Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial.

BACKGROUND: Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. METHODS: We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m2 on days 1 and 8 and fluorouracil 330 mg/m2 continuously on days 1-5 and 8-12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. FINDINGS: Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1-14·5] vs 11·5 months [8·2-14·8]; hazard ratio 1·009 [95% CI 0·743-1·371]; p=0·955). Grade 3-4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). INTERPRETATION: Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. FUNDING: Japanese Ministry of Health, Labour and Welfare.

A multi-center prospective study randomizing the use of fat emulsion in intensive glucose control after allogeneic hematopoietic stem cell transplantation using a myeloablative conditioning regimen.

BACKGROUND & AIMS: Although parenteral nutrition (PN) is often used after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there is controversy regarding PN management, for instance in the use of fat emulsion and glucose control (GC). To clarify these issues, we conducted a multi-center prospective study with intensive GC, randomizing the use of fat emulsion after allo-HSCT using a myeloablative conditioning regimen. METHODS: The primary endpoint was the cumulative incidence of documented infectious disease, namely bacterial and fungal infection, at day 100 after allo-HSCT. Between August 2007 and March 2012, we enrolled 81 patients at 5 centers. Excluding 5 ineligible patients, 76 patients received the protocol treatment. The target fasting glucose level was 80-110 mg/dL. RESULTS: The median follow-up of surviving patients was 1796 days. The cumulative incidences of documented infectious disease at day 100 were 16% (95% confidence interval [CI] 6-29%) in the no-fat group and 19% (95% CI 8-32%) in the fat group, indicating no significant difference. The mean glucose level at 28 days after allo-HSCT was 107 mg/dL in the no-fat group and 111 mg/dL in the fat group. Grade 3 hyperglycemia (>250 mg/dL) and grade 3 hypoglycemia (<40 mg/dL) occurred in 4 patients each (5.3%). Overall survival and non-relapse mortality rates at 4 years were 75% and 11% in the no-fat group and 69% and 8% in the fat group, respectively. CONCLUSIONS: Irrespective of the use of fat emulsion, the long-term clinical outcomes of the enrolled patients were favorable under intensive GC. To further clarify the benefits of GC after allo-HSCT, a prospective study randomizing the level of GC is warranted.

Highly efficient narrow-band green and red phosphors enabling wider color-gamut LED backlight for more brilliant displays.

In this contribution, we propose to combine both narrow-band green (ß-sialon:Eu(2+)) and red (K(2)SiF(6):Mn(4+)) phosphors with a blue InGaN chip to achieve white light-emitting diodes (wLEDs) with a large color gamut and a high efficiency for use as the liquid crystal display (LCD) backlighting. ß-sialon:Eu(2+), prepared by a gas-pressure sinteing technique, has a peak emission at 535 nm, a full width at half maximum (FWHM) of 54 nm, and an external quantum efficiency of 54.0% under the 450 nm excitation. K(2)SiF(6):Mn(4+) was synthesized by a twe-step co-precipitation methods, and exhibits a sharp line emission spectrum with the most intensified peak at 631 nm, a FWHM of ~3 nm, and an external quantum efficiency of 54.5%. The prepared three-band wLEDs have a high color temperature of 11,184 - 13,769 K (i.e., 7,828 - 8,611 K for LCD displays), and a luminous efficacy of 91 - 96 lm/W, measured under an applied current of 120 mA. The color gamut defined in the CIE 1931 and CIE 1976 color spaces are 85.5 - 85.9% and 94.3 - 96.2% of the NTSC stanadard, respectively. These optical properties are better than those phosphor-cpnverted wLED backlights using wide-band green or red phosphoprs, suggesting that the two narrow-band phosphors investigated are the most suitable luminescent materials for achieving more bright and vivid displays.

Phase II study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage II-III esophageal carcinoma.

OBJECTIVE: Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. We evaluated the efficacy and toxicity of radiotherapy at a dose of 50.4 Gy concurrent with chemotherapy for Stage II-III esophageal cancer. METHODS: Esophageal cancer patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) were eligible. Radiotherapy was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Concurrent chemotherapy comprised two courses of 5-fluorouracil (1000 mg/m(2)/day) on days 1-4 and 2-h infusion of cisplatin (75 mg/m(2)) on Day 1; this was repeated every 4 weeks. Two courses of 5-fluorouracil with cisplatin were added. RESULTS: Fifty-one patients were enrolled in the study from June 2006 to May 2008. The characteristics of the 51 patients enrolled were as follows: median age 64 years; male/female, 45/6; performance status 0/1, 32/19 patients; Stage IIA/IIB/III, 9/20/22 patients, respectively. A complete response was achieved in 36 patients (70.6%). The 1- and 3-year overall survival rate was 88.2 and 63.8%, respectively. The median 1- and 3-year progression-free survival rate was 66.7% (80% CI: 57-74%) and 56.6% (80% CI: 47.1-64.9%), respectively. Acute toxicities included Grade 3/4 anorexia (45%), esophagitis (35%) and febrile neutropenia (20%). Eight patients (15.6%) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery. CONCLUSION: Chemoradiation therapy at a dose of 50.4 Gy with elective nodal irradiation is promising with a manageable tolerability profile in esophageal cancer patients.

On the origin of fine structure in the photoluminescence spectra of the ß-sialon:Eu2+ green phosphor.

The photoluminescence (PL) and PL excitation (PLE) spectra of Si6-z Al z O z N8-z (ß-sialon):Eu2+ phosphors with small z values (z=0.025-0.24) were studied at room temperature and 6 K. The PL and PLE spectra exhibit fine structure with the PL lines being as sharp as 45-55 nm even at room temperature; this fine structure was enhanced by decreasing the z value. These results can be used for expanding the color gamut of liquid crystal displays, particularly in the blue-green region. From low-temperature measurements, the fine PLE structure was ascribed to discrete energy levels of 7FJ states. The 4f65d excited states of Eu2+ are considered to be localized near the 4f orbital. This is because the bonding of Eu2+ with surrounding atoms is ionic rather than covalent. Lattice phonon absorptions were also observed in the PLE spectrum, revealing that the optically active Eu2+ ions are located in the ß-sialon crystal. The PL spectrum of the sample with the smallest z value (0.025) consists of a sharp zero-phonon line and lattice phonon replicas, which results in a sharp and asymmetric spectral shape.

Oxaliplatin-free interval as a risk factor for hypersensitivity reaction among colorectal cancer patients treated with FOLFOX.

BACKGROUND: Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood. PATIENTS AND METHODS: Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed. RESULTS: Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016). CONCLUSIONS: An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.

Convergence of leaf display and photosynthetic characteristics of understory Abies amabilis and Tsuga heterophylla in an old-growth forest in southwestern Washington State, USA.

We compared the morphological and physiological characteristics of understory trees of Abies amabilis (Dougl. ex Loud.) Dougl. ex J. Forbes and Tsuga heterophylla (Raf.) Sarg. growing adjacent to each other in an old-growth forest in southwestern Washington State, USA. We hypothesized that, despite contrasting branching patterns and crown architectures, the two species should exhibit convergence in leaf display and photosynthetic gain per light intercepting area, because these are important properties determining their survival in the light-limited understory. The branching pattern of A. amabilis was regular (normal shoot-length distribution, less variable branching angle and bifurcation ratio), whereas that of T. heterophylla was more plastic (positively skewed shoot-length distribution, more variable branching angle and bifurcation ratio). The two species had similar shoot morphologies: number of leaves per unit shoot length and leaf to axis dry mass ratio. Leaf morphology, in contrast, was significantly different. Leaves of A. amabilis were larger and heavier than those of T. heterophylla, which resulted in lower mass-based photosynthetic rate for A. amabilis. Despite these differences, the two species had similar levels of leaf overlap and area-based photosynthetic characteristics. Needle longevity of A. amabilis was nearly twice that of T. heterophylla. The leaf N contents of current and 1-year-old leaves were lower for A. amabilis than for T. heterophylla. However, the leaf N content of A. amabilis did not change from current leaves to 6-year-old leaves, whereas that of T. heterophylla decreased with increasing leaf age. Abies amabilis had deeper crowns than T. heterophylla and retained branches with low relative growth rates. Longer branch retention may compensate for the lower branch-level assimilation rate of A. amabilis. We inferred that the convergence of leaf display and photosynthetic characteristics between A. amabilis and T. heterophylla may contribute to the persistence of both species in the understory of this forest.

Possible association between obesity and posttransplantation complications including infectious diseases and acute graft-versus-host disease.

Both obesity and malnutrition are considered risk factors for complications after bone marrow transplantation (BMT). To elucidate the impact of pretransplantation body mass index (BMI) on clinical outcome, we performed a retrospective cohort study with registration data from the Japan Marrow Donor Program (JMDP). Between January 1998 and December 2005, a total of 3935 patients received unrelated BMT through the JMDP; of these, 3827 patients for whom pretransplantation height and weight data were available were included in the study. Patients were stratified according to pretransplantation BMI values (low BMI: BMI < 18 kg/m(2), n = 295; normal BMI: 18 < or = BMI < 25 kg/m(2), n = 2906; overweight: 25 < or = BMI <30 kg/m(2), n = 565; obese: 30 kg/m(2) < or = BMI, n = 61). In a univariate analysis, pretransplantation BMI was associated with a significantly greater risk of grade II-IV acute graft-versus-host disease (GVHD; P = .03). Multivariate analysis showed that pretransplantation BMI tended to be associated with an increased risk of grade II-IV acute GVHD (P = .07). Obesity was associated with an increased risk of infection compared with normal BMI (odds ratio = 1.9; 95% confidence interval = 1.1 to 3.2; P = .02). Our findings demonstrate a correlation between pretransplantation BMI and posttransplantation complications. Although BMI depends strongly on multiple factors, the effect of obesity on clinical outcome should be evaluated in a prospective study.