Investigating the timing and site of recurrence for ovarian clear cell carcinoma: Analysis of the JGOG/GCIG trial-JGOG 3017-A3.

BACKGROUND: This study was conducted to determine the optimal monitoring after initial treatment of ovarian clear cell carcinoma (OCCC) using data from patients enrolled in the Japanese Gynecologic Oncology Group (JGOG) 3017 study. The JGOG study evaluated the efficacy of an irinotecan and cisplatin combination regimen compared with that of a paclitaxel and carboplatin regimen for OCCC patients who underwent primary surgery. METHODS: Yielding 619 total patients in this study, to analyze progression-free and overall survival, the hazards over time were estimated using kernel smoothing curves to identify the peak of event occurrence. The number of progression events was summed by progression site, and the cumulative incidence proportion was estimated for the major progression sites, considering competing risks. RESULTS: The peak hazard for progression or death was observed at 12 months post-treatment, and most events were observed by 24 months. The hazard for death peaked at 18 months post-treatment, with most events being observed by 48 months. The hazard for lung, liver, and spleen metastases remained constant for 18 months post-treatment, with a decreasing trend thereafter; most events were observed by 18 months. The hazard for peritoneal dissemination was constant for 12 months, with a decreasing trend thereafter, with most exacerbations observed by 24 months. The risk of pelvic recurrence peaked at 6 months, with most exacerbations observed by 24 months. DISCUSSION: The incidence of progression events for OCCC peaked at 12 months and most progression events occurred within 24 months. Close follow-up for the initial 24 months post-treatment and fewer visits thereafter may be acceptable. However, closely monitoring symptoms and examining patients based on differences in progression rates at different sites may be important.

Field Induced Multiple Superconducting Phases in UTe_{2} along Hard Magnetic Axis.

The superconducting (SC) phase diagram in uranium ditelluride is explored under magnetic fields (H) along the hard magnetic b axis using a high-quality single crystal with T_{c}=2.1 K. Simultaneous electrical resistivity and ac magnetic susceptibility measurements discern low- and high-field SC (LFSC and HFSC, respectively) phases with contrasting field-angular dependence. Crystal quality increases the upper critical field of the LFSC phase, but the H^{*} of ∼15 T, at which the HFSC phase appears, is always the same through the various crystals. A phase boundary signature is also observed inside the LFSC phase near H^{*}, indicating an intermediate SC phase characterized by small flux pinning forces.

Longitudinal Spin Fluctuations Driving Field-Reinforced Superconductivity in UTe_{2}.

Our measurements of ^{125}Te NMR relaxations reveal an enhancement of electronic spin fluctuations above µ_{0}H^{*}∼15 T, leading to their divergence in the vicinity of the metamagnetic transition at µ_{0}H_{m}≈35 T, below which field-reinforced superconductivity appears when a magnetic field (H) is applied along the crystallographic b axis. The NMR data evidence that these fluctuations are dominantly longitudinal, providing a key to understanding the peculiar superconducting phase diagram in H∥b, where such fluctuations enhance the pairing interactions.

Robust Fermi-Surface Morphology of CeRhIn_{5} across the Putative Field-Induced Quantum Critical Point.

We report a comprehensive de Haas-van Alphen (dHvA) study of the heavy-fermion material CeRhIn_{5} in magnetic fields up to 70 T. Several dHvA frequencies gradually emerge at high fields as a result of magnetic breakdown. Among them is the thermodynamically important ß_{1} branch, which has not been observed so far. Comparison of our angle-dependent dHvA spectra with those of the non-4f compound LaRhIn_{5} and with band-structure calculations evidences that the Ce 4f electrons in CeRhIn_{5} remain localized over the whole field range. This rules out any significant Fermi-surface reconstruction, either at the suggested nematic phase transition at B^{*}≈30 T or at the putative quantum critical point at B_{c}≃50 T. Our results rather demonstrate the robustness of the Fermi surface and the localized nature of the 4f electrons inside and outside of the antiferromagnetic phase.

Fermi-Surface Instability in the Heavy-Fermion Superconductor UTe_{2}.

Transport measurements are presented up to fields of 29 T in the recently discovered heavy-fermion superconductor UTe_{2} with magnetic field H applied along the easy magnetization a axis of the body-centered orthorhombic structure. The thermoelectric power varies linearly with temperature above the superconducting transition, T_{SC}=1.5 K, indicating that superconductivity develops in a Fermi liquid regime. As a function of field the thermoelectric power shows successive anomalies which appear at critical values of the magnetic polarization. Remarkably, the lowest magnetic field instability for H∥a occurs for the same critical value of the magnetization (0.4 µ_{B}) than the first order metamagnetic transition at 35 T for field applied along the b axis. It can be clearly identified as a Lifshitz transition. The estimated number of charge carriers at low temperature reveals a metallic ground state distinct from LDA calculations indicating that strong electronic correlations are a major issue.

Harmonising clinical trials within the Gynecologic Cancer InterGroup: consensus and unmet needs from the Fifth Ovarian Cancer Consensus Conference.

The Gynecologic Cancer InterGroup (GCIG) Fifth Ovarian Cancer Consensus Conference (OCCC) was held in Tokyo, Japan from 7 to 9 November 2015. It provided international consensus on 15 important questions in 4 topic areas, which were generated in accordance with the mission statement to establish 'International Consensus for Designing Better Clinical Trials'. The methodology for obtaining consensus was previously established and followed during the Fifth OCCC. All 29 clinical trial groups of GCIG participated in program development and deliberations. Draft consensus statements were discussed in topic groups as well as in a plenary forum. The final statements were then presented to all 29 member groups for voting and documentation of the level of consensus. Full consensus was obtained for 11 of the 15 statements with 28/29 groups agreeing to 3 statements, and 27/29 groups agreeing to 1 statement. The high acceptance rate of the statements among trial groups reflects the fact that we share common questions, and recognise important unmet needs that will guide future research in ovarian cancer.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease.

This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials in ROC? The historical definition of using platinum-free interval (PFI) to categorise patients as having platinum-sensitive/resistant disease was replaced by therapy-free interval (TFI). TFI can be broken down into TFIp (PFI), TFInp (non-PFI) and TFIb (biological agent-free interval). Additional criteria to consider include histology, BRCA mutation status, number/type of previous therapies, outcome of prior surgery and patient reported symptoms. (ii) What are the control arms for clinical trials in ROC? When platinum is considered the best option, the control arm should be a platinum-based therapy with or without an anti-angiogenic agent or a poly (ADP-ribose) polymerase (PARP) inhibitor. If platinum is not considered the best option, the control arm could include a non-platinum drug, either as single agent or in combination. (iii) What are the endpoints for clinical trials in ROC? Overall survival (OS) is the preferred endpoint for patient cohorts with an expected median OS < or = 12 months. Progression-free survival (PFS) is an alternative, and it is the preferred endpoint when the expected median OS is > 12 months. However, PFS alone should not be the only endpoint and must be supported by additional endpoints including pre-defined patient reported outcomes (PROs), time to second subsequent therapy (TSST), or time until definitive deterioration of quality of life (TUDD).

Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis.

OBJECTIVE: To investigate the association between mid-trimester residual cervical length (CL) and the risk of preterm birth in pregnancies after abdominal radical trachelectomy (RT). DESIGN: Retrospective cohort study. SETTING: University hospital. POPULATION: A total of 33 deliveries after 22 weeks' gestation in 30 women who underwent abdominal RT including prophylactic cervical cerclage and perinatal care between January 2002 and May 2016. METHODS: The association between mid-trimester residual CL (the distance between the cerclage and the external cervical os) and gestational age at delivery was investigated. Receiver-operating characteristics (ROC) curve analysis was performed to estimate the optimal cut-off values of the mid-trimester residual CL for the prediction of preterm birth. MAIN OUTCOME MEASURES: Preterm birth before 34 weeks' gestation. RESULTS: Mid-trimester residual CL showed a significant correlation with gestational age at delivery (r = 0.36, P < 0.05). There was a significant difference in residual CL between women who did and those who did not give birth before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of 75%, positive predictive value of 55% and negative predictive value of 86% (area under ROC curve, 0.75). CONCLUSIONS: Mid-trimester residual CL is significantly correlated with gestational age at delivery. Residual CL assessment could be used to reassure physicians and women that there is only a small chance of preterm birth in pregnancies after abdominal RT. TWEETABLE ABSTRACT: Mid-trimester residual cervical length is a good predictor of preterm birth after radical trachelectomy.

Collapse of Ferromagnetism and Fermi Surface Instability near Reentrant Superconductivity of URhGe.

We present thermoelectric power and resistivity measurements in the ferromagnetic superconductor URhGe for a magnetic field applied along the hard magnetization b axis of the orthorhombic crystal. Reentrant superconductivity is observed near the spin reorientation transition at H_{R}=12.75 T, where a first order transition from the ferromagnetic to the polarized paramagnetic state occurs. Special focus is given to the longitudinal configuration, where both the electric and heat current are parallel to the applied field. The validity of the Fermi-liquid T^{2} dependence of the resistivity through H_{R} demonstrates clearly that no quantum critical point occurs at H_{R}. Thus, the ferromagnetic transition line at H_{R} becomes first order implying the existence of a tricritical point at finite temperature. The enhancement of magnetic fluctuations in the vicinity of the tricritical point stimulates the reentrance of superconductivity. The abrupt sign change observed in the thermoelectric power with the thermal gradient applied along the b axis together with the strong anomalies in the other directions is definitive macroscopic evidence that in addition a significant change of the Fermi surface appears through H_{R}.

Field-Induced Lifshitz Transition without Metamagnetism in CeIrIn(5).

We report high magnetic field measurements of magnetic torque, thermoelectric power, magnetization, and the de Haas-van Alphen effect in CeIrIn_{5} across 28 T, where a metamagnetic transition was suggested in previous studies. The thermoelectric power displays two maxima at 28 and 32 T. Above 28 T, a new, low de Haas-van Alphen frequency with a strongly enhanced effective mass emerges, while the highest frequency observed at low field disappears entirely. This suggests a field-induced Lifshitz transition. However, longitudinal magnetization does not show any anomaly up to 33 T, thus ruling out a metamagnetic transition at 28 T.

Reentrant superconductivity driven by quantum tricritical fluctuations in URhGe: evidence from

Our measurements of the ^{59}Co NMR spin-spin relaxation in URh_{0.9}Co_{0.1}Ge reveal a divergence of electronic spin fluctuations in the vicinity of the field-induced quantum critical point at H_{R}≈13 T, around which reentrant superconductivity (RSC) occurs in the ferromagnetic heavy fermion compound URhGe. We map out the strength of spin fluctuations in the (H_{b},H_{c}) plane of magnetic field components and show that critical fluctuations develop in the same limited region near the field H_{R} as that where RSC is observed. This strongly suggests these quantum fluctuations as the pairing glue responsible for the RSC. The fluctuations observed are characteristic of a tricritical point, followed by a phase bifurcation toward quantum critical end points.

Investigation of dyeing behavior of oxidative dye in fine structures of the human hair cuticle by nanoscale secondary ion mass spectrometry.

BACKGROUND/PURPOSE: In oxidative coloring, the hair cuticle layers are not only the penetration pathway for active ingredients but also one of the most important dyeing regions. The dyeing mechanism of oxidative dyes in fine structures of the cuticle remains unclear. To investigate the dyeing behavior of oxidative dyes in fine structures of the cuticle, hair cross-sections were analyzed by nanoscale secondary ion mass spectrometry (NanoSIMS). METHODS: The preparation method of hair cross-section for NanoSIMS measurement was improved. Improved hair cross-sections were analyzed using NanoSIMS. RESULTS: The cuticle layer thickness of the hair cross-section could be widened. It was confirmed that (12) C(-) ions were more strongly detected from endocuticle than from other fine structures of cuticle. The NanoSIMS (12) C(-) image and hue saturation intensity (HSI) D(-) /(1) H(-) ratio image of the hair, dyed with deuterium-labeled oxidative dye, indicated that the endocuticle had a higher D(-) /(1) H(-) ratio than the other fine structures of the cuticle. It was substantiated that more colored chromophores were fixated in the endocuticle than in other fine structures of the cuticle. CONCLUSION: The dyeing behavior of oxidative dyes in fine structures of hair cuticle was substantiated by NanoSIMS analysis using the improved hair cross-section preparation method.

Pathological factors associated with omental metastases in endometrial cancer.

PURPOSE OF INVESTIGATION: This study aimed to assess the role of omentectomy in the surgical therapy of endometrial cancer. MATERI- ALS AND METHODS: A retrospective study was performed in 98 patients who were pathologically diagnosed with endometrial cancer and had initially undergone surgical therapy at the present institution. This study analyzed the relationship between omental metastasis and clinicopathological factors. RESULTS: Omental metastasis was detected in nine patients (9%). On univariate analysis, significant number of omental metastatic lesions were detected in few cases by positive peritoneal cytology, adnexal metastasis, gross dissemination, and lymphovascular space involvement. On multivariate analysis, adnexal metastasis were a significant risk factor. The sensitivity of the spe- cial histological type and the specificity of the macroscopic peritoneal dissemination and adnexal metastasis were all high. CONCLUSION: Omentectomy plays a significant role in determining the exact surgical staging in cases with non-endometrioid cancer, adnexal metas- tasis, and macroscopic peritoneal dissemination.

Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor.

BACKGROUND: Although T-cell immunity is thought to be involved in the prognosis of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper antitumour immune responses. Thus, their mechanisms and overcoming strategies need to be investigated. METHODS: The role of NF-κB in human EOC cells and macrophages was evaluated by in vitro production of immunosuppressive IL-6 and IL-8 by EOC cells and in vivo analysis of immune responses in nude mice implanted with human EOC cells using an NF-κB inhibitor DHMEQ. RESULTS: In EOC patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-κB inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines. Immunosuppression of human DCs and macrophages by culture supernatant of EOC cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to nude mice implanted with human EOC resulted in the restoration of T-cell stimulatory activity of murine DCs along with the reduction of tumour accumulation and arginase expression of MDSCs. Nuclear factor-κB inhibition in tumour-bearing mice also enhanced antitumour effects of transferred murine naive T cells. CONCLUSIONS: NF-κB is involved in the immunosuppression induced by human EOC, and its inhibitor may restore antitumour immune responses, indicating that NF-κB is an attractive target for EOC treatment.

Symmetry of the excitations in the hidden order state of URu2Si2.

We perform polarized electronic Raman scattering on URu2Si2 single crystals at low temperature down to 8 K in the hidden-order state and under a magnetic field up to 10 T. The hidden-order state is characterized by a sharp excitation at 1.7 meV and a gap in the electronic continuum below 6.8 meV. Both Raman signatures are of pure A2g symmetry. By comparing the behavior of the Raman sharp excitation and the neutron resonance at Q0=(0,0,1), we provide new evidence, constrained by selection rules of the two probes, that the hidden-order state breaks the translational symmetry along the c axis such that Γ and Z points fold on top of each other. The observation of these distinct Raman features with a peculiar A2g symmetry as a signature of the hidden-order phase places strong constraints on current theories of the hidden-order in URu2Si2.

Large transverse thermoelectric effect induced by the mixed-dimensionality of Fermi surfaces.

Transverse thermoelectric effect, the conversion of longitudinal heat current into transverse electric current, or vice versa, offers a promising energy harvesting technology. Materials with axis-dependent conduction polarity, known as p × n-type conductors or goniopolar materials, are potential candidate, because the non-zero transverse elements of thermopower tensor appear under rotational operation, though the availability is highly limited. Here, we report that a ternary metal LaPt2B with unique crystal structure exhibits axis-dependent thermopower polarity, which is driven by mixed-dimensional Fermi surfaces consisting of quasi-one-dimensional hole sheet with out-of-plane velocity and quasi-two-dimensional electron sheets with in-plane velocity. The ideal mixed-dimensional conductor LaPt2B exhibits an extremely large transverse Peltier conductivity up to ∣αyx∣ = 130 A K-1 m-1, and its transverse thermoelectric performance surpasses those of topological magnets utilizing the anomalous Nernst effect. These results thus manifest the mixed-dimensionality as a key property for efficient transverse thermoelectric conversion.

Metamagnetic transition in UCoAl probed by thermoelectric measurements.

We report field and temperature dependent measurements of the thermoelectric power (TEP) and the Nernst effect in the itinerant metamagnet UCoAl. The magnetic field is applied along the easy magnetization c axis in the hexagonal crystal structure. The metamagnetic transition from the paramagnetic phase at zero field to the field induced ferromagnetic state is of first order at low temperatures and becomes a broad crossover above the critical temperature T(M)(⋆)∼11 K. The field dependence of the TEP reveals that the effective mass of the hole carriers changes significantly at the metamagnetic transition. The TEP experiment reflects the existence of different carrier types in good agreement with band structure calculations and previous Hall effect experiments. According to the temperature dependence of the TEP, no Fermi liquid behavior appears in the paramagnetic state down to 150 mK, but is achieved only in the field induced ferromagnetic state.

Evidence of strong correlations and coherence-incoherence crossover in the iron pnictide superconductor KFe2As2.

Using resistivity, heat-capacity, thermal-expansion, and susceptibility measurements we study the normal-state behavior of KFe2As2. Both the Sommerfeld coefficient (γ≈103 mJ mol(-1) K(-2)) and the Pauli susceptibility (χ≈4×10(-4)) are strongly enhanced, which confirm the existence of heavy quasiparticles inferred from previous de Haas-van Alphen and angle-resolved photoemission spectroscopy experiments. We discuss this large enhancement using a Gutzwiller slave-boson mean-field calculation, which shows the proximity of KFe2As2 to an orbital-selective Mott transition. The temperature dependence of the magnetic susceptibility and the thermal expansion provide strong experimental evidence for the existence of a coherence-incoherence crossover, similar to what is found in heavy fermion and ruthenate compounds, due to Hund's coupling between orbitals.

Magnetic structure of phase II in U(Ru(0.96)Rh(0.04))2Si2 determined by neutron diffraction under pulsed high magnetic fields.

We report neutron diffraction measurements on U(Ru(0.96)Rh(0.04))(2)Si(2) single crystal under pulsed high magnetic fields up to 30 T applied along the tetragonal c axis. The high-field experiments revealed that the field-induced phase II above 26 T corresponds to a commensurate up-up-down ferrimagnetic structure characterized by the wave vector q=(2/3,0,0) with the magnetic moments parallel to the c axis, which naturally explains the one-third magnetization plateau and the substantially changed Fermi surface in phase II. This a-axis modulated magnetic structure indicates that the phase II near the hidden order phase is closely related to the characteristic incommensurate magnetic fluctuations at Q(1)=(0.6,0,0) in the pure system URu(2)Si(2), in contrast to the pressure-induced antiferromagnetic order at Q(0)=(1,0,0).