Publications by authors named "Shuhei Yoshida"

127 Publications

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J Vasc Surg Cases Innov Tech 2021 Sep 3;7(3):403. Epub 2021 May 3.

Department of Plastic and Reconstructive Surgery, Hiroshima University, Hiroshima, Japan.

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http://dx.doi.org/10.1016/j.jvscit.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261474PMC
September 2021

Investigation of flow velocity in recipient perforator artery for a reliable indicator for the flap transfer with perforator to perforator anastomosis.

Microsurgery 2021 Jul 2. Epub 2021 Jul 2.

Plastic and Reconstructive Surgery, Hiroshima University, Hiroshima, Japan.

Introduction: In flap transfer with perforator to perforator anastomosis (FTPPA), encountering poor pulsation and blood flow in a recipient perforator intraoperatively often makes FTPPA impossible. This study sought to identify color and spectral Doppler ultrasonography (CSDUS) parameters that can aid reliable preoperative selection of a recipient perforator artery.

Patients And Methods: The study enrolled 38 patients with lower extremity lymphedema who underwent vascularized lymphatic tissue transfer with perforator to perforator anastomosis for physiological lymphatic flow reconstruction. In all cases, three candidate recipient perforators were searched in each lower extremities, and vessel diameter and peak systolic flow velocity (PSFV) were measured. The inclusion criteria for candidates were a vessel diameter of >0.5 mm and a PSFV of >10 cm/s. These measures were compared with intraoperative findings, diameters and if there was pulsation and visible spurting evident.

Results: A total of 114 candidates were selected, and 52 of the candidates were dissected until suitable perforators were found. PSFV (cm/s) on CSDUS was ≥20.0 in 32 perforators (84.2%) and was 15.0-19.9 in 6 perforators (15.8%) in the group with pulsation and visible spurting evident, and 15.0-19.9 in one perforator (7.1%) and ≤ 14.9 in 13 perforators (92.9%) in the group without pulsation and visible spurting evident. There was a statistically significant correlation between preoperative PSFV and intraoperative pulsation and visible spurting evident after dissection (P = 0.021 × 10 ). The flap survival rate was 92.1%.

Conclusion: PSFV is an important preoperative determinant of the suitability of a recipient perforator artery for FTPPA.
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http://dx.doi.org/10.1002/micr.30783DOI Listing
July 2021

Predicting recurrence of non-small cell lung cancer based on mean computed tomography value.

J Cardiothorac Surg 2021 May 12;16(1):128. Epub 2021 May 12.

Department of Thoracic Surgery, Kanazawa University School of Medicine, Takara-machi 13-1, Kanazawa, 920-8640, Japan.

Background: The aim of this study was to assess the ability of using mean computed tomography (mCT) values to predict non-small cell lung cancer (NSCLC) tumor recurrence.

Methods: A retrospective study was conducted on 494 patients with stage IA NSCLC. Receiver operating characteristics analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUV to predict tumor recurrence. Multiple logistic regression analyses were performed to determine the independent variables for the prediction of tumor recurrence.

Results: The m-CT values were - 213.7 ± 10.2 Hounsfield Units (HU) for the recurrence group and - 594.1 ± 11.6 HU for the non-recurrence group (p < 0.0001). Recurrence occurred in 45 patients (9.1%). The tumor recurrence group was strongly associated with a high CT attenuation value, high C/T ratio, large solid tumor size, and SUV. The diagnostic value of mCT value was more accurate than the C/T ratio, excluding the pure ground-glass opacity and pure solid (0 < C/T ratio < 100) groups. The SUV and mCT are independent predictive factors of tumor recurrence.

Conclusions: The evaluation of mCT values was useful for predicting recurrence after the limited resection of small-sized NSCLC, and may potentially contribute to the selection of suitable treatment strategies.
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http://dx.doi.org/10.1186/s13019-021-01476-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117299PMC
May 2021

Combined Lymphovenous Anastomosis and Great Saphenous Vein Stripping for Comorbid Lymphedema and Varicose Veins.

Lymphat Res Biol 2021 Mar 31. Epub 2021 Mar 31.

Plastic and Reconstructive Surgery, Tokyo University, Tokyo, Japan.

Treatment for patients with comorbid lymphedema and varicose veins is controversial. Surgical options for these patients are limited. The study was aimed to investigate the validity of combined lymphovenous anastomosis (LVA) and great saphenous vein stripping (GSVS) for comorbid lymphedema and varicose veins. Thirteen patients were involved in the study, and the detail was 21 edematous lower limbs (with coexisting varicose veins and lymphedema; the varicose vein and lymphedema [VL] group) who underwent combined GSVS and LVA therapy. Fifteen patients (with 30 edematous lower limbs and lymphedema only; the lymphedema [L] group) who underwent LVA only were included as a control group. GSVS was performed before LVA in the VL group. No significant differences were seen between the groups at baseline. There were no cases indocyanine green (ICG) lymphography pattern deteriorated after GSVS. No significant difference was seen in lymphatic detection rate; 129.71% ± 58.27% (67%-333%) in the VL group and 122.27% ± 39.47% (50%-250%) in the L group ( = 0.59 > 0.05), respective lymphatic diameters 0.66 ± 0.13 (0.45-0.9) mm and 0.75 ± 0.17 (0.45-1.0) mm ( = 0.07 > 0.05), and respective lymphedema improvement rate 12.17% ± 7.35% (0%-27.4%) and 12.65% ± 7.43% (3.7%-22.3%) ( = 0.86 > 0.05). In this study, stripping surgery does not cause lymphatic impairment, at least to the extent that would impede the success of an LVA procedure. Comorbid varicose veins and lymphedema can be treated surgically by a combination of LVA and GSVS.
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http://dx.doi.org/10.1089/lrb.2019.0076DOI Listing
March 2021

Attenuation correction using deep learning for brain perfusion SPECT images.

Ann Nucl Med 2021 May 9;35(5):589-599. Epub 2021 Mar 9.

Division of Positron Emission Tomography, Institute of Advanced Clinical Medicine, Kindai University, Osaka, 589-8511, Japan.

Objective: Non-uniform attenuation correction using computed tomography (CT) improves the image quality and quantification of single-photon emission computed tomography (SPECT). However, it is not widely used because it requires a SPECT/CT scanner. This study constructs a convolutional neural network (CNN) to generate attenuation-corrected SPECT images directly from non-attenuation-corrected SPECT images.

Methods: We constructed an auto-encoder (AE) using a CNN to correct the attenuation in brain perfusion SPECT images. SPECT image datasets of 270 (44,528 slices including augmentation), 60 (5002 slices), and 30 (2558 slices) cases were used for training, validation, and testing, respectively. The acquired projection data were reconstructed in three patterns: uniform attenuation correction using Chang's method (Chang-AC), non-uniform attenuation correction using CT (CT-AC), and no attenuation correction (No-AC). The AE learned an end-to-end mapping between the No-AC and CT-AC images. The No-AC images in the test dataset were loaded into the trained AE, which generated images simulating the CT-AC images as output. The generated SPECT images were employed as attenuation-corrected images using the AE (AE-AC). The accuracy of the AE-AC images was evaluated in terms of the peak signal-to-noise ratio (PSNR) and the structural similarity metric (SSIM). The intensities of the AE-AC and CT-AC images were compared by voxel-by-voxel and region-by-region analysis.

Results: The PSNRs of the AE-AC and Chang-AC images, compared using CT-AC images, were 62.2, and 57.9, and their SSIM values were 0.9995 and 0.9985, respectively. The AE-AC and CT-AC images were visually and statistically in good agreement.

Conclusions: The proposed AE-AC method yields highly accurate attenuation-corrected brain perfusion SPECT images.
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http://dx.doi.org/10.1007/s12149-021-01600-zDOI Listing
May 2021

Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective β-Secretase (BACE1) Inhibitors over BACE2.

J Med Chem 2021 03 15;64(6):3075-3085. Epub 2021 Mar 15.

Laboratory for Medicinal Chemistry Research, Shionogi Pharmaceutical Research Center, 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.

BACE1 is an attractive target for disease-modifying treatment of Alzheimer's disease. BACE2, having high homology around the catalytic site, poses a critical challenge to identifying selective BACE1 inhibitors. Recent evidence indicated that BACE2 has various roles in peripheral tissues and the brain, and therefore, the chronic use of nonselective inhibitors may cause side effects derived from BACE2 inhibition. Crystallographic analysis of the nonselective inhibitor verubecestat identified explicit water molecules with different levels of free energy in the S2' pocket. Structure-based design targeting them enabled the identification of propynyl oxazine with improved selectivity. Further optimization efforts led to the discovery of compound with high selectivity. The cocrystal structures of , a close analogue of , bound to BACE1 and BACE2 confirmed that one of the explicit water molecules is displaced by the propynyl group, suggesting that the difference in the relative water displacement cost may contribute to the improved selectivity.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01858DOI Listing
March 2021

Stable kinetochore-microtubule attachments restrict MTOC position and spindle elongation in oocytes.

EMBO Rep 2021 04 3;22(4):e51400. Epub 2021 Mar 3.

Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.

In mouse oocytes, acentriolar MTOCs functionally replace centrosomes and act as microtubule nucleation sites. Microtubules nucleated from MTOCs initially assemble into an unorganized ball-like structure, which then transforms into a bipolar spindle carrying MTOCs at its poles, a process called spindle bipolarization. In mouse oocytes, spindle bipolarization is promoted by kinetochores but the mechanism by which kinetochore-microtubule attachments contribute to spindle bipolarity remains unclear. This study demonstrates that the stability of kinetochore-microtubule attachment is essential for confining MTOC positions at the spindle poles and for limiting spindle elongation. MTOC sorting is gradual and continues even in the metaphase spindle. When stable kinetochore-microtubule attachments are disrupted, the spindle is unable to restrict MTOCs at its poles and fails to terminate its elongation. Stable kinetochore fibers are directly connected to MTOCs and to the spindle poles. These findings suggest a role for stable kinetochore-microtubule attachments in fine-tuning acentrosomal spindle bipolarity.
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http://dx.doi.org/10.15252/embr.202051400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024892PMC
April 2021

Modified intraoperative distal compression method for lymphaticovenous anastomosis with high success and a low venous reflux rates.

J Plast Reconstr Aesthet Surg 2021 Jan 14. Epub 2021 Jan 14.

Plastic and Reconstructive Surgery, The University of Tokyo, Japan.

Introduction: For successful lymphaticovenous anastomosis (LVA), it is important to create anastomoses with high flow to maintain patency. To ensure that this can be achieved, we compared the efficacy of a modified intraoperative distal compression (IDC) technique with the conventional no compression (NC) method for lower limb lymphedema.

Patients And Methods: In the IDC group, compression was applied to an area of the foot distal to the first LVA site. After completion of the first LVA, the distal compression was extended over the first LVA site to the distal end of the second LVA site.

Results: There was no significant difference between the IDC (n = 25) and NC (n = 25) groups in detection rate. However, significant differences were observed in lymphatic vessel diameter and LVA success rate. No intraoperative anastomotic obstruction was seen at the conclusion of surgery. Intraoperative congestion with blood was detected in lymphatic vessels in 8 of 79 anastomoses (10.1%) in the NC group, but not in any cases in the IDC group (p = 0.002). There was a significant between-group difference in the rate of improvement in lymphedema between the IDC (16.1±3.6) and NC groups (14.0±3.4; p = 0.03).

Discussion: IDC during LVA is thought to increase lymph flow in larger caliber lymphatics, leading to a high success rate and a low rate of venous reflux. IDC is beneficial when performing LVA.
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http://dx.doi.org/10.1016/j.bjps.2020.12.103DOI Listing
January 2021

Intracellular mineralization of gold nanoparticles using gold ion-binding peptides with cell-penetrating ability.

Chem Commun (Camb) 2021 Jan;57(6):725-728

Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 6500047, Kobe, Japan.

We developed a system to directly produce gold nanoparticles in cells by intracellular mineralization in lower concentration than conventional methods using a peptide consisting of a cell-penetrating sequence and a gold ion-binding sequence. Furthermore, we could control the uniquely shaped gold nanostructures that were produced by changing peptide structures.
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http://dx.doi.org/10.1039/d0cc06117dDOI Listing
January 2021

DNA maintenance methylation enzyme Dnmt1 in satellite cells is essential for muscle regeneration.

Biochem Biophys Res Commun 2021 01 10;534:79-85. Epub 2020 Dec 10.

Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Shitsukawa, Toon Ehime, 791-0295, Japan; Department of Pathophysiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon Ehime, 791-0295, Japan; Division of Laboratory Animal Research, Advanced Research Support Center, Ehime University, Shitsukawa, Toon Ehime, 791-0295, Japan. Electronic address:

Epigenetic transcriptional regulation is essential for the differentiation of various types of cells, including skeletal muscle cells. DNA methyltransferase 1 (Dnmt1) is responsible for maintenance of DNA methylation patterns via cell division. Here, we investigated the relationship between Dnmt1 and skeletal muscle regeneration. We found that Dnmt1 is upregulated in muscles during regeneration. To assess the role of Dnmt1 in satellite cells during regeneration, we performed conditional knockout (cKO) of Dnmt1 specifically in skeletal muscle satellite cells using Pax7 mice and Dnmt1 flox mice. Muscle weight and the cross-sectional area after injury were significantly lower in Dnmt1 cKO mice than in control mice. RNA sequencing analysis revealed upregulation of genes involved in cell adhesion and apoptosis in satellite cells from cKO mice. Moreover, satellite cells cultured from cKO mice exhibited a reduced number of cells. These results suggest that Dnmt1 is an essential factor for muscle regeneration and is involved in positive regulation of satellite cell number.
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http://dx.doi.org/10.1016/j.bbrc.2020.11.116DOI Listing
January 2021

Development and validation of a Japanese version of the Patient Centred Assessment Method and its user guide: a cross-sectional study.

BMJ Open 2020 11 24;10(11):e037282. Epub 2020 Nov 24.

Division of Clinical Epidemiology, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan

Objectives: The primary objective of this study was to develop the Japanese version of the Patient Centred Assessment Method (PCAM) and its user guide. The secondary objective was to examine the validity and reliability in the primary care setting.

Design: Cross-sectional study.

Setting: Three family physician teaching clinics located in urban residential areas in Tokyo, Japan.

Participants: Patients who were aged 20 years or older, and who had an appointment with physicians at the three participating clinics.

Main Outcome Measures: Patient complexity measured by PCAM and complexity/burden level measured by a Visual Analogue Scale (VAS).

Results: Although confirmatory factor analysis using a model described in a previous study revealed that the indices did not meet the criteria for good fit, exploratory factor analysis revealed a new three-factor structure of 'Personal well-being,' 'Social interaction' and 'Needs for care/service.' Cronbach's alpha of PCAM was 0.86. Spearman's rank correlation coefficients between PCAM scores and VAS scores were 0.51 for complexity (p<0.001) and 0.41 for burden (p<0.001). There were 42 patients (14.3% of total patients) with PCAM scores greater than its mean of 16.5 but with complexity VAS scores less than its mean of 20.8.

Conclusions: The Japanese version of PCAM and its user guide were developed through Japanese translation and cultural adaptation by cognitive debriefing. PCAM is a valid and reliable tool to assess patient complexity in the primary care settings in Japan. Additionally, although the correlation between total PCAM scores and complexity/burden as assessed by VAS was moderate, PCAM can more precisely identify patient complexity than skilled physician's intuition.
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http://dx.doi.org/10.1136/bmjopen-2020-037282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689105PMC
November 2020

Lymphovenous Anastomosis for Morbidly Obese Patients with Lymphedema.

Plast Reconstr Surg Glob Open 2020 May 27;8(5):e2860. Epub 2020 May 27.

Plastic and Reconstructive Surgery, Tokyo University, Tokyo, Japan.

Although patients with obesity-induced lymphedema can be treated by weight loss therapy, they find it difficult to lose the required amount of weight. The aims of this study were to clarify the characteristics of the lymphatic vessels in patients with obesity-induced lymphedema and to determine the feasibility and efficacy of lymphovenous anastomosis (LVA) in these patients.

Methods: Twenty-two patients (44 edematous lower limbs) with a body mass index (BMI) >35 kg/m (obese group) and 91 patients with lymphedema (141 edematous lower limbs) and BMI <25 kg/m were enrolled as a control group (nonobese group) and underwent LVA. The diameter and depth of lymphatics and the effect of LVA were compared.

Results: Lymphatics were detectable within 10-mm depth in the nonobese group and the obese group (3.0 ± 1.4 mm versus 3.5 ± 2.1 mm; < 0.01). The lymphatic diameter was significantly greater in the obese group than in the nonobese group (0.79 ± 0.30 mm versus 0.54 ± 0.22 mm; < 0.01). There was no significant difference in the rate of improvement in lymphedema after LVA between the nonobese group (9.1% ± 9.2%) and the obese group (8.9% ± 7.3%; = 0.84). There was no correlation between the improvement rate of lymphedema and that of BMI in the obese group ( = 0.57).

Conclusions: LVA is a feasible procedure even in morbidly obese patients. Considering that substantial weight loss is a difficult and time-consuming task for patients, LVA combined with not gaining weight is a good option for these patients.
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http://dx.doi.org/10.1097/GOX.0000000000002860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572113PMC
May 2020

Lymphaticovenous Anastomosis in Fowler's Position under Local Anesthesia.

Plast Reconstr Surg Glob Open 2020 Aug 17;8(8):e3067. Epub 2020 Aug 17.

Department of Plastic and Reconstructive Surgery, Hiroshima University, Hiroshima, Japan.

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http://dx.doi.org/10.1097/GOX.0000000000003067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489648PMC
August 2020

A method to identify pulmonary intersegmental planes with intravenous vitamin B injection.

Surg Today 2021 May 14;51(5):836-843. Epub 2020 Sep 14.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

Purpose: The present study investigated whether the pulmonary intersegmental planes could be identified with the intravenous injection of vitamin B using a fluorescent camera and whether this method can be used instead of the inflation-deflation technique or the intravenous indocyanine green (ICG) method.

Methods: In experiment 1, the vitamin B was intravenously injected to visualize the pulmonary intersegmental plane and perform segmentectomy, and the visualized pulmonary intersegmental line was then compared to the inflation-deflation line in six pigs. In experiment 2, using six pigs, the fluorescent area and duration of fluorescence were compared after the intravenous injection of vitamin B and ICG in the same animals.

Results: In all animals in experiment 1, it was possible to clearly detect yellow-green fluorescence in the lung, in segments other than the one intended for resection, for at least 60 min. Moreover, the line visualized with vitamin B fluorescence matched the inflation-deflation line in all animals. In experiment 2, the area of vitamin B fluorescence corresponded to the area of ICG fluorescence in each animal.

Conclusions: The visualization of fluorescence after the intravenous injection of vitamin B using a fluorescent camera was a simple, safe, and accurate method for detecting intersegmental planes in a pig model. This method can be an alternative to the inflation-deflation technique and the intravenous ICG method.
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http://dx.doi.org/10.1007/s00595-020-02137-wDOI Listing
May 2021

Cdk1 negatively regulates the spindle localization of Prc1 in mouse oocytes.

Genes Cells 2020 Oct 21;25(10):685-694. Epub 2020 Sep 21.

Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.

Chromosome segregation requires the formation of a bipolar spindle. The timely bipolarization of the acentrosomal spindle during meiosis I in mouse oocytes depends on the antiparallel microtubule crosslinker Prc1. How Prc1 is regulated in oocytes remains poorly understood. In this study, we show that the kinase Cdk1 negatively regulates the spindle localization of Prc1 in mouse oocytes. The acute inhibition of Cdk1 activity led to excessive localization of Prc1 at the spindle and kinetochores, whereas the overactivation of Cdk1 had opposite effects. The overexpression of Prc1 carrying mutations at Cdk1-mediated phosphorylation sites increased its localization to the spindle, accelerated spindle bipolarization and caused spindle-checkpoint-dependent arrest at metaphase I. Overactivation of Cdk1 delayed spindle bipolarization, which was reversed by the overexpression of a phospho-mutant form but not the wild-type form of Prc1. These results suggest that Cdk1-mediated phosphorylation negatively regulates Prc1 localization to ensure the timely bipolarization of the acentrosomal spindle during meiosis I in mammalian oocytes.
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http://dx.doi.org/10.1111/gtc.12803DOI Listing
October 2020

Simple Method for Deep Insertion of Drainage Tube through a Small Skin Incision.

Plast Reconstr Surg Glob Open 2020 Jul 8;8(7):e2951. Epub 2020 Jul 8.

Plastic and Reconstructive Surgery, Hiroshima University, Hiroshima, Japan.

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http://dx.doi.org/10.1097/GOX.0000000000002951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413790PMC
July 2020

Lymphaticovenular anastomosis for recurrent cellulitis in a dementia patient with lymphedema.

J Vasc Surg Cases Innov Tech 2020 Sep 25;6(3):340-343. Epub 2020 Jun 25.

Department of Plastic and Reconstructive Surgery, Hiroshima University, Hiroshima, Japan.

We describe a dementia patient with comorbid recurrent cellulitis and lymphedema in the left lower limb who was treated successfully for recurrent cellulitis by lymphaticovenular anastomosis (LVA). The patient, an 83-year-old woman, suffered from recurrent cellulitis three times a year on average for 15 years. Compression therapy was impossible because of dementia. After LVA, there has been no recurrence of cellulitis for 2 years. It is difficult to administer decongestive lymphatic therapy in some patients, such as patients with dementia. LVA is a promising treatment for recurrent cellulitis in a dementia patient with lymphedema.
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http://dx.doi.org/10.1016/j.jvscit.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371726PMC
September 2020

Case report: uniportal video-assisted thoracoscopic resection of a solitary fibrous tumor preoperatively predicted visceral pleura origin using dynamic chest radiography.

J Cardiothorac Surg 2020 Jul 8;15(1):166. Epub 2020 Jul 8.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Takara-machi 13-1, Kanazawa, 920-8640, Japan.

Background: Dynamic chest radiography (DCR) is a flat-panel detector (FPD)-based functional X-ray imaging, which is performed as an additional examination in chest radiography. DCR provides objective and quantifiable information, such as diaphragm movement, pulmonary ventilation and circulation, and is reasonable for detecting tumor invasion or adhesion.

Case Presentation: We present a case of Solitary Fibrous Tumor of Pleura (SFTP), preoperatively predicted visceral pleura origin using Dynamic chest radiography (DCR) and surgically resected through single-access (uniportal) video-assisted thoracoscopic surgery (UVATS).

Conclusions: UVATS may be a suitable surgical option for pedunculated SFTPs. Dynamic chest radiography provides information, such as tumor invasion or adhesion and helpful for predicting origin of the tumor.
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http://dx.doi.org/10.1186/s13019-020-01212-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346465PMC
July 2020

Semi-comprehensive analysis of gene amplification in thymic malignant tumors using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization.

Int J Clin Exp Pathol 2020 1;13(5):1035-1044. Epub 2020 May 1.

Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University Ishikawa, Japan.

Research on the amplification of oncogenes in thymic malignant tumor is limited. In this study, we aimed to determine the gene amplification status of receptor tyrosine kinases and other cell regulator genes in thymic malignant tumors, with a view toward the future introduction of molecular targeted therapy. In addition, we examined the usefulness of multiplex, ligation-dependent probe amplification (MLPA) in the semi-comprehensive detection of these gene amplifications. The participants of this study were nine patients with thymic carcinoma and one patient with atypical carcinoid who underwent resection at our department from 1999 to 2016. Twenty-four oncogenes () were analyzed for amplification by MLPA. In cases where amplification by MLPA was suspected, confirmation was performed by fluorescence in situ hybridization (FISH). Immunostaining for detected oncoproteins and p53 were performed in cases with confirmed oncogene amplification. (2/10, 20%) and (1/10, 10%) amplifications were detected using MLPA and FISH. Immunostaining in both cases was positive. The -amplified tumor relapsed and spread rapidly after operation despite the use of post-operative chemo-radiotherapy. amplification may be involved in the carcinogenesis of thymic malignant tumors. In addition, amplification may be a concern in the increased malignancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270679PMC
May 2020

Prc1-rich kinetochores are required for error-free acentrosomal spindle bipolarization during meiosis I in mouse oocytes.

Nat Commun 2020 05 27;11(1):2652. Epub 2020 May 27.

Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, 650-0047, Japan.

Acentrosomal meiosis in oocytes represents a gametogenic challenge, requiring spindle bipolarization without predefined bipolar cues. While much is known about the structures that promote acentrosomal microtubule nucleation, less is known about the structures that mediate spindle bipolarization in mammalian oocytes. Here, we show that in mouse oocytes, kinetochores are required for spindle bipolarization in meiosis I. This process is promoted by oocyte-specific, microtubule-independent enrichment of the antiparallel microtubule crosslinker Prc1 at kinetochores via the Ndc80 complex. In contrast, in meiosis II, cytoplasm that contains upregulated factors including Prc1 supports kinetochore-independent pathways for spindle bipolarization. The kinetochore-dependent mode of spindle bipolarization is required for meiosis I to prevent chromosome segregation errors. Human oocytes, where spindle bipolarization is reportedly error prone, exhibit no detectable kinetochore enrichment of Prc1. This study reveals an oocyte-specific function of kinetochores in acentrosomal spindle bipolarization in mice, and provides insights into the error-prone nature of human oocytes.
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http://dx.doi.org/10.1038/s41467-020-16488-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253481PMC
May 2020

Yield strength and misfit volumes of NiCoCr and implications for short-range-order.

Nat Commun 2020 05 19;11(1):2507. Epub 2020 May 19.

Laboratory for Multiscale Mechanics Modeling (LAMMM) and National Centre for Computational Design and Discovery of Novel Materials (NCCR MARVEL), École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.

The face-centered cubic medium-entropy alloy NiCoCr has received considerable attention for its good mechanical properties, uncertain stacking fault energy, etc, some of which have been attributed to chemical short-range order (SRO). Here, we examine the yield strength and misfit volumes of NiCoCr to determine whether SRO has measurably influenced mechanical properties. Polycrystalline strengths show no systematic trend with different processing conditions. Measured misfit volumes in NiCoCr are consistent with those in random binaries. Yield strength prediction of a random NiCoCr alloy matches well with experiments. Finally, we show that standard spin-polarized density functional theory (DFT) calculations of misfit volumes are not accurate for NiCoCr. This implies that DFT may be inaccurate for other subtle structural quantities such as atom-atom bond distance so that caution is required in drawing conclusions about NiCoCr based on DFT. These findings all lead to the conclusion that, under typical processing conditions, SRO in NiCoCr is either negligible or has no systematic measurable effect on strength.
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http://dx.doi.org/10.1038/s41467-020-16083-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237450PMC
May 2020

[Surgical Treatment of Pectus Excavatum in Patients with Marfan Syndrome Associated with Vertebral or Cardiovascular Disease].

Kyobu Geka 2020 Mar;73(3):163-168

Department of General, Thoracic and Cardiovascular Surgery, Kanazawa University, Kanazawa, Japan.

Surgical treatment is often required in patients with Marfan syndrome presenting with scoliosis or cardioaortic disease. If these patients present with pectus excavatum, surgery for spinal deformity correction or chest wall closure during cardioaortic surgery can cause thoracic organ compression secondary to narrowing of the thorax resulting in hemodynamic and respiratory compromise. Cardiovascular complications serve as prognostic factors in patients with Marfan syndrome, and surgical treatment is often required in these cases. In our case series involving 4 patients, 2 patients with pectus excavatum and scoliosis underwent a Nuss procedure followed by safe and successful spinal correction surgery 6 months later. A Nuss procedure was also performed in a patient complicated with sinus of Valsalva dilatation, and thoracotomy was performed before cardioaortic surgery. Another patient with a complication of pectus excavatum and acute deterioration of cardiac status underwent concomitant repair with sternal elevation using an AO plate and cardioaortic surgery. In patients with Marfan syndrome presenting with pectus excavatum complicated by scoliosis or cardioaortic disease, it is necessary to consider concomitant or staged repair depending on the disease condition.
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March 2020

Dynamic chest radiography: Novel and less-invasive imaging approach for preoperative assessments of pleural invasion and adhesion.

Radiol Case Rep 2020 Jun 6;15(6):702-704. Epub 2020 Apr 6.

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Here, we report a case of lung cancer with preoperatively predicted invasion to the parietal pleura on dynamic chest radiography (DCR). An 82-year-old patient was referred for staging of a right lung tumor. Preoperative DCR revealed invasion or adhesion of the tumor to the chest wall, and intraoperative findings revealed invasion of the tumor to the parietal pleura. DCR provides objective and quantifiable information, including diaphragmatic movement, pulmonary ventilation, and circulation, as well as tumor invasion or adhesion and is less invasive compared to 3-dimensional chest computed tomography or cine magnetic resonance imaging. This study was our initial attempt at performing a quantitative assessment using DCR.
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http://dx.doi.org/10.1016/j.radcr.2020.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138928PMC
June 2020

Vitamin B2 lung-marking method using black light irradiation.

J Thorac Dis 2020 Mar;12(3):651-658

Department of Thoracic, Cardiovascular and General Surgery, Kanazawa University, Kanazawa, Japan.

Background: Various approaches and markers for marking the lungs prior to lung tumor resection have been reported. In clinical practice, the hook wire localization method is often used owing to the simplicity of the technique. However, although rare, this method is associated with air embolism, which can be lethal. Because vitamin B2 is harmless to the body and fluorescent, it was applied to various methods for thoracic surgery. Using a pig model, we aimed to examine whether a lung-marking method involving the injection of vitamin B2 to peripheral small lung lesions and observing them under black light irradiation could replace the hook wire localization method.

Methods: We used a pig model to perform hook wire localization of the lungs and at the same time injected 1 mL of a vitamin B2 aqueous solution to the lung parenchyma at the hook wire puncture site under the visceral pleura. Subsequently, we measured the length of the fluorescent marked area and fluorescence intensity over time. Black light was used to assess the fluorescent marked area, and fluorescence intensity was quantified using image analysis software.

Results: Lung-marking was successful in all five pigs and we visualized the vitamin B2-marked area under black light irradiation. Measurements were taken immediately after thoracotomy (0 min) and 60 and 120 min thereafter. No changes in the length of the marked area (1.3±0.3/1.2±0.3/1.1±0.3 cm, 0/60/120 min, P=0.21) and fluorescence intensity (162.8±55.1/157.2±63.1/165.2±62.2, 0/60/120 min, P=0.96) were observed over time. Compared to the non-marked area (normal lungs), the marked area showed significantly higher fluorescence intensity (P=0.01/0.01/0.01, 0/60/120 min).

Conclusions: Vitamin B2 lung-marking was performed safely and accurately using the pig model, providing good visibility of the marked area. This approach may replace the hook wire localization method. In the near future, we plan to conduct clinical trials to evaluate the applicability of this method in humans.
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http://dx.doi.org/10.21037/jtd.2020.01.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139060PMC
March 2020

Reoperation with laparoscopic mesh repair for recurrent lumbar hernia due to iliac crest bone harvest.

Asian J Endosc Surg 2021 Jan 23;14(1):136-139. Epub 2020 Mar 23.

Department of Thoracic, Cardiovascular, and General Surgery, Kanazawa University, Kanazawa, Japan.

Previous reports have described laparoscopic mesh repair for lumbar hernia due to iliac crest bone harvest, but there have been no reports of reoperation with laparoscopic mesh repair for recurrent cases after laparoscopic mesh repair. Here, we describe the case of a 72-year-old Japanese woman with lumbar hernia recurrence 6 years after laparoscopic mesh repair for lumbar hernia due to iliac crest bone harvest. We performed a successful reoperation with laparoscopic mesh repair. Laparoscopic surgery should be considered to elucidate the mechanism of recurrence, previous mesh position, and the area that must be covered to prevent recurrence again.
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http://dx.doi.org/10.1111/ases.12798DOI Listing
January 2021

Role of lymphatico venular anastomosis for treatment of lymphorrhea in lower limbs.

J Plast Reconstr Aesthet Surg 2020 07 18;73(7):1357-1404. Epub 2020 Feb 18.

Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.bjps.2020.02.029DOI Listing
July 2020

Microscope-Induced Thermal Burns During Lymphaticovenular Anastomosis.

Ann Plast Surg 2020 05;84(5):e24-e26

Plastic and Reconstructive Surgery, Tokyo University, Tokyo, Japan.

Bright illumination sources using xenon lamps have improved microsurgical visualization under an operating microscope; however, surgeons must recognize the potential for accidental thermal damage to soft tissues.In this article, we present 2 reports of microscopic thermal burn in lymphaticovenular anastomosis (LVA).A 23-year-old woman and a 57-year-old woman with bilateral lymphedema of the legs had LVAs on both legs under local anesthesia. The burn wound in a 23-year-old woman was full thickness, and the one in a 57-year-old woman was deep dermal burn. Both of them healed without skin grafting.Working distance and high illumination intensity are important risk factor. The use of epinephrine as part the local anesthetic mixture that decreases blood flow is also a major risk factor for thermal burns. Lymphaticovenular anastomosis particularly requires high magnification, which leads to increasing the intensity and decreasing the working distance. The surgical conditions around LVA are inherently prone to microscope-induced thermal burns.
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http://dx.doi.org/10.1097/SAP.0000000000002116DOI Listing
May 2020

Characteristics and outcomes of lymphaticovenular anastomosis in older patients with bilateral involvement versus younger patients with unilateral involvement in lower extremity lymphedema.

J Vasc Surg Venous Lymphat Disord 2020 07 14;8(4):646-657. Epub 2019 Dec 14.

Department of Plastic and Reconstructive Surgery, Jichi Medical University, Tochigi, Japan.

Objective: We have previously reported that patients with idiopathic primary lymphedema of adult onset can be classified into an older group with bilateral involvement and a younger group with unilateral involvement and that there are significant differences in the characteristics of these groups. The aims of this study were to investigate the features of these two groups further by evaluating the lymphatics while performing lymphaticovenular anastomosis (LVA) and to compare the effectiveness of LVA between the two groups.

Methods: This study enrolled 74 patients (136 edematous legs) in whom indocyanine green (ICG) lymphography and LVA were performed. The rate of detection and the diameter of the lymphatic vessels were recorded. The lower extremity lymphedema index (the total sum of the squares of the circumference for five areas in each leg divided by the body mass index) was obtained before and 6 months after LVA. The rate of improvement in the affected lower limbs after LVA was also calculated.

Results: The clinical lymphedema pattern was determined to be bilateral in 62 patients and unilateral in 12. Patients with bilateral lymphedema were significantly older than those with unilateral lymphedema (77.1 ± 7.8 years vs 55.5 ± 12.77 years; P < .01). A linear pattern was seen in 23 patients (46 legs), a low enhancement (LE) pattern in 12 patients (24 legs), a distal dermal backflow (dDB) pattern in 20 patients (40 legs), and an extended dermal backflow (eDB) pattern in 7 patients (14 legs). The lymphedema was unilateral in 12 patients (12 legs). There were significant between-group differences in lymphatic diameter in relation to lower leg area: linear (0.9 ± 0.1 mm) vs dDB (0.7 ± 0.2 mm), linear vs eDB (0.7 ± 0.2 mm), linear vs unilateral (0.5 ± 0.1 mm), LE (0.9 ± 0.2 mm) vs dDB, LE vs eDB, LE vs unilateral, and dDB vs unilateral, P < .01; and eDB vs unilateral, P < .05. There were also significant between-group differences in the rate of improvement in the lower extremity lymphedema index according to the ICG lymphography pattern and laterality: linear (10.5% ± 2.4%) vs unilateral (6.7% ± 0.6%), LE (10.4% ± 1.5%) vs unilateral, dDB (11.0% ± 1.3%) vs eDB (8.9% ± 1.5%), and dDB vs unilateral, P < .01; linear vs eDB, P < .05; and eDB vs unilateral, P < .05.

Conclusions: The lymphatic vessel diameter tended to be greater in older patients with bilateral lymphedema than in younger patients with unilateral lymphedema. The rate of detection and improvement tended to decrease with worsening of the ICG lymphography pattern. LVA is thought to be more effective in older patients with early-stage bilateral lower leg lymphedema than in their younger counterparts with late-stage unilateral lymphedema.
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http://dx.doi.org/10.1016/j.jvsv.2019.10.013DOI Listing
July 2020

Lymphovenous Anastomosis Aids Wound Healing in Lymphedema: Relationship Between Lymphedema and Delayed Wound Healing from a View of Immune Mechanisms.

Adv Wound Care (New Rochelle) 2019 Jun 6;8(6):263-269. Epub 2019 Jun 6.

Plastic and Reconstructive Surgery, Tokyo University, Tokyo, Japan.

Delayed wound healing in lymphedema is assumed to be caused by two reasons, pathophysiological and immunological effects of lymphedema. The aim of this review is to establish how impaired lymphatics alter wound healing pathophysiologically and immunologically, and to propose treatment modalities that can promote wound healing in lymphedema. Lymphaticovenular anastomoses (lymphovenous anastomoses [LVAs]) were performed on patients who had recurrent cellulitis several times with lymphorrhea and developed severe ulcers that were refractory to skin grafts, flaps, and conservative therapy. The lymphorrhea and the ulcer had healed by 4 weeks. Moreover, the lymphedema improved without compression therapy. Lymphedema is characterized pathophysiologically by localized peripheral edema that compresses the microvasculature and lymphatic vasculature and impairs tissue remodeling. Another suspected mechanism is an imbalance in the differentiation of participating immune cells. Profound suppression of T helper (Th)1 cells is likely to increase the risk of infection, and excessive differentiation of Th2 cells, including M2 macrophage polarization, may promote fibrosis, which disrupts the carefully orchestrated wound healing process. Although negative-pressure wound therapy is useful for the treatment of delayed wound healing in lymphedema, LVAs may be necessary to treat the fundamental problem of lymphedema. LVAs are considered to create a bypass to the lymph nodes through which dendritic cells (DCs) can transmit antigen information to T cells. LVAs are considered to neutralize chronic inflammation by allowing more DCs to return into the circulation, thereby improving wound healing.
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http://dx.doi.org/10.1089/wound.2018.0871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906758PMC
June 2019

Geographical distribution of family physicians in Japan: a nationwide cross-sectional study.

BMC Fam Pract 2019 10 29;20(1):147. Epub 2019 Oct 29.

Department of Community Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.

Background: Geographical maldistribution of physicians, and their subsequent shortage in rural areas, has been a serious problem in Japan and in other countries. Family Medicine, a new board-certified specialty started 10 years ago in Japan by Japan Primary Care Association (JPCA), may be a solution to this problem.

Methods: We obtained the workplace information of 527 (78.4%) of the 672 JPCA-certified family physicians from an online database. From the national census data, we also obtained the workplace information of board-certified general internists, surgeons, obstetricians/gynaecologists and paediatricians and of all physicians as the same-generation comparison group (ages 30 to 49). Chi-squared test and residual analysis were conducted to compare the distribution between family physicians and other specialists.

Results: Five hundred nineteen JPCA-certified family physicians and 137,587 same-generation physicians were analysed. The distribution of family physicians was skewed to municipalities with a lower population density, which shows a sharp contrast to the urban-biased distribution of other specialists. The proportion of family physicians in non-metropolitan municipalities was significantly higher than that expected based on the distribution of all same-generation physicians (p < 0.001).

Conclusions: Family physicians distributed in favour of rural areas much more than any other specialists in Japan. The better balance of family physician distribution reported from countries with a strong primary care orientation seems to hold even in a country where primary care orientation is weak, physician distribution is not regulated, and patients have free access to healthcare. Family physicians comprise only 0.2% of all Japanese physicians. However, if their population grows, they can potentially rectify the imbalance of physician distribution. Government support is mandatory to promote family medicine in Japan.
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http://dx.doi.org/10.1186/s12875-019-1040-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819408PMC
October 2019
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