 to NOx slightly decreases and the CO emission declines significantly.

A catalytically assisted low NOx combustor has been developed which has the advantage of catalyst durability. This combustor is composed of a burner section and a premixed combustion section behind the burner section. The burner system consists of six catalytic combustor segments and six premixing nozzles, which are arranged alternately and in parallel. Fuel flow rate for the catalysts and the premixing nozzles are controlled independently. The catalytic combustion temperature is maintained under 1000°C, additional premixed gas is injected from the premixing nozzles into the catalytic combustion gas, and lean premixed combustion at 1300°C is carried out in the premixed combustion section. This system was designed to avoid catalytic deactivation at high temperature and thermal or mechanical shock fracture of the honeycomb monolith. In order to maintain the catalyst temperature under 1000°C, the combustion characteristics of catalysts at high pressure were investigated using a bench scale reactor and an improved catalyst was selected for the combustor test. A combustor for a 20 MW class multi-can type gas turbine was designed and tested under high pressure conditions using LNG fuel. Measurements of NOx, CO and unburned hydrocarbon were made and other measurements were made to evaluate combustor performance under various combustion temperatures and pressures. As a result of the tests, it was proved that NOx emission was lower than 10 ppm converted at 16% O2, combustion efficiency was almost 100% at 1300°C of combustor outlet temperature and 13.5 ata of combustor inlet pressure.

In integrated coal gasification combined-cycle power-generation (IGCC) systems, ammonia in gasified fuel is passed through a hot/dry type gas clean-up facility into a gas turbine. The ammonia is converted to nitrogen oxides in the gas turbine combustion process. Therefore, ammonia removal from coal-gasified fuel effectively reduces NO{sub x} emissions in IGCC systems. The authors clarified the optimum NO/NH{sub 3} ratio, the optimum concentration of added O{sub 2}, and the influence of CO, H{sub 2}, and CH{sub 4} in the coal-gasified fuel on NH{sub 3} decomposition and NO reduction through experiments using a tubular flow reactor and numerical analysis based on reaction kinetics. The main results were as follows: (1) The optimum NO/NH{sub 3} ratio for maximizing NH{sub 3} decomposition and NO reduction was about 1. (2) The NH{sub 3} decomposition ratio depended only on H{sub 2}, and decreased rapidly with increasing H{sub 2} concentration. (3) The NO reduction ratio decreased with an increasing H{sub 2} concentration. (4) The remaining CH{sub 4}, which was not decomposed by pyrolysis, increased with an increasing CH{sub 4} concentration and caused the reaction temperature to rise, as opposed to cases of CO and H{sub 2}. (5) The method was effective in decreasing total fixed nitrogenmore » (TFN) by up to 40% and minimizing the total concentration of remaining NH{sub 3} and NO in air-blown, coal-gasified fuel.« less

Recently, use of gas turbine systems such as combined cycle and cogeneration systems has gradually increased in the world. But even when a clean fuel such as LNG (liquefied natural gas) is used, thermal NOx is generated in the high temperature gas turbine combustion process. The NOx emission from gas turbines is controlled through selective catalytic reduction processes (SCR) in the Japanese electric industry. If catalytic combustion could be applied to the combustor of the gas turbine, it is expected to lower NOx emission more economically. Under such high temperature and high pressure conditions as in the gas turbine, however, the durability of the catalyst is still insufficient. So it prevents the realization of a high temperature catalytic combustor. To overcome this difficulty, a catalytic combustor combined with premixed combustion for a 1300°C class gas turbine was developed. In this method, catalyst temperature is kept below 1000°C and a lean premixed gas is injected into the catalytic combustion gas. As a result, the load on the catalyst is reduced and it is possible to prevent the catalyst deactivation. After a preliminary atmospheric test, the design of the combustor was modified and a high pressure combustion test was conducted. As a result, it was confirmed that NOx emission was below 10ppm (at 16% O2) at a combustor outlet gas temperature of 1300°C and that the combustion efficiency was almost 100%. This paper presents the design features and test results of the combustor.

Ammonia contained in coal-gasified fuel is converted to nitrogen oxides (NO{sub x}) in the combustion process of a gas turbine in integrated coal gasification combined cycle (IGCC) system. Research data on fuel-NO{sub x} formation are insufficient, and there still remains a wide explored domain. The present research aims at obtaining fundamental knowledge of fuel-NO{sub x} formation characteristics by applying reaction kinetics to gas turbine conditions. An instantaneous mixing condition was assumed in the cross section of a gas turbine combustor and both gradual mixing condition and instantaneous mixing condition were assumed at secondary air inlet section. The results may be summarized as follows: (1) in the primary combustion zone under fuel rich condition, HCN and other intermediate products are formed as ammonia contained in the fuel decomposes; (2) formation characteristics of fuel-NO{sub x} are affected by the condition of secondary air mixing; and (3) the conversion ratio from ammonia to NO{sub x} declines as the pressure inside the combustor rises under the condition of gradual mixing at the secondary air inlet. These results obtained agreed approximately with the experimentation.

Developing integrated coal gasification combined cycle (IGCC) systems ensures cost-effective and environmentally sound options for supplying future power generation needs. In order to enhance thermal efficiency of IGCC and to reduce NOx emission, a 1500°C-class gas turbine combustor for IGCC was designed, tested, and the performance of the combustor was evaluated under pressurized conditions. The designed combustor had the following three characteristics: (1) in order to assure the stable combustion burning low-Btu gas (LBG), an auxiliary combustion chamber was installed at the entrance of the combustor; (2) to reduce fuel NOx emission that was produced from the ammonia (NH3) in the fuel, the rich-lean combustion method was introduced; and (3) to compensate for the declined cooling-air associated with the higher temperature of the gas turbine, the tested combustor was equipped with a dual-structure transition piece so that the cooling air in the transition piece can be recycled to cool down the combustor liner wall. As a result of combustor tests, it is confirmed that CO emission is less than 20 ppm, the conversion rate of NH3 which contains about 1000 ppm in the coal gasified fuel to NOx shows 40 percent or below, and the liner wall temperature remained below almost 850°C under high pressure (1.4 MPa), rated load condition.

Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation.

Import of apple fruit from Korea amounted to about 50 to 60 metric tons in '92 to '94. Main cultivar in Korea and Japan is 'Fuji' for its sweetness and adequate hardness of the fruit. So, it is very important to compare the quality of the fruit between Japan and Korea for the future of apple trading. We collected six carton boxes in which medium-sized fruits (32-40 fruits/box) apiece from Yochon and Taegu in Korea, and two carton boxes each from Aomori, Akita, Yamagata, Fukushima and Nagano (Nagano city and Matsukawa town) in Japan, and analyzed the fruit weight, shape, hardness, Brix, titratable acid and rate of squeeze. We had measured temperature and precipitation of the districts in fruit growth period and analyzed the influence of climatic conditions to the quality of the fruit. Mean and maximum temperature in July of Taegu and yochon, Korea were higher than Japan, and minimum temperature during June to October of Aomori was lower than other districts of both countries. Precipitation of Matsukawa during May to September was heavier than other districts of both countries, however precipitation was almost same in all districts of both countries except Matsukawa. Fruits weight of Fukushima was largest and of other districts was almost same, and difference of diameter and length of Japanese fruits were smaller than Korea. So, the fruits of Japan were more symmetric than Korean ones. However, the deference of D/L index, flesh hardness, Brix, titratable acid and rate of squeeze was not significant between Japan and Korea. Coefficient of variation (C.V.) of fruit weight, diameter, length and D/L index in Japan were remarkably smaller than Korea, however, the fresh hardness, Brix, titratable acid and rate of squeeze were not so different between Japan and Korea.

Numerical computations are made of laminar jet diffusion flames taking into account detailed chemical kinetics and multicomponent diffusion and focusing on the effect of pressure and the amounts of hydrocarbon contained in the fuel on the NOx formation processes and charcteristics. In order to clearly distinguish between thermal NOx and fuel NOx originating from N2 in the air and fuel N, respectively, and to elucidate the effects of interaction between thermal Nox and fuel Nox together with N-containing species, N-containing species originating from N2 in air and fuel N and their reactions are distinguished in the computations. It was shown that(1)higher pressure results in a decrease in the amount of fuel NO formed and a increase in the amount of thermal NO formed, (2)the tendency of the decrease of the conversion rate of ammonia to fuel NO for high-pressure flames becomes more apparent when the fuel contains greater amounts of methane, (3)the effect of the destruction of thermal NO by N-containing species becomes more apparent for high-pressure flames as thermal NO concentration becomes high.

The magnetic chromatography of magnetic fine particles has been proposed using a periodically intermittent magnetic field. A separation column packed with magnetically permeable steel beads is inserted into the center hole of an electromagnetic coil. The steel beads are coated with a polytetrafluoroethylene film, and the column is vibrated atca. 10Hz in order to minimize any irreversible adsorption of the magnetic particles on the beads. Ethanol is used as a mobile phase, and the iron oxide magnetic particles in the mobile phase are continuously monitored by flame atomic absorption spectroscopy. An elution peak for magnetite particles is delayed with increasing coil current and loading ratio of the magnetic field, while that for hematite particles is not influenced by the magnetic field. The effects of various parameters on the retention time for the magnetite particles are discussed from a theoretical viewpoint.

Geophysical and geological surveys of the western part of the Wilkes Land margin were conducted in the 1994-95 austral summer season. The survey area covers the continental slope and rise as well as Bruce Rise in the western end of the margin. Sediments above the basement in the survey area are divided into six sequences. The continent-ocean boundary (COB) occurs at about 64°S, and total thickness of sediments exceeds 5 s in two-way time around the COB in the eastern part of the survey area. Bottom simulating reflectors are frequently observed in the continental slope area. A conspicuous unconformity is observed in Bruce Rise. The basement almost crops out near the northern and eastern ends of the rise, and the sequences below the unconformity dip west to southwest.