Publications by authors named "Masahiko Shibuya"

97 Publications

Mechanisms of gradual pressure drop in angiographically normal left anterior descending and right coronary artery: Insights from wave intensity analysis.

J Cardiol 2021 Jan 25. Epub 2021 Jan 25.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan.

Background: This study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA).

Methods: Twelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium.

Results: The distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA.

Conclusions: The pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.
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http://dx.doi.org/10.1016/j.jjcc.2021.01.006DOI Listing
January 2021

Effects of Transcatheter Arterial Microembolization on Persistent Trapezius Myalgia Refractory to Conservative Treatment.

Cardiovasc Intervent Radiol 2021 Jan 20;44(1):102-109. Epub 2020 Oct 20.

Musculoskeletal Intervention Center, Okuno Clinic, 36-6 Hotel Atlas 2F, Chigasaki Chu-o, Tsuzukiku, Kanagawa, Japan.

Purpose: To evaluate the safety and efficacy of transcatheter arterial microembolization for patients with trapezius myalgia.

Materials And Methods: We retrospectively evaluated the prospectively collected data of patients with trapezius myalgia for > 6 months who were refractory to conservative treatment and were treated by transcatheter arterial microembolization between October 2017 and January 2019. Transcatheter arterial microembolization was performed using imipenem/cilastatin on the vessels of the transverse cervical artery, suprascapular artery, and circumflex scapular artery according to the region of pain.

Results: Forty-two patients were treated by transcatheter arterial microembolization and followed up for 6 months. No major adverse events occurred related to the procedures. The brief pain inventory worst pain scores significantly improved at 1, 2, 3, and 6 months after transcatheter arterial microembolization (8.6 ± 1.3 (before procedure) vs. 5.1 ± 2.9, 4.4 ± 2.9, 4.1 ± 2.8, and 3.9 ± 2.9, respectively, P < 0.001). The brief pain inventory pain interference scores, including general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life, also significantly decreased at 1, 2, 3, and 6 months after transcatheter arterial microembolization compared to those at baseline (all P < 0.01). The clinical success rate at 6 months after transcatheter arterial microembolization was 71.4% (95% confidence interval, 55.4-84.3%).

Conclusion: Transcatheter arterial microembolization is a safe and effective treatment for persistent trapezius myalgia. Further evaluation with a control group is needed to confirm the effects of transcatheter arterial microembolization.

Level Of Evidence: Level 4, Case Series.
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http://dx.doi.org/10.1007/s00270-020-02670-8DOI Listing
January 2021

Randomized phase II trial of adjuvant chemotherapy with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: TORG 0503.

Lung Cancer 2020 03 29;141:32-36. Epub 2019 Nov 29.

Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Objective: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, optimum chemotherapy regimen has not been determined. TORG0503 was undertaken to select a preferred platinum-based 3 generation regimen in this clinical setting.

Materials And Methods: Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institutions, and randomized to receive 3 cycles of docetaxel (60 mg/m) plus cisplatin (80 mg/m) (arm A) or paclitaxel (200 mg/m) plus carboplatin (AUC 6) (arm B) on day 1, every 3 weeks. The primary endpoint of the study was 2-year relapse free survival, and the key secondary endpoints included overall survival, feasibility and toxicity.

Results: 111 patients were randomized, 58 patients to arm A and 53 to arm B. Patient demographics were balanced between the two arms. 93 % (54/58) of patients on the arm A and 92 % (49/53) patients on the arm B completed the planned 3 cycles of chemotherapy. There was no treatment-related death in both arms. The 2 and 5 year relapse free survival was 74.5 % (95 %CI: 68.6-80.4) and 61.6 % in the arm A, and 72.0 % (95 %CI: 65.7-78.3) and 46.0 % in the arm B. The overall 2, 5-year survival was 89.7 %, 73.9 % in the arm A and 86.9 %, 67.5 % in the arm B.

Conclusion: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. We choose docetaxel plus cisplatin as the control regimen for the next clinical trial.
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http://dx.doi.org/10.1016/j.lungcan.2019.11.009DOI Listing
March 2020

Distribution of pressure gradients along the left anterior descending artery in patients with angiographically normal arteries.

Catheter Cardiovasc Interv 2020 07 14;96(1):E67-E74. Epub 2019 Oct 14.

Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Japan.

Objectives: This study tested the hypothesis that there is no decline of coronary pressure from the proximal to the distal left anterior descending coronary artery (LAD) of humans and swine.

Background: In the daily clinical practice, the fractional flow reserve (FFR) in the LAD is frequently lower than that in the other arteries in the presence of a similar degree of stenosis.

Methods: Twenty-six patients with angiographically normal LAD were prospectively enrolled. The coronary pressure ratio (mean distal/proximal coronary pressures at hyperemia) was measured at five different positions: 12, 10, 7, and 5 cm distal from the LAD ostium, and at the ostium of the LAD. The coronary pressure measurement was further investigated in a swine model without atherosclerosis.

Results: The coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (average: 0.85 ± 0.06 at 12 cm distal to the ostium). This finding was confirmed in swine model. The degree of the coronary pressure decrease during maximum hyperemia was similar in patients with and without evidence of minor plaque on intravascular ultrasound, however it was strongly associated with the amount of myocardium mass in the territory of the LAD.

Conclusions: Intracoronary pressure gradually decreases in proportion to the distance from the ostium in the LAD of humans and swine, regardless of the presence of minor atherosclerotic plaques. The degradation degree of the coronary pressure ratio during maximum hyperemia is enlarged in the presence of larger amount of myocardium mass in the territory of the LAD.
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http://dx.doi.org/10.1002/ccd.28544DOI Listing
July 2020

Multicenter study of zoledronic acid administration in non-small-cell lung cancer patients with bone metastasis: Thoracic Oncology Research Group (TORG) 1017.

Mol Clin Oncol 2019 Oct 23;11(4):349-353. Epub 2019 Jul 23.

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Kanagawa 240-8555, Japan.

Skeletal-related events (SREs) may occur at the time of first diagnosis in 20-30% of lung cancer patients with bone metastases. Several clinical trials have shown that zoledronic acid (ZA) is effective for decreasing SREs. The main objective of the present study was to discuss clinical data of ZA and compare the frequency of SREs with previous reports. All patients with non-small-cell lung cancer (NSCLC) with metastatic bone disease who were administered ZA at least twice between January 2008 and December 2009 were eligible for inclusion in the study. In total, 198 consecutive patients were identified. The median duration of ZA administration was 106 days [95% confidence interval (CI), 92-133 days], and the median number of ZA administrations was 4 (range, 2-41). The median time to first SRE in patients who experienced SRE following ZA treatment was 202 days (95% CI, 156-264 days). Among the 78 patients who had already experienced SRE prior to ZA treatment, 35 (45%) experienced SRE subsequently after starting ZA treatment. On the other hand, among the 120 patients without a history of SRE before starting ZA treatment, 42 (35%) experienced SRE after the start of ZA administration (P=0.16). No osteonecrosis of the jaw (ONJ) was reported in any of the patients. The present study revealed that ZA had a certain level of efficacy regardless of the presence or absence of prior SREs. However, the duration of ZA therapy was short in this study; further accumulation of data on the long-term prognosis and incidence rates of ONJ and other late complications of ZA therapy seems to be particularly important.
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http://dx.doi.org/10.3892/mco.2019.1903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713944PMC
October 2019

Effect of Transcatheter Arterial Microembolization on Phantom Limb Pain Persisting for 17 Years.

Cardiovasc Intervent Radiol 2019 Mar 13;42(3):471-474. Epub 2018 Nov 13.

Musculoskeletal Intervention Center, Okuno Clinic., 7-8-4, Roppongi, Minato-ku, Tokyo, Japan.

Phantom limb pain is a frequent consequence of the amputation; currently available treatments are far from satisfactory. The present report describes a case in which transcatheter arterial microembolization had a remarkable curative effect on phantom limb pain persisting for 17 years. The patient began feeling phantom limb sensations and brief intermittent pain following lower limb amputation above the knee in 2001. The frequency, intensity, and duration of the pain increased over time, and it was resistant to conservative treatments. Following transcatheter arterial microembolization in 2018, patient immediately experienced marked improvement. The pain has been infrequent, much less intense, and did not interfere with daily life 6 months posttreatment. Transcatheter arterial microembolization could be an alternative treatment option for phantom limb pain. LEVEL OF EVIDENCE: IV, Case Report.
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http://dx.doi.org/10.1007/s00270-018-2109-7DOI Listing
March 2019

Atherosclerotic Component of the Yellow Segment After Drug-Eluting Stent Implantation on Coronary Angioscopy - An Ex-Vivo Validation Study.

Circ J 2018 12 2;83(1):193-197. Epub 2018 Nov 2.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine.

Background: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut.

Conclusions: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.
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http://dx.doi.org/10.1253/circj.CJ-18-0671DOI Listing
December 2018

Impact of low tissue backscattering by optical coherence tomography on endothelial function after drug-eluting stent implantation.

Cardiovasc Interv Ther 2019 Apr 2;34(2):164-170. Epub 2018 Aug 2.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 6638501, Japan.

This study evaluated the impact of optical coherence tomography (OCT)-derived low-backscattered tissue on mid-term coronary endothelial function after drug-eluting stent (DES) implantation. Although OCT enables detailed in vivo evaluation of neointimal tissue characterization after DES implantation, its association with physiological vascular healing response is unclear. Thirty-three stable angina pectoris patients underwent OCT examination and endothelial function testing with intracoronary infusion of incremental doses of acetylcholine 8-month after DES implantation in a single lesion of the left anterior descending artery. Neointimal tissue was classified into two patterns based on the predominant OCT light backscatter: high backscatter and low backscatter. Although the presence of uncovered or malapposed stent strut was not associated with the degree of vasoconstriction, the degree of vasoconstriction was significantly greater in the DES with low-backscattered neointima than in the DES without low-backscattered neointima (- 32.1 ± 25.7 vs. - 4.1 ± 20.1%, p = 0.003). Moreover, there was an inverse linear relationship between low backscatter tissue index and degree of vasoconstriction after acetylcholine infusion (r = 0.50 and p = 0.003). The endothelium-dependent vasomotor response after 8-month of DES was impaired in patients with low neointimal tissue backscatter on OCT imaging. OCT assessment of low-backscattered tissue may be used as surrogate markers for impairment of endothelial function after DES.
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http://dx.doi.org/10.1007/s12928-018-0540-yDOI Listing
April 2019

Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents.

J Cardiol 2018 05 24;71(5):452-457. Epub 2017 Dec 24.

Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Background: The clinical benefit of second-generation drug-eluting stents (2nd DES) has been established, compared to first-generation drug-eluting stents (1st DES). However, pathological response after 2nd DES implantation remains unclear, particularly in the Japanese population.

Methods: Using specimens obtained by autopsy, we compared the histology between 2nd DES (41 sections) and 1st DES (38 sections) lesions within 1 year after stent implantation to evaluate early tissue reaction in Japanese patients. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin-eosin and Masson's trichrome staining. Ratio of covered stent struts was calculated, and the area of fibrin deposition was morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0-3).

Results: The ratio of covered struts and mean fibrin area of 2nd DES were 0.69±0.05 and 658.0±173.4μm. Those of 1st DES were 0.44±0.12 and 3107.5±1405.9μm. In the 2nd DES, there was significantly less fibrin deposition and a higher covered struts ratio. The inflammation score was significantly lower in 2nd DESs compared to 1st DESs (1.02±0.16 vs. 1.19±0.54, p<0.05).

Conclusions: Histopathological analysis showed advanced healing process in 2nd DES compared with 1st DES lesions. These results are consistent with clinical beneficial outcome of 2nd DES implantation.
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http://dx.doi.org/10.1016/j.jjcc.2017.11.009DOI Listing
May 2018

Impact of bioresorbable versus permanent polymer on longterm vessel wall inflammation and healing: a comparative drug-eluting stent experimental study.

EuroIntervention 2018 02;13(14):1670-1679

Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.

Aims: Drug-eluting stents (DES) have evolved to using bioresorbable polymers as a method of drug delivery. The impact of bioresorbable polymer on long-term neointimal formation, inflammation, and healing has not been fully characterised. This study aimed to evaluate the biological effect of polymer resorption on vascular healing and inflammation.

Methods And Results: A comparative DES study was performed in the familial hypercholesterolaemic swine model of coronary stenosis. Permanent polymer DES (zotarolimus-eluting [ZES] or everolimus-eluting [EES]) were compared to bioresorbable polymer everolimus-eluting stents (BP-EES) and BMS. Post implantation in 29 swine, stents were explanted and analysed up to 180 days. Area stenosis was reduced in all DES compared to BMS at 30 days. At 180 days, BP-EES had significantly lower area stenosis than EES or ZES. Severe inflammatory activity persisted in permanent polymer DES at 180 days compared to BP-EES or BMS. Qualitative para-strut inflammation areas (graded as none to severe) were elevated but similar in all groups at 30 days, peaked at 90 days in DES compared to BMS (p<0.05) and, at 180 days, were similar between BMS and BP-EES but were significantly greater in DES.

Conclusions: BP-EES resulted in a lower net long-term reduction in neointimal formation and inflammation compared to permanent polymer DES in an animal model. Further study of the long-term neointima formation deserves study in human clinical trials.
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http://dx.doi.org/10.4244/EIJ-D-17-00332DOI Listing
February 2018

Potential of New-Generation Double-Layer Micromesh Stent for Carotid Artery Stenting in Patients with Unstable Plaque: A Preliminary Result Using OFDI Analysis.

World Neurosurg 2017 Sep 26;105:321-326. Epub 2017 Jun 26.

Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.

Background: One disadvantage of carotid artery stenting (CAS) is a high incidence of distal embolism (DE) during or after the procedure. Patients with unstable plaque are considered at high risk for DE and plaque protrusion (PP) after stent placement, which can cause postprocedural ischemic complications. This study was conducted to compare the rate and size of PP between the CASPER stent, a new-generation double-layer micromesh stent, and conventional stents as assessed by optical frequency domain imaging (OFDI), and also to evaluate the efficacy of CAS with the CASPER stent in cases with unstable plaque.

Methods: The study group comprised 46 consecutive patients with unstable plaque, identified on magnetic resonance imaging, undergoing CAS with OFDI image acquisition. Cross-sectional OFDI images within the stented segments were evaluated at 0.125-mm intervals, and the rate and size of PP were compared between the CASPER stent and conventional stents.

Results: The CASPER stent was used in 9 patients. No procedural complications occurred. On OFDI analysis, the presence of PP was apparently lower in CASPER stent group compared with the conventional stent group (44% vs. 88%; P = 0.022). In addition, mean PP area was significantly smaller in the CASPER stent group (mean PP area, 0.013 ± 0.034 mm vs. 0.057 ± 0.09 mm; P = 0.006).

Conclusions: On OFDI evaluation after CAS, the degree of PP was significantly smaller in the CASPER stent group compared with the conventional stent group. This result provides new insight into the use of CAS to treat carotid artery stenosis with unstable plaque.
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http://dx.doi.org/10.1016/j.wneu.2017.05.171DOI Listing
September 2017

The distribution of calcified nodule and plaque rupture in patients with peripheral artery disease: an intravascular ultrasound analysis.

Heart Vessels 2017 Oct 2;32(10):1161-1168. Epub 2017 May 2.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 6638501, Japan.

In addition to plaque rupture (PR), calcified nodule (CN) may also have the potential to develop into arterial thrombus in the peripheral arteries. This study evaluated the distribution of plaque ruptures and calcified nodules in the peripheral arteries and their impact on the outcome of endovascular therapy (EVT). Consecutive 159 patients who underwent EVT with intravascular ultrasound guidance were enrolled. The position of CNs and PRs were assigned to any of common iliac artery, external iliac artery, common femoral artery, and superficial femoral artery. Forty-six (29%) patients had calcified nodule and twenty-eight (18%) patients had plaque rupture somewhere in the lower limb arteries. Although calcified nodules were evenly distributed throughout the length of the arteries plaque ruptures were predominantly located in the proximal segment of the iliofemoral arteries. Stent expansion ratio was significantly smaller in the target arteries with calcified nodules than in those with plaque rupture. Multivariate logistic regression analysis identified hemodialysis as an independent clinical predictor of calcified nodule (odds ratio 8.15, 95% confidence interval 1.73-38.3; P = 0.008). CN definitely affects incomplete stent deployment in the peripheral artery contributing to adverse events, on the other hand, PR has more acceptable outcomes after stent implantation. In the clinical setting, it is important that we realize the features of peripheral artery disease and its patient characteristics which having CNs and PRs to make a strategy for revascularization.
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http://dx.doi.org/10.1007/s00380-017-0984-5DOI Listing
October 2017

Preclinical in vivo long-term evaluation of the novel Mitra-Spacer technology: experimental validation in the ovine model.

EuroIntervention 2017 Jun;13(3):272-279

CRF Skirball Center for Innovation, Cardiovascular Research Foundation, Orangeburg, NY, USA.

Aims: The Mitra-Spacer (Cardiosolutions, Bridgewater, MA, USA) is designed to treat mitral regurgitation by introducing a dynamic spacer that constantly adapts to the changing haemodynamic conditions during the cardiac cycle. We aimed to evaluate the performance and safety of this device in the chronic ovine model.

Methods And Results: Eight sheep were enrolled in this study. Through a left thoracotomy, the Mitra-Spacer was inserted via the transapical approach and advanced into the left atrium (LA) under imaging guidance. Device performance and safety were evaluated up to 90 days using fluoroscopy, echocardiography and histopathology. The volume within the balloon spacer shifted during the cardiac cycle in all cases. Seven animals survived up to 90 days for terminal imaging and tissue harvest. Echocardiography showed no change in left ventricle (LV) ejection fraction from baseline to 90 days. There were no observations of changes in LV diastolic function, pulmonary vein inflow, or tricuspid valve function. Histological analysis demonstrated no significant injury to the mitral apparatus.

Conclusions: In the healthy ovine model, Mitra-Spacer implantation was feasible and safe. At 90 days, no evidence of structural damage to the mitral apparatus or deterioration of cardiac performance was demonstrated.
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http://dx.doi.org/10.4244/EIJ-D-16-00609DOI Listing
June 2017

Impact of stent diameter on vascular response after self-expanding paclitaxel-eluting stent implantation in the superficial femoral artery.

J Cardiol 2017 Oct 21;70(4):346-352. Epub 2017 Feb 21.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan. Electronic address:

Background: The optimal sizing of self-expanding paclitaxel-eluting stents (PES) in the treatment for superficial femoral artery (SFA) lesions is unclear. This study sought to investigate the influence of PES diameter on stent patency in SFA lesions using optical frequency domain imaging (OFDI).

Methods: A total of 20 de novo SFA lesions were randomized 1:1 to receive either self-expanding PES with a nominal diameter of 6mm or 8mm. Follow-up angiography and OFDI was scheduled six months after stent implantation, and volumetric OFDI analysis was performed to evaluate vascular response to the stents. Volume index (VI) was defined as the volume divided by the stent length. The primary end point was lumen VI at the 6-month follow-up. Secondary end point was minimum lumen diameter (MLD) by quantitative vascular angiography (QVA) at the follow-up.

Results: Stent length was 78.0±23.9mm in the 6-mm group and 70.0±23.6mm in the 8-mm group (p=0.46). Baseline QVA data were also similar between the two groups. MLD immediately after stent implantation was similar between the two groups (4.2±0.5mm in the 6-mm group and 3.9±0.5mm in the 8-mm group, p=NS). At the 6-month follow-up, MLD was greater in the 8-mm group compared to the 6-mm group (4.0±1.0mm vs. 3.2±0.4mm, p<0.05). Stent VI was larger in the 8-mm group (28.4±6.7mm/mm vs. 22.2±1.2mm/mm, p=0.01). Neointimal VI was similar between the two groups (5.8±2.9mm/mm vs. 5.2±2.6mm/mm, p=0.68). Lumen VI was greater in the 8-mm group (23.2±7.6mm/mm vs. 17.3±2.6mm/mm, p=0.04).

Conclusions: Chronic stent enlargement resulted in greater lumen area after implantation of self-expanding PES with a large diameter at the mid-term follow-up. Stent diameter might be important for stent patency in procedure with PES for SFA lesions.
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http://dx.doi.org/10.1016/j.jjcc.2016.12.011DOI Listing
October 2017

Comparing the vascular response in implantation of self-expanding, bare metal nitinol stents or paclitaxel-eluting nitinol stents in superficial femoral artery lesions: a serial optical frequency domain imaging study.

EuroIntervention 2016 Dec;12(12):1551-1558

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Aims: This study sought to investigate differences in vascular response between self-expanding bare metal nitinol stents (BMS) and paclitaxel-eluting nitinol stents (PES), in superficial femoral artery (SFA) disease, using optical frequency domain imaging (OFDI).

Methods And Results: Six months after stent implantation, follow-up quantitative vascular angiography (QVA) and OFDI assessment were scheduled to evaluate vascular response. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was OFDI-derived late lumen area loss, defined as lumen VI post stent implantation minus lumen VI at follow-up. A total of 28 SFA lesions were analysed, with cases randomised to receive either BMS or PES implantation. QVA-derived diameter stenosis at six-month follow-up was lower in the PES group than in the BMS group (28.5% vs. 39.7%, p=0.04). After six months, BMS VI increased by 33.8% (20.7±3.7 to 27.7±3.5 mm3/mm), whilst PES exhibited an increase of 32.1% (19.0±2.3 to 25.1±4.7 mm3/mm). Neointimal VI was smaller (7.4±2.6 mm3/mm vs. 10.5±3.2 mm3/mm, p<0.01) and late lumen area loss was lower (2.9±1.3 mm3/mm vs. 5.6±2.8 mm3/mm, p<0.01) in the PES group.

Conclusions: Serial volumetric OFDI analyses confirmed significantly smaller amounts of neointimal tissue and lower late lumen area loss following PES implantation for SFA lesions at short-term follow-up.
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http://dx.doi.org/10.4244/EIJ-D-15-00399DOI Listing
December 2016

Four-year polymer biocompatibility and vascular healing profile of a novel ultrahigh molecular weight amorphous PLLA bioresorbable vascular scaffold: an OCT study in healthy porcine coronary arteries.

EuroIntervention 2016 12;12(12):1510-1518

CRF-Skirball Center for Innovation, New York, NY, USA.

Aims: The vascular healing profile of polymers used in bioresorbable vascular scaffolds (BRS) has not been fully characterised in the absence of antiproliferative drugs. In this study, we aimed to compare the polymer biocompatibility profile and vascular healing response of a novel ultrahigh molecular weight amorphous PLLA BRS (FORTITUDE®; Amaranth Medical, Mountain View, CA, USA) against bare metal stent (BMS) controls in porcine coronary arteries.

Methods And Results: Following device implantation, optical coherence tomography (OCT) evaluation was performed at 0 and 28 days, and at one, two, three and four years. A second group of animals underwent histomorphometric evaluation at 28 and 90 days. At four years, both lumen (BRS 13.19±1.50 mm2 vs. BMS 7.69±2.41 mm2) and scaffold areas (BRS 15.62±1.95 mm2 vs. BMS 8.65±2.37 mm2) were significantly greater for BRS than BMS controls. The degree of neointimal proliferation was comparable between groups. Histology up to 90 days showed comparable healing and inflammation profiles for both devices.

Conclusions: At four years, the novel PLLA BRS elicited a vascular healing response comparable to BMS in healthy pigs. Expansive vascular remodelling was evident only in the BRS group, a biological phenomenon that appears to be independent of the presence of antiproliferative drugs.
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http://dx.doi.org/10.4244/EIJ-D-16-00308DOI Listing
December 2016

Biological effect on restenosis and vascular healing of encapsulated paclitaxel nanocrystals delivered via coated balloon technology in the familial hypercholesterolaemic swine model of in-stent restenosis.

EuroIntervention 2016 Oct;12(9):1164-1173

CRF Skirball Center for Innovation, Orangeburg, NY, USA.

Aims: The aim of this study was to evaluate the biological efficacy of a novel lower-dose (2.5 µg/mm2) encapsulated paclitaxel nanocrystal-coated balloon (Nano-PCB) in the familial hypercholesterolaemic swine (FHS) model of iliofemoral in-stent restenosis.

Methods And Results: Nano-PCB pharmacokinetics were assessed in 20 femoral arteries (domestic swine). Biological efficacy was evaluated in ten FHS: 14 days following bare metal stent implantation each stent segment was randomised to a clinically available PCB (IN.PACT, n=14), the Nano-PCB (n=14) or an uncoated balloon (n=12). Angiographic, optical coherence tomography and histological evaluation was performed at 28 days after treatment. Arterial paclitaxel concentration was 120.7 ng/mg at one hour and 7.65 ng/mg of tissue at 28 days with the Nano-PCB. Compared to the control uncoated group, both PCBs significantly reduced percent area stenosis (Nano-PCB: 36.0±14.2%, IN.PACT: 29.3±9.2% vs control: 67.9±15.1%, p<0.001). Neointimal distribution in the entire stent length was more homogenous in the Nano-PCB. Histological evaluation showed comparable degrees of neointimal proliferation in both PCBs; however, the Nano-PCB showed slightly higher levels of neointimal maturity and endothelialisation.

Conclusions: Lower-dose encapsulated paclitaxel nanocrystals delivered via a coated balloon displayed comparable biological efficacy with superior healing features compared to a clinically validated PCB technology.
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http://dx.doi.org/10.4244/EIJV12I9A188DOI Listing
October 2016

Comparative Characterization of Biomechanical Behavior and Healing Profile of a Novel Ultra-High-Molecular-Weight Amorphous Poly-l-Lactic Acid Sirolimus-Eluting Bioresorbable Coronary Scaffold.

Circ Cardiovasc Interv 2016 10;9(10)

From the CRF-Skirball Center for Innovation, Orangeburg, NY (Y.C., P.G., M.S., J.C.M., G.B.C., G.L.K., J.F.G.); Amaranth Medical, Inc, Mountain View, CA (K.R., C.L., E.A.E., D.D.); and 3rd Department of Cardiology, Medical University of Silesia, Katowice, Poland (P.G.).

Background: Clinically available bioresorbable scaffolds (BRS) rely on polymer crystallinity to achieve mechanical strength resulting in limited overexpansion capabilities and structural integrity when exposed to high-loading conditions. We aimed to evaluate the biomechanical behavior and vascular healing profile of a novel, sirolimus-eluting, high-molecular-weight, amorphous poly-l-lactic acid-based BRS (Amaranth BRS).

Methods And Results: In vitro biomechanical testing was performed under static and cyclic conditions. A total of 99 devices (65 Amaranth BRS versus 34 Absorb bioresorbable vascular scaffold [BVS]) were implanted in 99 coronary arteries of 37 swine for pharmacokinetics and healing evaluation at various time points. In the Absorb BVS, the number of fractures per scaffold seen on light microscopy was 6.0 (5.0-10.5) when overexpanded 1.0 mm above nominal values (≈34%). No fractures were observed in the Amaranth BRS group at 1.3 mm above nominal values (≈48% overexpansion). The number of fractures was higher in the Absorb BVS on accelerated cycle testing over time (at 24K cycles=5.0 [5.0-9.0] Absorb BVS versus 0.0 [0.0-0.5] Amaranth BRS). Approximately 90% of sirolimus was found to be eluted by 90 days. Optical coherence tomography analysis demonstrated lower percentages of late scaffold recoil in the Amaranth BRS at 3 months (Amaranth BRS=-10±16.1% versus Absorb BVS=10.7±13.2%; P=0.004). Histopathology analysis revealed comparable levels of vascular healing and inflammatory responses between both BRSs up to 6 months.

Conclusions: New-generation high-molecular-weight amorphous poly-l-lactic acid scaffolds have the potential to improve the clinical performance of BRS and provide the ideal platform for the future miniaturization of the technology.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.116.004253DOI Listing
October 2016

Recurrent coronary artery dissection of left main trunk initially presented with normal coronary angiography.

J Cardiol Cases 2016 Dec 7;14(6):164-167. Epub 2016 Sep 7.

Division of Cardiovascular Medicine and Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

Although spontaneous coronary artery dissection (SCAD) is usually diagnosed by coronary angiography, diagnosis may be missed because of various presentations and imperfections of coronary angiography. We report a case of a 41-year-old female with pregnancy-related SCAD who presented with cardiac arrest. Initial coronary angiography was normal without intimal flap. Unexpectedly, 4 days after admission, SCAD in left main trunk was revealed with recurrent myocardial infarction. Intimal flap was sealed at the time of first angiography and this is an interesting point that made us report this case. SCAD is a rare but not negligible cause of not only acute myocardial infarction but also sudden cardiac arrest even if first coronary angiography is normal. < In a case of a young post-partum woman with resuscitated sudden cardiac arrest who has normal coronary artery, intensive observation is needed. We should be aware that spontaneous coronary artery dissection is a rare but not negligible cause even if initial coronary angiography is normal.>.
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http://dx.doi.org/10.1016/j.jccase.2016.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283730PMC
December 2016

Impact of analysis interval size on the quality of optical frequency domain imaging assessments of stent implantation for lesions of the superficial femoral artery.

Catheter Cardiovasc Interv 2017 Mar 12;89(4):735-745. Epub 2016 Aug 12.

Division of Cardiovascular Medicine and Coronary Heart Disease Hyogo College of Medicine, Nishinomiya, Japan.

Objectives: This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA).

Background: No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries.

Methods: OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6-month follow-up. Initially, lumen and stent borders were traced at 1-mm axial intervals. Volumes were calculated using a PC-based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2-mm and 5-mm intervals, thereby reducing the number of cross-sectional image frames analyzed.

Results: The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm between MLA values from the 1-mm and 2-mm interval analyses, and 2.2 mm between MLA values from the 1-mm and 5-mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals.

Conclusions: Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.26673DOI Listing
March 2017

Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.

Int J Cardiol 2016 Oct 9;221:1043-7. Epub 2016 Jul 9.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan.

Background: Optical coherence tomography (OCT) is one of the tools trying to distinguish neoatherosclerosis from other neointimal tissue but its role has to be still validated. This study evaluated the diagnostic accuracy of OCT for characterization of lipid-atherosclerotic neointima following drug-eluting stent (DES) implantation.

Methods: Twelve stented coronary arteries from the 7 autopsy hearts were imaged by OCT. These OCT images were compared with histology. By OCT, the morphological appearances of neointima were classified into three patterns: homogeneous pattern, heterogeneous pattern with visible strut, or heterogeneous pattern with invisible strut.

Results: Of 21 histological cross-sections, 6 were categorized as homogeneous patterns (29%), 11 as heterogeneous patterns with visible stent strut (52%), and 4 as heterogeneous patterns with invisible stent strut (19%). All homogeneous patterns were composed of smooth muscle cells with collagen fibers. The heterogeneous patterns with visible stent strut included proteoglycan-rich myxomatous matrix and calcium deposition. On the other hand, the heterogeneous patterns with invisible stent strut comprised atheromatous tissue, including a large amount of foam cell accumulation (25%) or large fibroatheroma/necrotic core (75%) inside the stent struts within neointima. The optical attenuation coefficient was highest in the heterogeneous pattern with invisible stent strut due to scattering of light by atheromatous tissue.

Conclusion: The heterogeneous patterns with invisible stent strut on OCT imaging identify the presence of lipid-atherosclerotic tissue within neointima after DES. This may suggest the potential capability of OCT based on visualization of stent struts for discriminating atheromatous formation within neointima from other neointimal tissue.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.110DOI Listing
October 2016

Erratum to: Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma.

BMC Cancer 2016 Apr 15;16:272. Epub 2016 Apr 15.

Department of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan.

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http://dx.doi.org/10.1186/s12885-016-2309-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833961PMC
April 2016

Histopathological validation of optical frequency domain imaging to quantify various types of coronary calcifications.

Eur Heart J Cardiovasc Imaging 2017 Mar;18(3):342-349

Cardiovascular Division, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 6638501, Japan.

Aims: This study evaluated whether optical frequency domain imaging (OFDI) could identify various coronary calcifications and accurately measure calcification thickness in comparison with histopathology.

Methods And Results: A total of 902 pathological cross-sections from 44 coronary artery specimens of human cadavers were examined to compare OFDI and histological images. Histological coronary calcification was classified into four different types: (i) superficial dense calcified plates, (ii) deep intimal calcification, (iii) scattered microcalcification, and (iv) calcified nodule. The thickness of calcification was measured when both the leading and trailing edges of calcification were visible on OFDI. Of the 902 histological cross-sections, 158 (18%) had calcification: 105 (66%) were classified as superficial dense calcified plates, 20 (13%) as deep intimal calcifications, 30 (19%) as scattered microcalcifications, and 3 (2%) as calcified nodules. Superficial dense calcified plates appeared as well-delineated heterogeneous signal-poor regions with sharp borders on OFDI. Deep intimal calcifications could not be identified on OFDI. Scattered microcalcification appeared as homogeneous low intensity areas with indiscriminant borders. Calcified nodule, a high-backscattering protruding mass with an irregular surface, also appeared as a low intensity area with a diffuse border. The ROC analysis identified calcium thicknesses <893 µm as cut points for the prediction of measurable calcification (72% sensitivity and 91% specificity, area under the curve = 0.893, P < 0.001).

Conclusion: Our study demonstrated the potential capability of OFDI to characterize various types of coronary calcifications, which may contribute to the understanding of the pathogenesis of coronary atherosclerosis.
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http://dx.doi.org/10.1093/ehjci/jew054DOI Listing
March 2017

Impact of thermodilution-derived coronary blood flow patterns after percutaneous coronary intervention on mid-term left ventricular remodeling in patients with ST elevation myocardial infarction.

Heart Vessels 2017 Jan 5;32(1):1-7. Epub 2016 Apr 5.

Division of Cardiovascular Medicine and Coronary Heart Disease, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

We recently reported the coronary thermodilution curve can be evaluated by analyzing the thermodilution curve obtained from a pressure sensor/thermistor-tipped guidewire, and presence of a bimodal-shaped thermodilution curve following primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients was associated with worse outcomes. This study evaluated whether the bimodal-shaped thermodilution curve predicts left ventricular (LV) remodeling after STEMI. The coronary thermodilution curve patterns were evaluated for 75 patients treated by pPCI for their first STEMI using a pressure sensor/thermistor-tipped guidewire, and classified into the three groups according to the thermodilution curve shape: narrow unimodal (n = 39), wide unimodal (n = 26), and bimodal pattern (n = 10). Echocardiography was performed at baseline and 6 months after STEMI. LV remodeling was defined as a >20 % increase in LV end-diastolic volumes (LVEDV). LVEDV at 6-month follow-up was greater in the bimodal group than in the other groups (p < 0.001). The prevalence of LV remodeling was highest in the bimodal group than in the narrow and wide unimodal groups (60, 12, and 15 %, respectively; p = 0.003). Multivariate analysis revealed a bimodal-shaped thermodilution curve as an independent predictor of the prevalence of LV remodeling. A bimodal-shaped thermodilution curve is associated with LV remodeling after STEMI. This easily assessable coronary thermodilution curve pattern is useful to predict mid-term LV remodeling for STEMI patients at the catheterization laboratory.
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http://dx.doi.org/10.1007/s00380-016-0831-0DOI Listing
January 2017

Intravascular Ultrasound-Derived Stent Dimensions as Predictors of Angiographic Restenosis Following Nitinol Stent Implantation in the Superficial Femoral Artery.

J Endovasc Ther 2016 Jun 4;23(3):424-32. Epub 2016 Apr 4.

Division of Cardiovascular Medicine and Coronary Heart Disease, Hyogo College of Medicine, Nishinomiya, Japan.

Purpose: To identify intravascular ultrasound (IVUS) measurements that can predict angiographic in-stent restenosis (ISR) following nitinol stent implantation in superficial femoral artery (SFA) lesions.

Methods: A retrospective review was conducted of 97 patients (mean age 72.9±8.9 years; 63 men) who underwent IVUS examination during endovascular treatment of 112 de novo SFA lesions between July 2012 and December 2014. Self-expanding bare stents were implanted in 46 lesions and paclitaxel-eluting stents in 39 lesions. Six months after stenting, follow-up angiography was conducted to assess stent patency. The primary endpoint was angiographic ISR determined by quantitative vascular angiography analysis at the 6-month follow-up. Variables associated with restenosis were sought in multivariate analysis; the results are presented as the odds ratio (OR) and 95% confidence interval (CI).

Results: At follow-up, 27 (31.8%) angiographic ISR lesions were recorded. The lesions treated with uncoated stents were more prevalent in the ISR group compared with the no restenosis group (74.1% vs 44.8%, p=0.02). Lesion length was longer (154.4±79.5 vs 109.0±89.3 mm, p=0.03) and postprocedure minimum stent area (MSA) measured by IVUS was smaller (13.9±2.8 vs 16.3±1.6 mm(2), p<0.001) in the ISR group. Multivariate analysis revealed that bare stent use (OR 7.11, 95% CI 1.70 to 29.80, p<0.01) and longer lesion length (OR 1.08, 95% CI 1.01 to 1.16, p=0.04) were predictors of ISR, while increasing postprocedure MSA (OR 0.58, 95% CI 0.41 to 0.82, p<0.01) was associated with lower risk of ISR. Receiver operating characteristic analysis identified a MSA of 15.5 mm(2) as the optimal cutpoint below which the incidence of restenosis increased (area under the curve 0.769).

Conclusion: Postprocedure MSA can predict ISR in SFA lesions, which suggests that adequate stent enlargement during angioplasty might be required for superior patency.
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http://dx.doi.org/10.1177/1526602816641669DOI Listing
June 2016

Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma.

BMC Cancer 2016 Feb 25;16:156. Epub 2016 Feb 25.

Department of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan.

Background: Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.

Methods: We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.

Results: A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4-67.4) and the disease control rate was 85.7 % (60.0-96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6-12.2 months), and median overall survival was 30.0 months (range, 6.2-41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.

Conclusions: S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.
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http://dx.doi.org/10.1186/s12885-016-2159-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766615PMC
February 2016

Ex vivo comparison of angioscopy and histopathology for the evaluation of coronary plaque characteristics.

Int J Cardiovasc Imaging 2016 Jun 12;32(6):863-9. Epub 2016 Feb 12.

Cardiovascular Division/Division of Coronary Heart Disease, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 6638501, Japan.

The yellow plaque has been considered to be a vulnerable and high risk for acute coronary syndrome events but not fully evaluated. The aim of this study was to evaluate the relationship between angioscopic color grade and histological features in coronary autopsy specimens. We longitudinally sectioned 110 coronary arteries from 40 autopsy hearts with non-cardiovascular death. Harvested arteries were imaged with intravascular ultrasound to identify the focal plaque (plaque burden >50 %). An angioscopic examination of each focal plaque evaluated its color intensity as follows: 0 (white), 1 (light yellow), 2 (yellow), or 3 (dark yellow). The corresponding histological assessment was classified according to a modified version of the American Heart Association classification of atherosclerosis. Two hundred six plaques were matched to the histological analysis. Of these, 82 (40 %) were categorized as yellow (≥grade 1). Although, yellow plaque often includes thin-cap fibroatheroma (TCFA), the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for histological TCFA were 83, 91, 22, 99 and 91 %, respectively. The false-positive coronary angioscopic diagnoses for TCFA that contributed to the low positive predictive value consisted of the following plaques: thick FA (>65 μm), accumulations of large quantities of foam cells on the luminal surface, or dense calcified plates at the surface of the intima. Vulnerable coronary plaques were detected with high sensitivity and low positive predictive value from their yellow color on angioscopy. Not only fibroatheroma but also various types of plaques and their components, such as immature lipidic components and superficial calcium plates, appeared yellow on coronary angioscopy.
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http://dx.doi.org/10.1007/s10554-016-0855-7DOI Listing
June 2016

Coronary Angioscopy for the Evaluation of Vessel Response After Drug-Eluting Stent Implantation.

Circ J 2016 4;80(3):590-1. Epub 2016 Feb 4.

Division of Coronary Artery Disease, Department of Internal Medicine, Hyogo College of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-16-0059DOI Listing
August 2016

Neurotoxicity due to prophylactic cranial irradiation for small-cell lung cancer: A retrospective analysis.

Mol Clin Oncol 2015 Sep 11;3(5):1048-1052. Epub 2015 Jun 11.

Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0239, Japan.

Prophylactic cranial irradiation (PCI) is an established part of standard therapy for small-cell lung cancer (SCLC). However, the concerns regarding severe late neurotoxicity following PCI have not yet been systematically investigated. Therefore, the aim of this study was to investigate the neurocognitive functioning of SCLC patients treated with PCI. Limited-disease SCLC (LD-SCLC) patients (n=40) treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (Tokyo, Japan) between January, 2004 and December, 2011 were retrospectively reviewed. A total of 18 LD-SCLC patients were treated with PCI (median age, 65.5 years; range, 52-75 years), whereas 22 LD-SCLC patients did not receive PCI (median age, 65.5 years; range, 57-84 years). The median follow-up for PCI and non-PCI patients was 22 months (range, 4-85 months) and 14.5 months (range, 2-49 months), respectively. Brain metastases occurred in 6 (33%) PCI patients and 11 (50%) non-PCI patients. In the PCI group, dementia occurred in 5 of the 12 PCI patients without brain metastases (42%, 3-40 months after PCI) and in 1 of the 11 non-PCI patients without brain metastases (9%, 4 months after initial treatment). The frequency of dementia in the PCI group was significantly higher compared with that in the non-PCI group (P=0.0357). In the PCI group, all the patients who developed dementia were aged >65 years (range, 66-75 years). Gait disturbance appeared in 25% of the PCI patients without brain metastases (9-27 months after PCI); these patients were also aged >65 years. Patients aged >65 years were significantly more likely to develop dementia (P=0.0028) and gait disturbance (P=0.0291). Therefore, neurotoxicity due to PCI tends to appear more frequently in older patients.
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http://dx.doi.org/10.3892/mco.2015.581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535021PMC
September 2015