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The objective of this study was to propose prognostic factors and optimal treatment strategies by analyzing the clinicopathological features and programmed death-ligand 1 (PD-L1) expression. We analyzed 31 patients diagnosed with uterine or ovarian melanoma between 1997 and 2017 in the Kansai Clinical Oncology Group/Intergroup. Twenty-four and seven patients with cervical and ovarian melanomas were included, respectively. Immune checkpoint inhibitors were used in seven patients, and the objective response rate was 40%. Notably, two patients with objective responses had a high PD-L1 expression. Ten and four patients with cervical and ovarian melanomas, respectively, had high PD-L1 immunohistochemical expressions. Multivariate analysis revealed that tumor stage was an independent prognostic factor for progression-free survival in patients with cervical melanomas. In patients with ovarian melanomas, the 1-year cumulative progression-free and overall survival rates were 0 and 29%, respectively. Kaplan-Meier analyses revealed that age60 years was associated with poorer progression-free and overall survivals in patients with ovarian melanomas. In patients with cervical melanomas, the 1-, 3-, and 5-year cumulative overall survival rates were 53, 32, and 16%, respectively. Histological atypia was associated with a poorer progression-free survival, but there was no difference in survival between patients who underwent radical hysterectomy and those who did not. The present study is a large cohort study of uterine and ovarian melanomas, which are aggressive tumors with a significantly poor prognosis, even after standard surgery and adjuvant therapy. The use of immune checkpoint inhibitors is a promising and effective treatment option.

The survival rate and quality of life of patients with recurrent cervical cancer and pleural effusion had been extremely poor until bevacizumab was approved. We report two cases of recurrent cervical cancer with remarkably decreased pleural effusion and a long survival rate after combination chemotherapy with bevacizumab. Case 1: A patient was diagnosed with stage IIB cervical adenocarcinoma and treated with concurrent chemoradiotherapy (CCRT), total hysterectomy, and paclitaxel/carboplatin (TC) therapy as the primary treatment. After the first recurrence had been treated with irinotecan–cisplatin therapy and radiotherapy, symptomatic pleural effusion emerged. Paclitaxel-cisplatin-bevacizumab (Pac-Cis-Bev) was administered during 13 cycles of chemotherapy to promptly relieve pleural effusion, respiratory distress, and back pain. She survived for more than a year and a half after starting Pac-Cis-Bev therapy. Case 2: A patient was diagnosed with stage IIIB cervical squamous cell carcinoma and pulmonary recurrence after CCRT. After 21 cycles of TC or Pac-Cis-Bev therapy, pleural effusion emerged. Topotecan–paclitaxel–bevacizumab (Topo-Pac-Bev) was administered for 12 cycles. Respiratory distress was relieved in 2 weeks and pleural effusion almost completely resolved after 2 months. We changed the treatment to ifosfamide and nedaplatin as pleural effusion exacerbated. However, this treatment was not effective; hence the patient was rechallenged with Topo-Pac-Bev therapy. Six cycles of Topo-Pac-Bev rechallenge therapy effectively suppressed pleural effusion. She survived for 2 years after pleural effusion appeared. Chemotherapy with bevacizumab is useful for both symptom relief and improvement in prognosis in patients with recurrent cervical cancer, despite being in the late phase.

This study introduces a conceptually new solvent suppression scheme with adiabatic inversion pulses for 1H-detected multidimensional solid-state NMR (SSNMR) of biomolecules and other systems, which is termed “Solvent suppression of Liquid signal with Adiabatic Pulse” (SLAP). 1H-detected 2D 13C/1H SSNMR data of uniformly 13C- and 15N-labeled GB1 sample using ultra-fast magic angle spinning at a spinning rate of 60 kHz demonstrated that the SLAP scheme showed up to 3.5-fold better solvent suppression performance over a traditional solvent-suppression scheme for SSNMR, MISSISSIPPI (Zhou and Rienstra, J Magn Reson 192:167–172, 2008) with 2/3 of the average RF power.

Radical hysterectomy and immediate sacral colpopexy using autologous fascia lata could be considered a treatment option for cervical cancer complicated by severe and symptomatic pelvic organ prolapse.

Background/Aim: To investigate the role and outcomes of radiation therapy (RT) for stage IVB uterine cervical cancer (UCC) patients with lung (oligo) metastases due to the lack of recent reports on the subject. Patients and Methods: The cohort for this retrospective study comprised 23 consecutive patients with UCC (squamous cell carcinoma, n=13) and lung metastases who had received pelvic RT. Ten had lung metastases only, including 7 with oligometastases (≤4 lung metastases); the remaining 13 also had other distant metastases. Results: Nine (39.1%) of the 22 patients (95.7%) completed RT without interruption. The 1-year primary progression-free rate was 95.2%. The 1-year overall survival rate was 47.2 % (estimated median survival: 9 months). Significant prognostic factors for survival included: i) ≤4 lung metastases (p=0.035), ii) unilateral lung metastases (p=0.039), iii) primary tumor diameter

Aim Endocervical curettage (ECC) at the time of conization has been reported to be effective for diagnosing cervical intraepithelial neoplasia and/or early stage cervical cancer. We aimed to verify the accuracy of ECC with conization. Methods We retrospectively analyzed the records of 540 patients with suspected neoplastic cervical lesions who underwent conization at the Yokohama City University Hospital from January 2008 to December 2015. To validate the effectiveness of ECC for evaluating endocervical lesions, histopathologic findings from ECC samples were compared with those from endocervical specimens obtained by conization. In patients who subsequently underwent hysterectomy, specimens of residual endocervical stump lesions were compared with the specimens obtained by ECC. Results ECC was performed in 58.9% of patients who underwent conization. Positive findings were only observed in 7.9%, while negative findings were found in 67.3% of ECC samples; however, 24.8% of the samples were inadequate for diagnosis. None of the patients had an upgraded diagnosis according to ECC results. The sensitivity of ECC in predicting endocervical stump lesions that were identified by conization specimens was 25.0%, the specificity was 94.2% and the positive predictive value was 55.0% (κ = 0.238; P < 0.001). ECC samples yielded a sensitivity of 42.9%, a specificity of 83.9%, and positive predictive value of 54.5% (κ = 0.284; P = 0.053) in predicting residual endocervical lesions in the uterus. Conclusions As it offers low sensitivity and positive predictive value, ECC at the time of conization is of limited benefit for evaluating endocervical lesions.

Background: To examine trends in the clinicopathological characteristics of vulvar cancer in Japan. Methods: This is a nationwide retrospective study examining consecutive women with vulvar cancer between 2001 and 2010 in Japan (n = 1061). Temporal trends in demographics, tumor characteristics, and survival were assessed by cohort-level analysis. The National Cancer Institute&rsquo, s Surveillance, Epidemiology, and End Result Program was used for external validation (n = 10,154). Results: The number of oldest-old women aged &ge, 80 years significantly increased (from 18.0% in 2001 to 30.6% in 2010, 70.5% relative increase) in the study period. A stage shift was observed, with stage I disease decreasing from 43.0% to 34.0% (21.0% relative decrease), and tumors with distant metastases increasing from 23.2% to 35.6% (53.3% relative increase, p &lt, 0.05). The number of women who underwent surgical treatment decreased from 84.0% to 69.7% (17.0% relative decrease), whereas utilization of radiotherapy increased from 34.4% to 43.2% (25.7% relative increase) over time (p &lt, 0.05). In the cohort-level analysis, the five-year survival rates significantly decreased from 2001 to 2010 (p &lt, 0.05), specifically, 66.9% to 51.0% for progression-free survival (23.7% relative decrease), 79.5% to 67.9% for cause-specific survival (14.6% relative decrease), and 74.9% to 62.3% for overall survival (16.9% relative decrease). In the patient-level analysis, oldest-old women were less likely to undergo surgical treatment and were independently associated with decreased survival (p &lt, 0.05). In the US cohort, the number of oldest-old women (25.2% to 27.8%) and the five-year cause-specific survival rate (81.8% to 79.9%) remained unchanged during the study period (p &gt, 0.05). Conclusion: Demographics and outcomes of vulvar cancer in Japan significantly changed during the study period. An increasing oldest-old population and a stage shift to more metastatic disease resulted in a cohort-level decrease in survival rates.

Background/Aim: The aim of this study was to define the outcome of radiation therapy for vulvar carcinoma, and to investigate the effectiveness of therapeutic and prophylactic inguinal lymph node (ILN) irradiation. Because reports about the treatment of ILN were limited. Patients and Methods: Thirty consecutive vulvar carcinoma patients were treated using external beam radiation therapy (EBRT) for definitive disease (n=25) or postoperatively (n=5). Twenty-four (80%) had squamous cell carcinoma (SCC). Tumor stages (2002 UICC) ranged from 0 to IVB, with no distant metastases. Results: The median total prescribed dose for primary tumor was 64.8 Gy. The 2-year overall survival rate was 25.3%. The outcome was significantly better in patients with ILNs60 Gy (p=0.002). Conclusions: ILN diameters ≤30 mm and prescribed doses over 60 Gy were associated with ILN control in patients with vulvar carcinoma.

This study assessed indicators of the need for insulin therapy and the effect of treatment on pregnancy outcomes in Japanese patients with gestational diabetes mellitus (GDM). All patients diagnosed with GDM were hospitalized for three days. Plasma glucose profiles in patients under strict dietary management and the characteristics of GDM patients with high daily glucose levels were investigated. Patients who failed to achieve glycemic targets were treated with insulin. Indicators of the need for insulin treatment were investigated. Pregnancy outcomes in patients prescribed dietary management and patients prescribed insulin treatment were compared. The study included 112 patients with GDM. GDM patients with high daily glucose levels in the hospital exhibited significantly higher 1-h and 2-h plasma glucose levels in oral glucose tolerance tests (OGTTs) at diagnosis. In our hospital, 102 GDM patients with singleton pregnancies were followed until delivery; 32 (31.3%) were treated with insulin. Univariate analysis identified significant associations of insulin requirement with family history of diabetes and with 1-h and 2-h OGTT values at diagnosis. Multivariate analysis showed that the 1-h OGTT plasma glucose level at diagnosis was an independent predictor of the need for insulin. In perinatal outcomes, insulin treatment was associated with low birth weight.

Ultra-fast magic-angle spinning (UFMAS) at a MAS rate (ωR/2π) of 60 kHz or higher has dramatically improved the resolution and sensitivity of solid-state NMR (SSNMR). However, limited polarization transfer efficiency using cross-polarization (CP) between 1H and rare spins such as 13C still restricts the sensitivity and multi-dimensional applications of SSNMR using UFMAS. We propose a novel approach, which we call decoherence-optimized tilted-angle CP (DOTA CP), to improve CP efficiency with prolonged lifetime of 1H coherence in the spin-locked condition and efficient band-selective polarization transfer by incorporating off-resonance irradiation to 1H spins. 13C CP-MAS at ωR/2π of 70–90 kHz suggested that DOTA CP notably outperformed traditional adiabatic CP, a de-facto-standard CP scheme over the past decade, in sensitivity for the aliphatic-region spectra of 13C-labeled GB1 protein and N-formyl-Met-Leu-Phe samples by up to 1.4- and 1.2-fold, respectively. 1H-detected 2D 1H/13C SSNMR for the GB1 sample indicated the effectiveness of this approach in various multidimensional applications.

Objective To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. Methods This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I–III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. Results Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506–16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701–6.547, p

Gallium nitride (GaN) and indium-gallium nitride (InxGa1-xN) thin films were directly grown on several non-single-crystalline substrates such as quartz glass and amorphous-carbon-coated graphite. The films were grown by using a molecular beam epitaxy apparatus having single or dual nitrogen radio-frequency plasma cells, and in addition, germanium (Ge) or magnesium (Mg) doping to the films was also attempted. Crystallinity, photoluminescence (PL) property, and electrical property of the obtained films were investigated. Highly c-axis oriented GaN and InxGa1-xN thin films were obtained on the non-single-crystalline substrates. Near-band-edge emissions were observed in their PL spectra and the intensities were strongly enhanced by Ge doping. Ge doping was also effective on reducing resistivity of the GaN thin films grown on the non-single-crystalline substrates. Electrochemical capacitance-voltage measurements were carried out on the Mg-doped GaN thin films; and p-type conduction in the films was confirmed.

Thin films of gallium nitride (GaN) and related nitride materials were prepared, and their properties as transparent conducting electrodes were investigated. GaN thin films were directly grown on sapphire single crystal substrates by the molecular beam epitaxy. Heavy doping of germanium was employed to reduce resistivity of the films, with sufficient reduction found to be possible while maintaining their epitaxial growth state. Optical transmission spectra of the films in the short wavelength region were slightly deteriorated by the heavy doping; however, this was successfully improved by growing GaN films under metal-rich conditions to increase the electron mobility and suppress unwanted increase of the carrier densities. In addition, the optical transmission spectra in the short wavelength region was improved also by alloying GaN with aluminum nitride, though the resistivities of these films were relatively higher than those of the unmodified GaN films. The prepared nitride thin films exhibited sufficiently suitable properties as transparent conducting electrodes for use in applications such as full-spectrum nitride-based solar cells.

Introduction Bevacizumab has been applied clinically to advanced and recurrent cervical cancer, after showing improved overall survival in the GOG 240 trial. We report two cases of patients with recurrent cervical cancer who showed remarkable decrease in pleural effusion by chemotherapy combined with bevacizumab. Case 1 A 41-year-old patient with stage IIB cervical adenocarcinoma who presented with cervical carcinoma recurrence in the lung and paraaortic/ supraclavicular lymph nodes after primary treatments with concurrent chemoradiotherapy (CCRT), total hysterectomy, and paclitaxel-carboplatin (TC) therapy. As symptomatic pleural effusion emerged after irinotecan-cisplatin therapy and radiotherapy, paclitaxel-cisplatin-bevacizumab (Pac-Cis-Bev) was administered and relieved the pleural effusion promptly and the respiratory distress and back pain symptoms over 13 months. Case 2 The second case involved a 53-year-old patient with stage IIIB cervical squamous cell carcinoma who had a pulmonary recurrence following treatment with CCRT. As pleural effusion emerged at the end of the six-month drug holiday, after a total of 21 cycles of TC or Pac-Cis-Bev therapy to treat the recurrence, topotecan-paclitaxel-bevacizumab (Topo-Pac-Bev) was administered. Respiratory distress was relieved in two weeks, and the pleural effusion disappeared almost completely after two months. The patient received 12 cycles of Topo-Pac-Bev, in total. Conclusion The present two patients have survived over three years, without problematic symptoms, after pulmonary recurrences with pleural effusion, despite that the three-year survival rate for recurrent/metastatic cervical cancer has been reported to be less than 5% without bevacizumab therapy. Chemotherapies that contain bevacizumab present promising regimens for recurrent cases with pleural effusion, despite the uncommon risks of bladder-vaginal or recto-vaginal fistulas.

Background Vulvar cancer is a rare malignancy. Its occurrence in Japan is 1/6-1/10 of that in the Western countries. Population-based statisics for vulvar cancer has been missing in Japan. To examine trends in clinico-pathological characteristics of vulvar cancer in Japan. Methods This is a nationwide retrospective study examining consecutive cases of women with invasive vulvar cancer in Japan between 2001-2010 (n = 1,061). Temporal trends of demographics, tumor characteristics, and survival outcome were assessed with cohort-level analysis. The National Cancer Institute’s Surveillance, Epidemiology, and End Result Program served as the external validation (n = 10,154). Results The number of oldest-old women aged ≥80 years significantly increased from 18.0% to 30.6% (70.5% relative increase) over time. There was a stage-shift observed, and stage I disease decreased from 43.0% to 34.0% (21.0% relative decrease) whereas tumors with inguino-femoral nodal or distant metastasis increased from 23.2% to 35.6% (53.3% relative increase) during the study period (P 0.05). Conclusions Demographics and outcomes of vulvar cancer in Japan have significantly changed during the study period: Increasing oldest-old population and stage-shift to more metastatic disease resulted in cohort-level decrease in survival rates. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

The double-acquisition scheme for efficient data collection of hypercomplex data (the States method) of a two-dimensional experiment is adopted to magic-angle hopping (MAH) and magic-angle turning (MAT) experiments, which are powerful methods to measure the principal values of the chemical shift anisotropy (CSA) in a powder sample. It is shown that the double acquisition MAT (DAMAT) sequence realizes the S/N ratio comparable to or better than those of other variants of the MAH/MAT sequences. In addition, we show that DAMAT has preferable features that there are no spinning sidebands in the indirect dimension, and no spectral shearing is necessary.

Endocervical curettage (ECC) at the time of conization has been reported to be effective for diagnosing cervical intraepithelial neoplasia and/or early stage cervical cancer. We aimed to verify the accuracy of ECC with conization.We retrospectively analyzed the records of 540 patients with suspected neoplastic cervical lesions who underwent conization at the Yokohama City University Hospital from January 2008 to December 2015. To validate the effectiveness of ECC for evaluating endocervical lesions, histopathologic findings from ECC samples were compared with those from endocervical specimens obtained by conization. In patients who subsequently underwent hysterectomy, specimens of residual endocervical stump lesions were compared with the specimens obtained by ECC.ECC was performed in 58.9% of patients who underwent conization. Positive findings were only observed in 7.9%, while negative findings were found in 67.3% of ECC samples; however, 24.8% of the samples were inadequate for diagnosis. None of the patients had an upgraded diagnosis according to ECC results. The sensitivity of ECC in predicting endocervical stump lesions that were identified by conization specimens was 25.0%, the specificity was 94.2% and the positive predictive value was 55.0% (κ = 0.238; P0.001). ECC samples yielded a sensitivity of 42.9%, a specificity of 83.9%, and positive predictive value of 54.5% (κ = 0.284; P = 0.053) in predicting residual endocervical lesions in the uterus.As it offers low sensitivity and positive predictive value, ECC at the time of conization is of limited benefit for evaluating endocervical lesions.

A new method for precise setting of the spinning angle to the magic angle by using a saddle coil is described. The coil, which is referred to as an X0 shim coil, is wound to produce a uniform static magnetic field B x perpendicular to the main magnetic field B 0 . The magnetic field felt by a sample is a vector sum of the main field B 0 and the transverse field B x produced by the X0 shim coil. Hence the angle between the spinner axis and the effective magnetic field can be controlled by current I supplied to the X0 shim coil, leading to precise angle adjustment without backlash accompanied with a mechanical system conventionally used. It is shown that the angle range achieved is ± 0.05 ° for I = ± 5 A at B 0 = 7 T.

This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We prepared spherical (20 and 40 nm in diameter), rod (40 × 10 nm), and cubic (40 × 40 × 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody production was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine production from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine production, including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.

Thin semiconducting barium titanate ceramic bars consisting of single grains joined together in series have been prepared, and the positive temperature coefficient of resistivity (PTCR) characteristics of strictly single-grain boundaries in the materials were investigated. The resistivity (R)-temperature (T) characteristics obtained for the present samples can be classified into typically three categories: (1) normal type PTCR characteristics, similar to those observed in usual ceramic samples, (2) saw-tooth type PTCR characteristics, characterized by an abrupt increase in resistivity by more than three orders of magnitude at the Curie point, immediately follwoed by a monotonous decrease in it, and (3) flat type R–T characteristics, with substantially little or no resistivity jump. Of these R–T characteristics, normal type PTCR characteristics were the most frequently observed (about 60%; a total of 65 samples were examined). Flat type R–T characteristics were least frequently (about 10%) observed. Single boundaries with these three types of PTCR characteristics exhibited essentially the same ferroelectric capacitance–temperature characteristic; this demonstrates that the temperature dependence of the dielectric constant above the Curie point was not responsible for the PTCR anomalies. Single boundaries with normal and saw-tooth type PTCR characteristics showed significantly nonlinear current-voltage characteristics above the Curie point, which may be interpreted to be caused by a current strongly affected by traps (or surface acceptor states) present at the grain boundaries.

As basic principles for deriving the equations of motion for dynamical systems, there are d’Alembert’s principle and the principle of virtual power. From the former Hamilton’s principle and Langage’s equations are derived, which are powerful tool for deriving the equation of motion of mechanical systems since they can give the equations of motion from the scalar energy quantities. When Hamilton’s principle is applied to nonholonomic systems, however, care has to be taken. In this paper, a unified approach for holonomic and nonholonomic systems is discussed based on the modified Hamilton’s principle. In the present approach, constraints for both of the holonomic and nonholonomic systems are expressed in terms of time derivative of the position, and their variations are treated similarly to the principle of virtual power, i.e. time and position are fixed in operation with respect to the variations. The approach is applied to a holonomic and a simple nonholonomic systems.Copyright © 2009 by ASME

Mg-doped high-In-content In x Ga1− x N (x ∼ 0.35) thin films were grown on a c-face sapphire substrate using an MBE apparatus having dual RF nitrogen plasma cells. The films showed p-type conduction under certain cell temperatures of Mg. The p-type conduction was confirmed by electrolyte-based capacitance–voltage measurement on an In x Ga1− x N:Mg/In2O3/sapphire structure, in addition to thermo-electromotive force measurements.