High incidence of disseminated intravascular coagulation and acute cerebral infarction in acute myeloid leukemia with cup-like nuclei.

In this study, we examined a cohort of Japanese patients with acute myeloid leukemia (AML) with cup-like nuclei. In particular, we attempted to provide a detailed definition of the clinical features of AML with cup-like nuclei. The clinical records of patients diagnosed with de novo AML were collected retrospectively. We showed that approximately 23% of all patients with AML diagnosed during the study period had AML with cup-like nuclei. All three cup-like AML cases had FLT3-ITD mutations. In addition, we reported a high incidence of disseminated intravascular coagulation and acute cerebral infarction in patients with AML with cup-like nuclei. Our results show that AML with cup-like nuclei may be more common than expected. Due to these unique characteristics, recognition of this morphology is recommended.

Exploring Biomolecular Self-Assembly with Far-Infrared Radiation.

Physical engineering technology using far-infrared radiation has been gathering attention in chemical, biological, and material research fields. In particular, the high-power radiation at the terahertz region can give remarkable effects on biological materials distinct from a simple thermal treatment. Self-assembly of biological molecules such as amyloid proteins and cellulose fiber plays various roles in medical and biomaterials fields. A common characteristic of those biomolecular aggregates is a sheet-like fibrous structure that is rigid and insoluble in water, and it is often hard to manipulate the stacking conformation without heating, organic solvents, or chemical reagents. We discovered that those fibrous formats can be conformationally regulated by means of intense far-infrared radiations from a free-electron laser and gyrotron. In this review, we would like to show the latest and the past studies on the effects of far-infrared radiation on the fibrous biomaterials and to suggest the potential use of the far-infrared radiation for regulation of the biomolecular self-assembly.

Optimum excitation wavelength and photon energy threshold for spintronic terahertz emission from Fe/Pt bilayer.

Terahertz emission from ferromagnetic/non-magnetic spintronic heterostructures had been demonstrated as pump wavelength-independent. We report, however, the pump wavelength dependence of terahertz emission from an optimized Fe/Pt spintronic bilayer on MgO substrate. Maximum terahertz generation per total pump power was observed in the 1200- to 1800-nm pump wavelength range, and a marked decrease in the terahertz emission efficiency beyond 2500 nm (pump photon energies <0.5 eV) suggests a ∼0.35-eV threshold pump photon energy for effective spintronic terahertz emission. The inferred threshold is supported by previous theoretical results on the onset energy of significant spin-filtering at the Fe-Pt interface, and confirmed by Fe/Pt electronic structure calculations in this present work. The results of terahertz time-domain emission spectroscopy show the sensitivity of spintronic terahertz emission to both the optical absorptance of the heterostructure and the energy-dependent spin transport, as dictated by the properties of the metallic thin films.

Terahertz time-domain ellipsometry with high precision for the evaluation of GaN crystals with carrier densities up to 1020 cm-3.

Gallium nitride (GaN) is one of the most technologically important semiconductors and a fundamental component in many optoelectronic and power devices. Low-resistivity GaN wafers are in demand and actively being developed to improve the performance of vertical GaN power devices necessary for high-voltage and high-frequency applications. For the development of GaN devices, nondestructive characterization of electrical properties particularly for carrier densities in the order of 1019 cm-3 or higher is highly favorable. In this study, we investigated GaN single crystals with different carrier densities of up to 1020 cm-3 using THz time-domain ellipsometry in reflection configuration. The p- and s-polarized THz waves reflected off the GaN samples are measured and then corrected based on the analysis of multiple waveforms measured with a rotating analyzer. We show that performing such analysis leads to a ten times higher precision than by merely measuring the polarization components. As a result, the carrier density and mobility parameters can be unambiguously determined even at high conductivities.

Dielectric property measurements of corneal tissues for computational dosimetry of the eye in terahertz band in vivo and in vitro.

The dielectric constant of the normal corneal tissue of a rabbit eye was obtained in vitro in the range from approximately 0.1 to 1 THz, and the drying process on the eye surface exposed to high-power terahertz waves was investigated by in vivo reflectance measurement using terahertz time-domain spectroscopy. When the rabbit eye was exposed to terahertz waves at 162 GHz for 6 min with an irradiation power of 360 or 480 mW/cm2, the reflectance temporally increased and then decreased with a temperature increase. Based on multiple-reflection calculation using the dielectric constant and anterior segment optical coherence tomography images, those changes in reflectance were attributed to drying of the tear and epithelium of the cornea, respectively. Furthermore, the drying progressed over a temperature increase of around 5°C under our exposure conditions. These findings suggest that the possibility of eye damage increases with the progress of drying and that the setting of the eye surface conditions can be a cause of disagreement between computational and experimental data of absorbed energy under high-level irradiation because reflectance is related to terahertz wave penetration in the eye tissue. The time-domain spectroscopic measurements were useful for the acquisition of the dielectric constant as well as for the real-time monitoring of the eye conditions during exposure measurement.

A modulation-doped heterostructure-based terahertz photoconductive antenna emitter with recessed metal contacts.

We present the implementation of an efficient terahertz (THz) photoconductive antenna (PCA) emitter design that utilizes high mobility carriers in the two-dimensional electron gas (2DEG) of a modulation-doped heterostructure (MDH). The PCA design is fabricated with recessed metal electrodes in direct contact with the 2DEG region of the MDH. We compare the performance of the MDH PCA having recessed contacts with a PCA fabricated on bulk semi-insulating GaAs, on low temperature-grown GaAs, and a MDH PCA with the contacts fabricated on the surface. By recessing the contacts, the applied bias can effectively accelerate the high-mobility carriers within the 2DEG, which increases the THz power emission by at least an order of magnitude compared to those with conventional structures. The dynamic range (62 dB) and bandwidth characteristics (3.2 THz) in the power spectrum are shown to be comparable with the reference samples. Drude-Lorentz simulations corroborate the results that the higher-mobility carriers in the MDH, increase the THz emission. The saturation characteristics were also measured via optical fluence dependence, revealing a lower saturation value compared to the reference samples. The high THz conversion efficiency of the MDH-PCA with recessed contacts at low optical power makes it an attractive candidate for THz-time domain spectroscopy systems powered by low power fiber lasers.

Evaluation of high-stability optical beats in laser chaos by plasmonic photomixing.

The stability of optical beats in a chaotically oscillating laser is compared to that of a free-running continuous-wave laser using a highly efficient plasmonic photomixer. Using a chaotically oscillating laser diode, stable optical beats are observed over an operation current range of 60-90 mA. The optical spectra are stable even with frequent mode hopping. In contrast, optical beats in a free-running continuous-wave laser are not stable compared to those of a chaotically oscillating laser, because of intermittent hopping of the laser modes. The high stability of chaotically oscillating lasers makes these lasers promising candidates for optical pump sources in terahertz time-domain spectroscopy systems.

Terahertz Magneto-Optic Sensor/Imager.

We are reporting a new type of compact magneto-optic sensor constructed from terahertz-wave spintronic emitter and electro-optic detector. The corresponding terahertz polarization output of the emitter and the detection phase-sensitivity of the detector depend on the vector of the external magnetic field. The emitter/detector pair consists of two small and thin wafers sandwiched together and capped with a thin gold mirror. As a result, the use of bulky terahertz steering/collection optics was completely eliminated in our magneto-optic imager. With such simple on-chip generation/detection scheme for terahertz time-domain setup in reflection-type geometry, we were able to record the raster-scanned image contrast of a permanent magnet in the proximity of the sensor surface. The contrast strongly varies with the magnet orientation and its position with respect to the sensor. The imager spatial resolution depends on chip optical quality for tight femtosecond-laser pump/probe cross-focusing at detector/mirror interface and terahertz generation/detection efficiency. In this respect, the chip robustness to the pump/probe fluences is also an important factor to consider.

Terahertz beam focusing through designed oblique metal-slit array.

Manipulation of propagating beams is essential in applications, and the potentially arising phenomena offer attractive optical components. However, the design of optical components using only naturally occurring materials has approached physical limits, and artificial materials such as metamaterials and metasurfaces are a way forward to open the door to sophisticated optical components. This paper shows manipulation of terahertz beams through designed oblique metal-slit arrays where a common metal-slit array does not perform as a lens. The oblique metal-slit array has a refractive index determined as a function of a steep angle. The lens consists of multiple metal plates with a designed oblique angle, and a convex output structure produces a focusing effect. We also suggest that the Brewster phenomenon in the lens can simply enhance the electric field intensity at the focal point. The Brewster condition of the lens is correlated with a jagged edged face on the input side with an appropriate metal-slit spacing and thickness. The phenomenon would be applicable to numerous promising components and applications such as gain-enhancement optical components and perfect impedance-matching polarizers.

Terahertz Radiation from Combined Metallic Slit Arrays.

We report an approach to efficiently generate terahertz radiation from a combined periodic structure. The proposed configuration is composed of two metallic slit arrays deliberately designed with different periodic length, slit width and depth. We found that the combination of the two slit arrays could provide special electromagnetic modes, which exhibit nonradiative property above the surface of one slit array and radiative property inside the other one. An electron beam holding proper energy could resonate with those modes to generate strong and directional electromagnetic radiations in the terahertz regime, indicating that the approach has the potential in developing high-performance terahertz radiation sources.

Randomized phase III trial of post-operative chemotherapy for patients with stage I/II/III small bowel adenocarcinoma (JCOG1502C, J-BALLAD).

A randomized phase III trial was initiated in May 2017 to confirm the superiority of post-operative therapy with capecitabine and oxaliplatin over observation in terms of relapse-free survival in patients with curatively resected small bowel adenocarcinoma. Total 150 patients will be enrolled from 20 Japanese institutions over a period of 6.5 years. Relapse-free survival is the primary endpoint, while the secondary endpoints are overall survival, disease-free survival as defined by the Japan Clinical Oncology Group (JCOG), disease-free survival as defined by the International Rare Cancer Initiative (IRCI), and adverse events. Global phase III trial of IRCI to confirm the superiority of post-operative chemotherapy for small bowel adenocarcinoma was started in the UK in August 2015 (ClinicalTrials.gov Identifier: NCT02502370). An integrated analysis of the IRCI trial and our study are planned. Our trial has been registered in the UMIN Clinical Trials Registry as UMIN000027280 (http://www.umin.ac.jp/ctr/index.htm).

Dose-finding and efficacy confirmation trial of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for locally advanced maxillary sinus cancer (Japan Clinical Oncology Group 1212): Dose-finding phase.

BACKGROUND: We are currently undertaking a multi-institutional prospective trial of the superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy for patients with T4aN0M0 or T4bN0M0 locally advanced maxillary sinus squamous cell carcinomas (SCC). We herein report the results of the dose-finding phase. METHODS: The dose-finding phase sought to evaluate the incidence of dose-limiting toxicities and determine the recommended number of cycles of the intra-arterial infusion of cisplatin. In this phase, 100 mg/m2 of cisplatin was administered intra-arterially weekly for 7 weeks with concomitant radiotherapy (70 Gy). RESULTS: All 18 patients received a full dose of radiotherapy. The number of cycles of cisplatin was 7 in 13 patients and 6 in 5 patients. The dose-limiting toxicities were observed in 5 patients. CONCLUSION: These results indicated that this therapy is safe and well-tolerated at 7 cycles of cisplatin, which was determined to be the recommended number of cycles for locally advanced maxillary sinus SCC.

Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment.

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years.

Polarization-variable emitter for terahertz time-domain spectroscopy.

We report on the progress in the development of linear polarization-variable multi-electrode emitters for terahertz time-domain spectroscopy. The results on its microfabrication, the finite element method modeling of appropriate bias distribution between electrodes, the finite-difference time-domain simulated spectral output, and actual experimental testing are presented. The rotation of the emitted terahertz field with linear polarization on an angle multiple of 45° can be achieved by synchronized bias and single polarizer rotations.

Cherenkov-phase-matched nonlinear optical detection and generation of terahertz radiation via GaAs with metal-coating.

Terahertz (THz) wave detection and emission via Cherenkov-phase-matched nonlinear optical effects at 1.55-µm optical wavelength were demonstrated using a GaAs with metal-coating (M-G-M) and bare GaAs as a reference sample in conjunction with a metallic tapered parallel-plate waveguide (TPPWG). The metal-coated GaAs is superior to the bare wafer both as a THz electro-optic detector and as an emitter. Significant improvements in the detection and emission efficiency were obtained by utilizing a metal-coating due to better confinement and lower loss of the THz waves propagating in the M-G-M compared with bare GaAs.

Influence of the watch and wait strategy on clinical outcomes of patients with follicular lymphoma in the rituximab era.

We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57 years, range: 19-85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75 months (range: 7-169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92 months (95 % CI, 60.1-NA) and 77 months (95 % CI, 65.1-107.6), respectively, which were not significantly different (P = 0.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95 % CI, 1.03-1.38, P < 0.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era.

Disseminated herpes zoster infection initially presenting with abdominal pain in patients with lymphoma undergoing conventional chemotherapy: A report of three cases.

Visceral disseminated varicella zoster virus (VZV) disease has a high mortality rate, and occurs in immunocompromised hosts, mostly subsequent to allogeneic stem cell transplantation. Only a few cases of this disease that onset during conventional chemotherapy in patients with lymphoma have been reported. The present study reports the cases of 3 patients with disseminated and visceral VZV infection undergoing treatment for follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. All 3 patients presented with initial symptoms of abdominal pain, and 2 patients demonstrated syndrome of inappropriate antidiuretic hormone and hepatitis. All patients developed widespread cutaneous dissemination, and all had a low cluster of differentiation 4 cell count or lymphocyte count at the time of VZV diagnosis and at least 4 month prior. With intravenous systemic acyclovir therapy (Cases 1 and 3, 1500 mg/day; Case 2, 750 mg/day), the patients achieved complete recovery by day 14 of therapy. Visceral disseminated VZV infection is not limited to patients undergoing stem cell transplantation, and may present with abdominal pain with or without skin eruption. Visceral infection may take a poor clinical course, therefore, in patients with prolonged duration of low lymphocyte count and/or long-term use of steroids, the prophylactic use of acyclovir may be considered.

Classical Hodgkin lymphoma primary refractory to brentuximab vedotin, with transformation to CD30-positive diffuse large B-cell lymphoma.

Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. It is highly effective for relapsed/refractory classical Hodgkin lymphoma (CHL), and has become a promising treatment option for these patients; however, approximately 25 % of patients are refractory to BV. Until now, the clinicopathologic features of CHL refractory to BV have not been well understood. Here, we report a patient with relapsed CHL with an unfavorable outcome, whose disease was primary refractory to BV and was histologically diagnosed as a transformation from mixed cellularity CHL to CD30-positive diffuse large B-cell lymphoma (DLBCL). The transformation to DLBCL showing high tumor density and high proliferative activity (Ki67 index >90 %) was possibly related to the primary refractory to BV and an aggressive clinical course, although the lymphoma was diffusely and strongly positive for CD30.