Publications by authors named "Masakazu Hori"

47 Publications

Combination therapy using trans-catheter aortic valve implantation and adaptive servo-ventilation in patient with aortic stenosis and heart failure.

J Cardiol Cases 2021 May 18;23(5):224-226. Epub 2020 Nov 18.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan.

Severe aortic stenosis sometimes accompanies advanced heart failure with reduced cardiac contractility (i.e. low-flow low-gradient aortic stenosis). The therapeutic strategy for the remaining heart failure following trans-catheter aortic valve implantation remains unknown. An 84-year-old man with six hospitalizations due to aortic stenosis and congestive heart failure with reduced ejection fraction was admitted to our institute. Heart failure remained following trans-catheter aortic valve implantation. Additional adaptive servo-ventilation therapy with optimal pressure setting determined by the ramp test further improved his heart failure symptoms. Combination therapy using trans-catheter aortic valve implantation and adaptive servo-ventilation might be a promising therapeutic tool to ameliorate heart failure with severe aortic stenosis. <; Adaptive servo-ventilation might be a promising therapy in patients with persistent congestive heart failure following trans-catheter aortic valve implantation for severe aortic stenosis.>.
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http://dx.doi.org/10.1016/j.jccase.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103330PMC
May 2021

Impact of the whole activated clotting time during Impella support on short-term prognosis.

J Artif Organs 2021 May 13. Epub 2021 May 13.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

Impella (Abiomed, Danvers, MA, USA) is a percutaneous trans-catheter left ventricular assist device. Anticoagulant therapy targeting whole activated clotting time (ACT) between 160 and 180 s is recommended to prevent pump thrombosis during support. However, we sometimes experience fatal bleeding despite achieving the target ACT range. Consecutive patients who received Impella support in our institute between March 2018 and October 2020 were included in this retrospective study. The association between the averaged ACT levels during the Impella support and 30-day mortality was investigated. A total of 36 patients (71 years old, 61% males) were included. Most of the patients were managed within the recommended therapeutic range of ACT, and the average ACT level was 162 s. The higher ACT group (> 168 s) had older age, smaller body mass index, and higher serum creatinine compared with the lower ACT group (p < 0.05 for all). A higher ACT level was an independent risk factor of 30-day mortality with an adjusted hazard ratio of 1.085 (95% confidence interval 1.037-1.154) with a cut-off level of 168 s. There were only two thromboembolic events. Patients managed with higher ACT levels had a higher risk of 30-day mortality during Impella support. A low-dose heparin purge solution might be recommended in patients with high-risk for bleeding events.
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http://dx.doi.org/10.1007/s10047-021-01271-7DOI Listing
May 2021

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Med Mol Morphol 2021 May 8. Epub 2021 May 8.

Department of Radiology, Sapporo Medical University School of Medicine, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.
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http://dx.doi.org/10.1007/s00795-021-00290-wDOI Listing
May 2021

Implication of heart rate optimization in patients with heart failure.

J Cardiol Cases 2021 Apr 27;23(4):163-165. Epub 2020 Nov 27.

The Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

Prognostic impact of heart rate reduction therapy using ivabradine, a selective inhibitor of I channel that purely reduces heart rate, in patients with heart failure with reduced ejection fraction and sinus tachycardia has been demonstrated. However, ideal heart rate remains unknown. We experienced an 80-year-old woman with reduced left ventricular ejection fraction who was hospitalized due to congestive heart failure. Following the ivabradine administration that decreased her heart rate from 100 bpm down to around 60 bpm, the "overlap" between E-wave and A-wave in the trans-mitral Doppler echocardiography diminished, accompanied by an improvement in cardiac output. Heart rate optimization targeting to diminish the overlap between E-wave and A-wave might maximize cardiac output and improve the clinical course via facilitated cardiac reverse remodeling. Further studies are warranted to validate the implication of therapeutic strategy to aggressively minimize the echocardiographic "overlap" by heart rate reduction therapy in heart failure patients.
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http://dx.doi.org/10.1016/j.jccase.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020069PMC
April 2021

Therapeutic Strategy for a Patient with Advanced Heart Failure and Schizophrenia Without Cardiac Replacement Therapies.

Int Heart J 2021 Mar 17;62(2):441-444. Epub 2021 Mar 17.

Second Department of Internal Medicine, University of Toyama.

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.
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http://dx.doi.org/10.1536/ihj.20-624DOI Listing
March 2021

Initial Experience With Tafamidis Treatment for Transthyretin Amyloid Cardiomyopathy.

Circ Rep 2020 Jul 21;2(8):420-424. Epub 2020 Jul 21.

Second Department of Internal Medicine, University of Toyama Toyoma Japan.

Transthyretin amyloid cardiomyopathy is a progressive disease with a poor prognosis. There had been no specific treatment for transthyretin amyloid cardiomyopathy until tafamidis received expanded approval in March 2019 in Japan. However, the clinical efficacy of tafamidis remains unknown. We initiated tafamidis treatment in 9 patients (median age 78 years; 89% male) from May 2019 to April 2020. Within 6 months after initiation, 1 patient discontinued prematurely and 2 patients were hospitalized due to worsening heart failure, with 1 of these patients discontinuing therapy. There were no significant changes in plasma B-type natriuretic peptide and serum troponin I concentrations over the 6-month treatment period, but interventricular septum thickness increased in 3 of 6 patients. Further evaluation of tafamidis therapy in a larger patient cohort with transthyretin amyloid cardiomyopathy is warranted to determine the optimal therapeutic strategy.
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http://dx.doi.org/10.1253/circrep.CR-20-0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819654PMC
July 2020

Joint effects of patch edges and habitat degradation on faunal predation risk in a widespread marine foundation species.

Ecology 2021 05 8;102(5):e03316. Epub 2021 Apr 8.

School of Marine Science, Virginia Institute of Marine Science, The College of William and Mary, Gloucester Point, Virginia, 23062-1346, USA.

Human activities degrade and fragment coastal marine habitats, reducing their structural complexity and making habitat edges a prevalent seascape feature. Though habitat edges frequently are implicated in reduced faunal survival and biodiversity, results of experiments on edge effects have been inconsistent, calling for a mechanistic approach to the study of edges that explicitly includes indirect and interactive effects of habitat alteration at multiple scales across biogeographic gradients. We used an experimental network spanning 17 eelgrass (Zostera marina) sites across the Atlantic and Pacific oceans and the Mediterranean Sea to determine (1) if eelgrass edges consistently increase faunal predation risk, (2) whether edge effects on predation risk are altered by habitat degradation (shoot thinning), and (3) whether variation in the strength of edge effects among sites can be explained by biogeographical variability in covarying eelgrass habitat features. Contrary to expectations, at most sites, predation risk for tethered crustaceans (crabs or shrimps) was lower along patch edges than in patch interiors, regardless of the extent of habitat degradation. However, the extent to which edges reduced predation risk, compared to the patch interior, was correlated with the extent to which edges supported higher eelgrass structural complexity and prey biomass compared to patch interiors. This suggests an indirect component to edge effects in which the impact of edge proximity on predation risk is mediated by the effect of edges on other key biotic factors. Our results suggest that studies on edge effects should consider structural characteristics of patch edges, which may vary geographically, and multiple ways that humans degrade habitats.
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http://dx.doi.org/10.1002/ecy.3316DOI Listing
May 2021

Prognostic implication of risk scoring systems in patients with cardiogenic shock supported by ECMO and Impella.

J Artif Organs 2021 Jan 3. Epub 2021 Jan 3.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

We experienced two refractory cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation and Impella percutaneous left ventricular assist device (ECPELLA). TVAD score, which was originally proposed to predict one-year mortality following left ventricular assist device implantation using four objective parameters, was retrospectively calculated using data of day 3 following ECPELLA initiations. One patient with estimated intermediate risk could achieve successful explantation of ECPELLA, whereas another patient with estimated high risk was expired despite explantation of extracorporeal membrane oxygenation. TVAD score might be a useful tool to risk stratify and construct next strategy (i.e., bridge to recovery or bridge to more intensive therapy) for those with ECPELLA, although further studies are warranted to validate this hypothesis.
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http://dx.doi.org/10.1007/s10047-020-01232-6DOI Listing
January 2021

Usefulness of HVAD Waveforms as Diagnostic Assistance for Cardiac Tamponade.

ASAIO J 2021 04;67(4):e90-e92

From the The Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

We experienced a 39-year-old male patient who converted paracorporeal left ventricular assist device to HeartWare ventricular assist device (HVAD; Medtronic, Framingham, MA) as bridge-to-transplant indication. On the 10th postoperative day, the HVAD flow waveform presented periodical low pulsatility pattern. Significant pericardial hematoma was observed on the imaging studies, and he showed pulsus paradoxus. He was highly suspected of cardiac tamponade and performed thoracotomy. HVAD waveform might be a useful tool to monitor and early suspect of postoperative cardiac tamponade to consider more intensive examinations and thoracotomy before hemodynamic deterioration, although further large-scale studies are warranted to strengthen our hypothesis.
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http://dx.doi.org/10.1097/MAT.0000000000001303DOI Listing
April 2021

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

Jpn J Clin Oncol 2020 Oct;50(11):1290-1297

Department of Radiology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Objective: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients.

Methods: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues.

Results: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230.

Conclusion: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.
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http://dx.doi.org/10.1093/jjco/hyaa149DOI Listing
October 2020

Implication of Ivabradine in Up-titrating Beta-blocker in a Patient with Advanced Heart Failure.

Intern Med 2021 Mar 21;60(6):897-900. Epub 2020 Oct 21.

The Second Department of Internal Medicine, University of Toyama, Japan.

Titration of beta-blockers is a gold-standard therapy in patients with heart failure and a reduced ejection fraction but is sometimes challenging to administer, given symptomatic hypotension. Ivabradine is a recently introduced selective I channel inhibitor that purely reduces the heart rate. We encountered a patient with advanced heart failure in whom a beta-blocker could not be up-titrated given his symptomatic hypotension. Following the initiation of ivabradine, an increase in blood pressure due to heart rate optimization, probably via an improvement in the cardiac output, allowed for the further up-titration of carvedilol, followed by a successful clinical course. Ivabradine might be a novel therapeutic tool to facilitate the up-titration of beta-blockers in patients with heart failure and hypotension.
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http://dx.doi.org/10.2169/internalmedicine.6061-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024963PMC
March 2021

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer.

Cancer Med 2020 11 22;9(22):8579-8588. Epub 2020 Sep 22.

Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Background: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223.

Methods: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS).

Results: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival.

Conclusions: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.
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http://dx.doi.org/10.1002/cam4.3459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666734PMC
November 2020

Regulation of Angiopoietin-2 Before and After Mechanical Circulatory Support Therapy.

ASAIO J 2021 01;67(1):53-58

From the Second Department of Internal Medicine; and.

Gastrointestinal bleeding (GIB) during mechanical circulatory support (MCS) is a major unsolved comorbidity. Inadequate activation of angiopoietin-2-related systems is considered as a major cause of GIB. However, the regulation of angiopoietin-2 remains unknown. Consecutive 20 patients who received continuous-flow MCS therapy (MCS group) and 12 with advanced heart failure (HF; HF group) were prospectively enrolled and their angiopoetin-2 levels were compared. Angiopoietin-2 level had a moderate correlation with log10 B-type natriuretic peptide (BNP; r = 0.39, p < 0.001). The MCS group had significantly higher angiopoietin-2 level divided by log10 BNP compared with the HF group (2.80 ± 0.20 vs. 1.88 ± 0.17, p < 0.001). Angiopoetin-2 had a moderate correlation with central venous pressure and C-reactive protein during the MCS support (r = 0.51 and r = 0.45, respectively). Higher angiopoietin-2 level divided by log10 BNP (> 4.3) was significantly associated with the occurrence of GIB with a hazard ratio of 296 (95% confidence interval 2.24-38620, p = 0.0224). Angiopoietin-2 was already elevated in the HF cohort and more elevated following MCS initiation. Among the MCS cohort, angiopoietin-2 was particularly elevated in patients with systemic congestion and inflammation and was associated with higher incidence of GIB.
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http://dx.doi.org/10.1097/MAT.0000000000001189DOI Listing
January 2021

Impact of the angle between aortic and mitral annulus on the occurrence of hemolysis during Impella support.

J Artif Organs 2020 Sep 14;23(3):207-213. Epub 2020 May 14.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.

Despite optimal management, we sometimes experience refractory hemolysis requiring extensive device speed reduction or continuous hemodiafiltration following Impella implantation. However, pre-procedural predictors of such a refractory hemolysis remain unknown. In this study, we investigated the pre-procedural factors, including the echocardiographic narrow angle between aortic and mitral annulus, associating with the occurrence of refractory hemolysis following Impella insertion. We enrolled 26 patients (71 years, 65% male) who received Impella insertion between March 2018 and November 2019. Among baseline characteristics, the angle between aortic and mitral annulus, < 126.5°, was an independent risk factor of refractory hemolysis with an adjusted hazard ratio of 7.840 (95% confidence interval 0.925-66.44) and was associated with lower 30-day survival (64% vs. 100%, p = 0.0116). The narrow angle between aortic and mitral annulus might be a useful tool to risk-stratify the occurrence of refractory hemolysis following Impella insertion.
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http://dx.doi.org/10.1007/s10047-020-01172-1DOI Listing
September 2020

Evaluation of the urethral α/β ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy.

Brachytherapy 2020 May - Jun;19(3):290-297. Epub 2020 Apr 2.

Department of Radiology, Sapporo Medical University, Sapporo, Hokkaido, Japan. Electronic address:

Purpose: To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer.

Methods And Materials: The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/β ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity.

Results: Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/β value was 0.5 or 1 Gy and t1/2 was 0.5-2.5 h. An uBED (α/β = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis.

Conclusions: We observed a significant correlation of uBED with GU toxicity when α/β was 0.5 or 1.0 Gy and t1/2 was 0.5-2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.
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http://dx.doi.org/10.1016/j.brachy.2020.02.007DOI Listing
January 2021

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer.

J Radiat Res 2020 Mar;61(2):265-274

Department of Radiology, Sapporo Medical University School of Medicine, Chuo-ku, S1 W16, Sapporo, Hokkaido 060-8543, Japan.

Combining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose-volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70-80 , 60-70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = -0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).
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http://dx.doi.org/10.1093/jrr/rrz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246069PMC
March 2020

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

Strahlenther Onkol 2020 Aug 17;196(8):725-735. Epub 2020 Jan 17.

Department of Radiology, Sapporo Medical University School of Medicine, S1W16, Chuo-Ku, 060-8543, Sapporo, Hokkaido, Japan.

Purpose: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters.

Materials And Methods: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples.

Results: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005).

Conclusion: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.
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http://dx.doi.org/10.1007/s00066-019-01571-1DOI Listing
August 2020

Spatially explicit modeling of metapopulation dynamics of broadcast spawners and stabilizing/destabilizing effects of heterogeneity of quality across local habitats.

J Theor Biol 2020 05 14;492:110157. Epub 2020 Jan 14.

National Research Institute of Fisheries and Environment of InlandSea, Japan Fisheries Research and Education Agency, Hatsukaichi, Hiroshima 739-0452, Japan. Electronic address:

Many coastal invertebrate species are broadcast spawners. These species have a highly sedentary adult stage and disperse by oceanic transport of planktonic larvae. One commercially important group of broadcast spawners is abalones, which live in suitable habitat patches of rock reefs that are discretely distributed. Because of these life-history and habitat characteristics, abalones tend to exhibit a metapopulation structure. Despite fisheries management and the release of juveniles, wild populations of broadcast spawners have undergone dramatic reductions in density due to overexploitation, which has been partly attributed to a failure to account for spatial structure. To clarify the relationship between the persistence of a metapopulation and the bottleneck that occurs during reproduction and dispersal processes caused by spatial structure, we developed a spatially explicit metapopulation model accounting for the effects of both life history and fishery pressure. By analyzing the model, we derived a metric to evaluate metapopulation quality as the leading eigenvalue of a non-negative matrix (the landscape matrix). Using this measure, we clarified that the effect of spatial structure on metapopulation stability is explained well by the mean and variance of parameter values across patches under the condition in which the heterogeneity of the metapopulation network is weak. In particular, the presence of both a higher average and higher variance of quality in the landscape could indicate stable fishery stocks under certain conditions. For example, when the decline in the mean longevity of local patch due to the fishery pressures gradually diminishes, the rescue effects by good patches would work more effectively than the negative effect of bad patches and then the stabilizing effect of spatial heterogeneity could be observed in a metapopulation. Furthermore, optimal patch characteristics for the improvement of quality strongly depend on specific parameter values. For example, when adult fertility is improved, a patch with higher "source" ability is more suitable. In contrast, when the settlement success of planktonic larvae is improved or fishery pressure is reduced, a patch with higher "buffer" ability is more suitable for the improvement of fishery management.
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http://dx.doi.org/10.1016/j.jtbi.2020.110157DOI Listing
May 2020

First Experience of Transfer with Impella 5.0 Over the Long Distance in Japan.

Int Heart J 2019 Sep 4;60(5):1219-1221. Epub 2019 Sep 4.

Second Department of Internal Medicine, University of Toyama.

We recently experienced a 43-year-old man with dilated cardiomyopathy transported under the Impella support to a high-volume left ventricular assist device (LVAD) center. Stabilized hemodynamics with the Impella and firm fixation of the device were important for safe transportation of the patient.
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http://dx.doi.org/10.1536/ihj.19-038DOI Listing
September 2019

A case of Takotsubo cardiomyopathy with cardiogenic shock after influenza infection successfully recovered by IMPELLA support.

J Artif Organs 2019 Dec 21;22(4):330-333. Epub 2019 Jun 21.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

We recently experienced a case of cardiogenic shock due to influenza-related Takotsubo cardiomyopathy with atrial tachycardia and respiratory distress syndrome. Temporary mechanical circulatory support by IMPELLA 2.5 improved end-organ failure and resulted in cardiac recovery with sinus rhythm conversion.
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http://dx.doi.org/10.1007/s10047-019-01112-8DOI Listing
December 2019

A case of cardiogenic shock due to acute coronary syndrome successfully recovered by percutaneous and paracorporeal left ventricular assist device.

J Artif Organs 2019 Sep 1;22(3):249-252. Epub 2019 Apr 1.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-City, 930-0194, Japan.

We recently experienced a 70-year-old woman with left main trunk-acute coronary syndrome who was initially supported by Impella 5.0 which converted to paracorporeal left ventricular assist device (LVAD) implantation as a bridge to recovery. Optimized guideline-directed medical therapy with cardiac rehabilitation resulted in successful explantation of LVAD and she discharged on foot.
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http://dx.doi.org/10.1007/s10047-019-01101-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685920PMC
September 2019

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Radiother Oncol 2018 11 21;129(2):409-414. Epub 2018 Sep 21.

Department of Radiology, Sapporo Medical University School of Medicine, Japan. Electronic address:

Background And Purpose: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC).

Material And Methods: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy.

Results: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors.

Conclusions: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.
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http://dx.doi.org/10.1016/j.radonc.2018.08.023DOI Listing
November 2018

An in vitro verification of strength estimation for moving an 125I source during implantation in brachytherapy.

J Radiat Res 2018 Jul;59(4):484-489

Quantum Energy Applications, Graduate School of Engineering, Hiroshima University, 1-4-1, Kagamiyama, Higashi-Hiroshima, Hiroshima, Japan.

This study aims to demonstrate the feasibility of a method for estimating the strength of a moving brachytherapy source during implantation in a patient. Experiments were performed under the same conditions as in the actual treatment, except for one point that the source was not implanted into a patient. The brachytherapy source selected for this study was 125I with an air kerma strength of 0.332 U (μGym2h-1), and the detector used was a plastic scintillator with dimensions of 10 cm × 5 cm × 5 cm. A calibration factor to convert the counting rate of the detector to the source strength was measured and then the accuracy of the proposed method was investigated for a manually driven source. The accuracy was found to be under 10% when the shielding effect of additional needles for implantation at other positions was corrected, and about 30% when the shielding was not corrected. Even without shielding correction, the proposed method can detect dead/dropped source, implantation of a source with the wrong strength, and a mistake in the number of the sources implanted. Furthermore, when the correction was applied, the achieved accuracy came close to within 7% required to find the Oncoseed 6711 (125I seed with unintended strength among the commercially supplied values of 0.392, 0.462 and 0.533 U).
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http://dx.doi.org/10.1093/jrr/rry021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054227PMC
July 2018

Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA.

Jpn J Clin Oncol 2018 Feb;48(2):167-174

Department of Radiology, Sapporo Medical University School of Medicine, Hokkaido, Japan.

Background: To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs).

Methods: The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR.

Results: In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity.

Conclusion: Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.
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http://dx.doi.org/10.1093/jjco/hyx181DOI Listing
February 2018

Latitude, temperature, and habitat complexity predict predation pressure in eelgrass beds across the Northern Hemisphere.

Ecology 2018 Jan;99(1):29-35

Oregon State University, Corvallis, Oregon, 97331, USA.

Latitudinal gradients in species interactions are widely cited as potential causes or consequences of global patterns of biodiversity. However, mechanistic studies documenting changes in interactions across broad geographic ranges are limited. We surveyed predation intensity on common prey (live amphipods and gastropods) in communities of eelgrass (Zostera marina) at 48 sites across its Northern Hemisphere range, encompassing over 37° of latitude and four continental coastlines. Predation on amphipods declined with latitude on all coasts but declined more strongly along western ocean margins where temperature gradients are steeper. Whereas in situ water temperature at the time of the experiments was uncorrelated with predation, mean annual temperature strongly positively predicted predation, suggesting a more complex mechanism than simply increased metabolic activity at the time of predation. This large-scale biogeographic pattern was modified by local habitat characteristics; predation declined with higher shoot density both among and within sites. Predation rates on gastropods, by contrast, were uniformly low and varied little among sites. The high replication and geographic extent of our study not only provides additional evidence to support biogeographic variation in predation intensity, but also insight into the mechanisms that relate temperature and biogeographic gradients in species interactions.
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http://dx.doi.org/10.1002/ecy.2064DOI Listing
January 2018

Local tumor control and DNA-PK activity of peripheral blood lymphocytes in prostate cancer patients receiving radiotherapy.

J Radiat Res 2017 Mar;58(2):225-231

Department of Radiology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Repair of DNA damage is critical for genomic stability, and DNA-dependent protein kinase (DNA-PK) has an important role in repairing double-strand breaks. We examined whether the DNA-PK activity of peripheral blood lymphocytes (PBLs) was related to biochemical (prostate-specific antigen: PSA) relapse and radiation toxicity in prostate cancer patients who have received radiotherapy. A total of 69 patients with localized adenocarcinoma of the prostate participated in this study. Peripheral blood was collected 2 years or later after radiotherapy and centrifuged, then DNA-PK activity was measured by a filter binding assay. The high DNA-PK activity group had a significantly higher PSA relapse-free survival rate than the low DNA-PK activity group. The 10-year PSA relapse-free survival was 87.0% in the high DNA-PK activity group, whereas it was 52.7% in the low DNA-PK activity group. Multivariate analysis showed the Gleason score and the level of DNA-PK activity were significant predictors of PSA relapse after radiotherapy. In addition, the low DNA-PK activity group tended to have a higher incidence of Grade 1-2 urinary toxicity than the high DNA-PK activity group. Prostate cancer patients with low DNA-PK activity had a higher rate of PSA relapse and a higher incidence of urinary toxicity. DNA-PK activity in PBLs might be a useful marker for predicting PSA relapse and urinary toxicity, possibly contributing to personalized treatment of prostate cancer.
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http://dx.doi.org/10.1093/jrr/rrw099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571613PMC
March 2017

Expression of Ku70 predicts results of radiotherapy in prostate cancer.

Strahlenther Onkol 2017 Jan 27;193(1):29-37. Epub 2016 Jul 27.

Department of Radiology, Sapporo Medical University School of medicine, 060-8543, Chuo-ku, Sapporo, Hokkaido, Japan.

Background And Purpose: Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse.

Patients And Methods: We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens.

Results: Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained.

Conclusion: Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.
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http://dx.doi.org/10.1007/s00066-016-1023-7DOI Listing
January 2017

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Med Mol Morphol 2017 Mar 23;50(1):25-33. Epub 2016 Jun 23.

Department of Radiology, Sapporo Medical University Schoolo of Medicine, S1W16, Chuo-Ku, Sapporo, 060-8543, Hokkaido, Japan.

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.
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http://dx.doi.org/10.1007/s00795-016-0144-5DOI Listing
March 2017

Using Acoustics to Determine Eelgrass Bed Distribution and to Assess the Seasonal Variation of Ecosystem Service.

PLoS One 2016 8;11(3):e0150890. Epub 2016 Mar 8.

Field Science Center for Northern Biosphere, Hokkaido University, 20-5 Benten-cho, Hakodate-city, Hokkaido, Japan.

Eelgrass beds are an important source of primary production in coastal ecosystems. Understanding seasonal variation in the abundance and distribution of eelgrass is important for conservation, and the objectives of this study were to 1) monitor seasonal variation in eelgrass beds using an acoustic monitoring method (Quantitative echo sounder) and 2) broadly quantify the carbon circulation function. We obtained acoustic data of eelgrass beds in coastal areas north and east of Ikunojima Island. Surveys were conducted nine times over the 3-year period from 2011 to 2013 in order to monitor seasonal variation. Acoustic data were obtained and used to estimate the spatial distribution of eelgrass by geostatistical methods. To determine supporting services, we determined carbon sink and carbon fixation by eelgrass beds using data from the National Research Institute of Fisheries and Environment of Inland Sea (2011). The height and distribution of eelgrass beds were at a maximum in May and at a minimum in November of each year. Distribution trends were different between the north and east areas. Supporting services showed the same patterns throughout the year. The area of distribution was considered to be coincident with the life history of eelgrass. Distribution differed by area and changed yearly due to the effects of bottom characteristics and wind direction. Quantifying the supporting services of eelgrass beds was shown to be useful for managing the conservation of coastal ecosystems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783055PMC
August 2016