Publications by authors named "Masaaki Sato"

338 Publications

Pediatric living-donor lobar lung transplantation in postpneumonectomy-like anatomy caused by pulmonary hypoplasia with congenital diaphragmatic hernia.

Am J Transplant 2021 May 2. Epub 2021 May 2.

Department of Thoracic Surgery, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

When performing living-donor lobar lung transplantation on small children of height 100 cm or under, accommodation of an oversized adult lobar graft is problematic, sometimes necessitating single lobar transplantation in combination with contralateral pneumonectomy. We here report a unique case of living-donor lobar lung transplantation in a 9-year-old boy with congenital pulmonary hypoplasia. Although he was 104 cm tall, and the available adult lower lobe graft appeared to be oversized, his right lung was hypoplastic, resulting in his mediastinum being shifted to the right and thus already showing "postpneumonectomy-like" anatomy. His father's left lower lobe was successfully transplanted into the left thorax without performing a contralateral pneumonectomy. Three-dimensional reconstruction of computed tomography images and computed tomography volumetry were extremely helpful in matching the size of the graft and planning this unique surgery.
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http://dx.doi.org/10.1111/ajt.16626DOI Listing
May 2021

Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers.

Am J Physiol Cell Physiol 2021 Apr 21. Epub 2021 Apr 21.

Division of Bioengineering, Graduate School of Engineering Science, Osaka University, Japan.

Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here we suggest that the mechanosensitive behavior of myosin II, a major cross-linker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.
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http://dx.doi.org/10.1152/ajpcell.00225.2020DOI Listing
April 2021

GPR55 regulates the responsiveness to, but does not dimerise with, α-adrenoceptors.

Biochem Pharmacol 2021 May 1;188:114560. Epub 2021 May 1.

Cardiometabolic Health Research, School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Aberdeen AB10 7GJ, UK.

Emerging evidence suggests that G protein coupled receptor 55 (GPR55) may influence adrenoceptor function/activity in the cardiovascular system. Whether this reflects direct interaction (dimerization) between receptors or signalling crosstalk has not been investigated. This study explored the interaction between GPR55 and the alpha 1A-adrenoceptor (α-AR) in the cardiovascular system and the potential to influence function/signalling activities. GPR55 and α-AR mediated changes in both cardiac and vascular function was assessed in male wild-type (WT) and GPR55 homozygous knockout (GPR55) mice by pressure volume loop analysis and isolated vessel myography, respectively. Dimerization of GPR55 with the α-AR was examined in transfected Chinese hamster ovary-K1 (CHO-K1) cells via Bioluminescence Resonance Energy Transfer (BRET). GPR55 and α-AR mediated signalling (extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation) was investigated in neonatal rat ventricular cardiomyocytes using AlphaScreen proximity assays. GPR55 mice exhibited both enhanced pressor and inotropic responses to A61603 (α-AR agonist), while in isolated vessels, A61603 induced vasoconstriction was attenuated by a GPR55-dependent mechanism. Conversely, GPR55-mediated vasorelaxation was not altered by pharmacological blockade of α-ARs with tamsulosin. While cellular studies demonstrated that GPR55 and α-AR failed to dimerize, pharmacological blockade of GPR55 altered α-AR mediated signalling and reduced ERK1/2 phosphorylation. Taken together, this study provides evidence that GPR55 and α-AR do not dimerize to form heteromers, but do interact at the signalling level to modulate the function of α-AR in the cardiovascular system.
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http://dx.doi.org/10.1016/j.bcp.2021.114560DOI Listing
May 2021

Lung Transplantation for Pleuroparenchymal Fibroelastosis.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Pleuroparenchymal fibroelastosis (PPFE), a new disease entity associated with interstitial pneumonia, is characterized by fibrosis and elastosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobe. As the awareness of this disease entity has increased, many studies have revealed the prevalence and incidence, clinical and pathological characteristics, and disease course of PPFE. Patients with PPFE reportedly have several unique clinical characteristics-including an extremely low body mass index with a slender body and chest wall deformity, known as "flat chest". As this disease progresses, shrinking of the lungs often causes life-threatening complications, such as pneumothorax, and associated air leak syndrome. Lung transplantation is considered the only effective treatment for patients with advanced PPFE; however, little is known about the influences of the characteristics of PPFE on the outcome of lung transplantation. This review focuses on the unique clinicopathologic characteristics of PPFE and associated outcomes of lung transplantation for these patients.
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http://dx.doi.org/10.3390/jcm10050957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957581PMC
March 2021

Lung autotransplantation for bronchial necrosis after radiotherapy: a case report.

Surg Case Rep 2021 Apr 1;7(1):79. Epub 2021 Apr 1.

Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Background: Bronchial necrosis is a rare but fatal complication after radiation therapy. Because of the anatomical complexity and rarity of this condition, determining the most appropriate management for individual patients is extremely challenging. Lung autotransplantation is a surgical technique that has been applied to hilar neoplastic lesions to preserve pulmonary function and avoid pneumonectomy. We herein report a case of bronchial necrosis secondary to radiotherapy that was treated with lung autotransplantation.

Case Presentation: A 46-year-old man developed broad necrosis and infection of the right bronchus secondary to previous stereotactic body-radiation therapy. This treatment was supplied close to a right hilar metastatic pulmonary tumor derived from a mediastinal malignant germ cell tumor that had been surgically resected with the left phrenic nerve. The bronchial necrosis accompanied by infection with Aspergillus fumigatus was progressive despite antibiotics and repetitive bronchoscopic debridement. Because of the patient's critical condition and limited pulmonary function, right lung autotransplantation with preservation of the right basal segment was selected. An omental flap was placed around the bronchial anastomosis to prevent later complications. The postoperative course involved multiple complications including contralateral pneumonia and delayed wound healing at the bronchial anastomosis with resultant stenosis, the latter of which was overcome by placement of a silicone stent. The patient was discharged 5 months postoperatively. Three months after discharge, however, the patient developed hemoptysis and died of bronchopulmonary arterial fistula formation.

Conclusions: We experienced an extremely challenging case of bronchial necrosis secondary to radiotherapy. The condition was managed with lung autotransplantation and omental wrapping; however, the treatment success was temporary and the patient eventually died of bronchopulmonary arterial fistula formation. This technique seems to be a feasible option for locally advanced refractory bronchial necrosis, although later complications can still be fatal.
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http://dx.doi.org/10.1186/s40792-021-01164-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017021PMC
April 2021

Layilin promotes mitochondrial fission by cyclin-dependent kinase 1 and dynamin-related protein 1 activation in HEK293T cells.

Biochem Biophys Res Commun 2021 Apr 3;549:143-149. Epub 2021 Mar 3.

Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa, 216-8511, Japan. Electronic address:

Object: Functions of layilin, a type 1 transmembrane protein with a C-type lectin motif, remain to be clarified. We here investigated precise intracellular localization of layilin and the location-related functions.

Methods: We used HEK293T cells to assess the co-localization of layilin with different individual organelle markers by double immunostaining. We then investigated mitochondrial morphology in layilin-knockdown (KD) conditions, also with immunostaining. Next, we measured amounts of proteins involved in regulation of mitochondrial dynamics, DRP1, pS616-DRP1, mitofusin1, mitofusin2, CDK1, pY15-CDK1, and cyclin B1, in layilin-KD cells versus control cells by Western blot. Furthermore, by using layilin-knockout (KO) cells, amounts of CDK1 and pY15-CDK1 as well as mitochondrial morphology were investigated.

Result: We found that layilin localized to mitochondria rather than the other organelles. Small round-shape mitochondria were observed in control cells, whereas elongated and highly connected mitochondria were observed in layilin-KD cells. Amounts of active DRP1 (pS616-DRP1) and total DRP1 were significantly smaller in layilin-KD cells than in controls. Amounts of inactive CDK1 (pY15-CDK1) were significantly larger in layilin-KD cells than in controls. No other tested molecules were significantly altered in layilin-KD cells. Amounts of inactive CDK1 were significantly larger in layilin-KO cells than in wild type (WT) cells. Small round-shape mitochondria were observed in WT cells, whereas elongated and highly connected mitochondria were observed in layilin-KO cells.

Conclusion: We here demonstrated that layilin played a role in the maintenance of fragmented mitochondria in mitochondrial dynamics and that this function needed CDK1 and DRP1 activation. Our data unveiled a novel function for layilin, regulation of mitochondrial dynamics.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.091DOI Listing
April 2021

Familial interstitial pneumonia revealed after living-donor lobar lung transplantation.

Ann Thorac Surg 2021 Mar 1. Epub 2021 Mar 1.

Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.

Living-donor lobar lung transplantation (LDLLT) is often indicated for acute exacerbation of idiopathic interstitial pneumonia (IIP) because of the long waiting time for cadaveric lung transplantation in Japan. Donors without major underlying diseases are selected after medical screening. A 44-year-old man donated his right lower lobe to his sibling with IIP. Although he was free of any major medical problems before LDLLT, fibrotic changes appeared in both the donated lung and the donor's remaining lungs in a case of familial interstitial pneumonia. In LDLLT for IIP, donor candidates should be informed of the potential issue of a familial disease.
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http://dx.doi.org/10.1016/j.athoracsur.2021.02.021DOI Listing
March 2021

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

Surg Today 2021 Feb 12. Epub 2021 Feb 12.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF).

Methods: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018.

Results: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m vs. 1 year post-transplant, 15.6 ± 2.5 kg/m; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01).

Conclusions: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.
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http://dx.doi.org/10.1007/s00595-021-02232-6DOI Listing
February 2021

Resection of clustered arteriovenous malformations to avoid lung transplantation.

Ann Thorac Surg 2021 Feb 1. Epub 2021 Feb 1.

Department of Thoracic Surgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan.

A 54-year-old man with hereditary hemorrhagic telangiectasia and severe hypoxemia was referred for lung transplantation. Embolization had not been performed because of numerous bilateral small pulmonary arteriovenous malformations. Although he appeared to be qualified for lung transplantation, we instead performed bilateral thoracoscopic multiple wide wedge resections because of his age, lifestyle as a farmer, and relatively clustered distribution of arteriovenous malformations. Intermittent bilateral ventilation was needed because of poor oxygenation in the early stages of surgery, but his oxygenation improved as the resection progressed. His postoperative oxygenation improved significantly, and lung transplantation was avoided.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.035DOI Listing
February 2021

The modified water swallowing test score is the best predictor of postoperative pneumonia following extubation in cardiovascular surgery: A retrospective cohort study.

Medicine (Baltimore) 2021 Jan;100(4):e24478

Department of Rehabilitation Medicine, Shinshu University Hospital.

Abstract: No guidelines have been established for the evaluation of swallowing function following extubation. The factors of bedside swallowing evaluations (BSEs) that are associated with the development of pneumonia have not been fully elucidated. This study aimed to retrospectively investigate the most appropriate measurements of BSEs for predicting pneumonia.The study subjects were 97 adults who underwent BSEs following cardiovascular surgery. Patients were divided into the pneumonia onset group (n = 21) and the non-onset group (n = 76). Patient characteristics, intraoperative characteristics, complications, BSE results, and postoperative progress were compared between the groups. BSEs were composed of consciousness level, modified water swallowing test (MWST) score, repetitive saliva swallowing test score, speech intelligibility score, and risk of dysphagia in the cardiac surgery score. Univariate and multivariate analyses with the BSE as the independent variable and pneumonia onset as the dependent variable were also performed to identify factors that predict pneumonia. For factors that became significant in univariate analysis, the incidence of pneumonia was shown using the Kaplan-Meier curve.No significant differences were found in patient characteristics, intraoperative characteristics, and complications between the 2 groups. The postoperative progress was significantly different between the 2 groups, the pneumonia-onset group had a significantly longer time until the start of oral intake and a significantly lower median value of Food Intake Level Scale at the time of discharge. According to univariate and multivariate analyses, MWST score was a significant factor for predicting the onset of pneumonia even after adjusting for patient characteristics and surgical factors, and the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less.The MWST score after extubation in cardiovascular surgery was the strongest predictor of postoperative pneumonia in BSEs. Furthermore, the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less. Predicting cases with a high risk of developing pneumonia allows nurses and attending physicians to monitor the progress carefully and take aggressive preventive measures.
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http://dx.doi.org/10.1097/MD.0000000000024478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850752PMC
January 2021

Primary pulmonary lymphoepithelioma-like carcinoma with positive expression of Epstein-Barr virus and PD-L1: A case report.

Int J Surg Case Rep 2021 Feb 20;79:431-435. Epub 2021 Jan 20.

Department of Thoracic Surgery, Sapporo Minami-sanjo Hospital, Sapporo, Hokkaido, Japan.

Introduction And Importance: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC) that is classified as a subtype of unclassified carcinoma by the WHO. LELC is usually associated with Epstein-Barr virus (EBV) infection. LELC has often been observed in Southeast Asia; however, it is extremely rare in Japan.

Case Presentation: A 60-year-old Japanese woman presented with an abnormal shadow in the left lung on chest radiography. Chest computed tomography showed a nodule located between the lingular and basal anteromedial segments. A blood test suggested an existing EBV infection, and LELC was suspected preoperatively in the transbronchial lung biopsy. She underwent a lingular and basal bi-segmentectomy. The EBV-encoded small ribonucleic acid in-situ hybridization (EBER-ISH) was positive, and she was diagnosed with LELC. Moreover, programmed death-ligand 1 (PD-L1) expression was moderately positive. No recurrence was observed for 30 months.

Clinical Discussion: Although LELC has been reported as a low-grade malignancy with a good prognosis, the frequency of PD-L1 expression in LELC seems to be higher than that in other NSCLCs. Moreover, it has been reported that LELC patients with high PD-L1 expression are likely to have early recurrence/metastasis and poor prognosis.

Conclusion: An investigation of PD-L1 expression for LELC would be useful considering the benefit of PD-1/PD-L1 blockade in patients with pulmonary LELC with high PD-L1 expression. The present case is the first report of LELC with positive expression of EBER-ISH and PD-L1 in Japan.
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http://dx.doi.org/10.1016/j.ijscr.2021.01.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851415PMC
February 2021

Multiple coordinated cellular dynamics mediate CA1 map plasticity.

Hippocampus 2021 Mar 16;31(3):235-243. Epub 2021 Jan 16.

RIKEN Brain Science Institute, Wako, Saitama, Japan.

In the hippocampus, spatial and nonspatial information are jointly represented as a neural map in which locations associated with salient features are over-represented by increased densities of relevant place cells. Although we recently demonstrated that experience-dependent establishment of these disproportionate maps is governed by selective stabilization of salient place cells following their conversion from non-place cells, the underlying mechanism for pre-established map reorganization remained to be understood. To this end, we investigated the changes in CA1 functional cellular maps imaged using two-photon calcium imaging in mice performing a reward-rearrangement task in virtual reality. Mice were pre-trained on a virtual linear track with a visual landmark and a reward in two distinct locations. Then, they were re-trained on the same track with the exception that the location of reward was shifted to match the landmark location. We found that, in contrast to de novo map formation, robust map reorganization occurred through parallel coordination of new place field formation, lateral shifting of existing place fields, and selective stabilization of place fields encoding salient locations. Our findings demonstrate that intricate interplay between multiple forms of cellular dynamics enables rapid updating of information stored in hippocampal maps.
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http://dx.doi.org/10.1002/hipo.23300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986426PMC
March 2021

Management of partial anomalous pulmonary venous return in lung transplantation.

Ann Thorac Surg 2021 Jan 10. Epub 2021 Jan 10.

Department of Thoracic Surgery, The University of Tokyo Hospital: 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

We present the case of a patient who underwent bilateral lung transplantation for idiopathic pulmonary arterial hypertension with coexisting partial anomalous pulmonary venous return and tracheal bronchus. The hypoplastic and low-positioned left atrial orifice caused by abnormal reflux of the right upper pulmonary vein and high-positioned right upper lobe bronchus made right anastomosis challenging. To prevent excessive tension on left atrial anastomosis, the donor's right main bronchus was anastomosed to the recipient's bronchus intermedius, which resulted in successful anastomosis and an uneventful postoperative course.
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http://dx.doi.org/10.1016/j.athoracsur.2020.10.072DOI Listing
January 2021

Identification of novel substrates of a disintegrin and metalloprotease 17 by specific labeling of surface proteins.

Heliyon 2020 Dec 22;6(12):e05804. Epub 2020 Dec 22.

Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine.

A disintegrin and metalloprotease 17 (ADAM17) catalyzes the cleavage and release of the ectodomains of its substrates at the cell surface in a process termed ectodomain shedding. However, not all ADAM17 substrates have been identified. Here, we used cell surface protein-specific labeling and proteomic approaches to detect and identify ADAM17 substrates. HeLa cell surface proteins were labeled with a fluorescent dye and cultured with or without TAPI-2, an ADAM17 inhibitor. Labeled proteins released into the culture medium were detected by 2-dimensional gel electrophoresis (2DE). Protein spots showing decreased intensity in response to TAPI-2 were selected as substrates of ADAM17 or their binding proteins, and identified by mass spectrometry. knockdown was preformed to examine the behavior of identified proteins. Of 347 proteins detected by 2DE, 49 showed lower intensity in TAPI-2 (+) than in TAPI-2 (-) samples (p < 0.05), and were considered as candidate substrates of ADAM17. Mass spectrometric analysis of 14 protein spots showing >50% decreased intensity identified clusterin as a novel ADAM17 substrate, in addition to known substrates such as desmoglein-2. Western blot analysis showed that knockdown decreased the levels of clusterin fragments cleaved and released from the cell surface. The results identified clusterin as a novel ADAM17 substrate. The method used to identify clusterin could be used to identify the substrates of other sheddases involved in ectodomain shedding.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770542PMC
December 2020

Simultaneous single lobar lung transplantation and contralateral lung volume reduction.

Eur J Cardiothorac Surg 2020 Dec 24. Epub 2020 Dec 24.

Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.

Lung transplantation (LTx) and lung volume reduction surgery are established therapies for end-stage chronic obstructive pulmonary disease. Although native lung hyperinflation is a well-known complication of unilateral LTx for chronic obstructive pulmonary disease, the unilateral procedure continues to be performed because of severe shortages of cadaveric donors. As native lung hyperinflation can adversely affect the graft, all possible protection should be provided for patients with one-lobe transplantation. We report an emphysematous juvenile patient who successfully underwent simultaneous living-donor, single-lobe LTx and volume reduction in the contralateral lung.
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http://dx.doi.org/10.1093/ejcts/ezaa459DOI Listing
December 2020

Respiratory strength and pectoralis muscle mass as measures of sarcopenia: Relation to outcomes in resected non-small cell lung cancer.

J Thorac Cardiovasc Surg 2020 Nov 19. Epub 2020 Nov 19.

Department of Thoracic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Objectives: Physical biomarkers to stratify patients with lung cancer into subtypes predictive of outcome beyond tumor-related characteristics are underexplored. This study was designed to investigate the clinical utility of preoperative sarcopenia based on respiratory strength and pectoralis muscle mass to predict the risk of death.

Methods: This retrospective study included 346 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. Respiratory strength and muscle mass were assessed by peak expiratory flow rate and pectoralis muscle index (pectoralis muscle area/body mass index) using preoperative spirometry and chest axial images, respectively. Sarcopenia cutoff points were defined by gender-specific medians of peak expiratory flow rates and pectoralis muscle indices. Survival was compared between patients with sarcopenia and patients without.

Results: Sarcopenia was present in 98 patients (28.3%) and was significantly associated with advancing age (P < .001). Patients with sarcopenia exhibited worse 5-year overall survival compared with patients without sarcopenia (69.9% vs 87.2%, P < .001). Multivariate analysis revealed that sarcopenia was an independent adverse prognostic factor (hazard ratio, 1.88; 95% confidence interval, 1.09-3.24; P = .023) after adjustment for gender, age, smoking status, coronary heart disease, diffusing capacity for carbon monoxide, neutrophil-to-lymphocyte ratio, albumin, histologic type, and pathologic stage.

Conclusions: Preoperative sarcopenia as identified by the criteria of low respiratory strength and reduced pectoralis muscle mass is significantly associated with poor overall survival. This may help to develop more individualized management strategies and optimize longitudinal care for patients.
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http://dx.doi.org/10.1016/j.jtcvs.2020.10.133DOI Listing
November 2020

Cerebral Hemodynamics During a Cognitive-Motor Task Using the Limbs.

Front Hum Neurosci 2020 10;14:568030. Epub 2020 Nov 10.

Division of Occupational Therapy School of Health Science, Faculty of Medicine, Shinshu University, Matsumoto, Japan.

: Antagonistic tasks are cognitive-motor task trainings. Intervention programs involving antagonistic exercise tasks are being employed to help prevent falls and reduce the need for nursing care in older populations. Meanwhile, the effects of such tasks on blood flow in the brain remain obscure. This study aimed to clarify the effects of antagonistic tasks on prefrontal cortical cerebral hemodynamics. : We assessed 13 healthy adults (two men, 11 women; mean age, 21.4 ± 1.0 years). Participants imitated each of the antagonistic tasks presented on a PC monitor placed at a 120-mm viewing distance. All participants performed six tasks, consisting of upper-limb tasks (non-antagonism, simple antagonism, and complex antagonism) and upper- and lower-limb tasks (tasks combining lower-limb opening and closing movements with each upper-limb task). We used near-infrared spectroscopy (NIRS) to measure cerebral blood flow dynamics, with oxygenated hemoglobin (Oxy-Hb) concentration changes as the main outcome. A 10-channel probe was placed on the participants' forehead, focusing on the prefrontal cortex. We first obtained a baseline NIRS measurement for 10 s; the participants then imitated the task presented on the PC monitor for 90 s. We measured the number of errors and the subjective difficulty of each task. : The increase in prefrontal cortex Oxy-Hb concentration was significantly higher in the complex antagonist conditions than in the non-antagonistic and simple antagonistic conditions. There were no significant prefrontal cortex Oxy-Hb differences between the upper limb and upper- and lower-limb conditions (increasing number of motor limbs). : The study findings support that an increase in finger-shaped complexity has a greater effect on cerebral blood flow dynamics in the prefrontal cortex than does an increase in the number of motor limbs involved in the task.
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http://dx.doi.org/10.3389/fnhum.2020.568030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683383PMC
November 2020

Exacerbation of Secondary Pulmonary Hypertension by Flat Chest after Lung Transplantation.

Ann Thorac Cardiovasc Surg 2020 Nov 3. Epub 2020 Nov 3.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

A 40-year-old woman with idiopathic pleuroparenchymal fibroelastosis (IPPFE) and flat chest underwent left single lung transplantation (SLT). Although she had developed over-systemic pulmonary arterial pressure (PAP) at transplantation, it was alleviated. However, her PAP gradually increased again. Her transplanted lung was well-inflated, but progression of fibrosis in her right native lung appeared to have caused a mediastinal shift, and her flat chest caused obstruction of the outflow tract of the pulmonary vein. She died of heart failure and associated infection 1.5 years after transplantation. An autopsy confirmed irreversible pulmonary arterial and venous changes in the transplanted lung, suggestive of chronic pressure overload. The flat chest associated with IPPFE can affect pulmonary circulation after SLT.
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http://dx.doi.org/10.5761/atcs.cr.20-00230DOI Listing
November 2020

A new method for accurately localizing and resecting pulmonary nodules.

J Thorac Dis 2020 Sep;12(9):4973-4984

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

With the use of low-dose CT for early screening of lung cancer, more and more early lung cancers are found. At the same time, patients with small lung nodules have also increased, it is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. Many studies have reported preoperative and intraoperative methods for localizing lung nodules before minimally invasive resection. Methods for preoperative localization include CT-guided hook-wire positioning, coil positioning, or dye injection and radionuclide location Methods for intraoperative localization include intraoperative ultrasound localization and tactile pressure-sensing localization. After the localization of pulmonary nodules under the guidance of CT patients need to restrict their activities; otherwise, it is easy for the nodules to move, causing the operation to fail, and may also cause complications such as pneumothorax, puncture site pain, and pulmonary parenchymal bleeding. In the past, we injected melamine dye under the guidance of electromagnetic navigation bronchoscope to locate lung nodules. The purpose of this case is introducing a new method for accurately localizing and resecting pulmonary nodules by injecting indocyanine green (ICG) under the guidance of electromagnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope.
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http://dx.doi.org/10.21037/jtd-20-2089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578447PMC
September 2020

A case report of idiopathic pleuroparenchymal fibroelastosis with severe respiratory failure in pregnancy.

BMC Pulm Med 2020 Oct 14;20(1):264. Epub 2020 Oct 14.

Department of Obstetrics and Gynecology, Showa University Northern Yokohama Hospital, Chigasaki-chuo 35-1, Tsuzuki- ku, Yokohama-shi, Kanagawa, 224-8503, Japan.

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare lung disease that manifests as parenchymal fibrosis of the upper lung lobe and pleura. There have been no reports of IPPFE complicating pregnancy. Here, we report a case of IPPFE that deteriorated rapidly during pregnancy.

Case Presentation: A 29-year-old woman presented with dyspnea and dry cough at 19 weeks of gestation. IPPFE with acute exacerbation was suspected on chest computed tomography (CT). Despite steroid treatment, her condition progressed. A cesarean section was performed at 28 weeks of gestation. On postoperative day 26, she underwent living-donor lung transplantation. She was discharged a year after transplantation.

Conclusion: Our experience suggested that when pregnancy is complicated by PPFE, the disease may deteriorate rapidly. In this case, even though IPPFE with acute exacerbation was diagnosed during pregnancy, live birth was achieved, and the mother survived after lung transplantation. Lung transplantation should be considered in these patients because, once advanced, pulmonary lesions may be irreversible.
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http://dx.doi.org/10.1186/s12890-020-01308-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556914PMC
October 2020

Encoding of social exploration by neural ensembles in the insular cortex.

PLoS Biol 2020 09 21;18(9):e3000584. Epub 2020 Sep 21.

RIKEN Brain Science Institute, Wako, Saitama, Japan.

The insular cortex (IC) participates in diverse complex brain functions, including social function, yet their cellular bases remain to be fully understood. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely moving and restrained social targets, we identified 2 subsets of AI neurons-a larger fraction of "Social-ON" cells and a smaller fraction of "Social-OFF" cells-that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during exploration under a particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.
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http://dx.doi.org/10.1371/journal.pbio.3000584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529241PMC
September 2020

Tumor Maximum Area May Determine the Survival Outcomes of Patients with Thymic Epithelial Tumors.

Ann Surg Oncol 2021 Apr 19;28(4):2078-2085. Epub 2020 Sep 19.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Background: The tumor maximum area (TMA) of thymic epithelial tumors (TETs) is not mentioned in current staging systems. This study aimed to assess whether TMA is of prognostic significance in TETs.

Methods: Patients who underwent extended thymectomy for TETs from 2001 to 2019 at our institute were retrospectively reviewed. TMA was examined by computed tomography imaging prior to surgery. Time-dependent receiver operating characteristic (ROC) curves were used to divide the cohort into two groups. The relationships between the TMA and clinicopathological characteristics or survival outcomes were assessed. Cox proportional hazards models were used to identify independent prognostic factors.

Results: A total of 122 TET patients were included for evaluation, with a median age of 61 years (range 27-83). The time-dependent ROC curve indicated that the difference in 10-year overall survival (OS) was most significant for a TMA of 1392 mm (area under the curve 0.793); therefore, the two groups of larger (n = 40) and smaller (n = 82) TMAs were divided. The differences in adjuvant therapy, TNM stage, and disease progression between the two groups were significant (p < 0.05). Kaplan-Meier curves indicated that TET patients with a larger TMA had worse survival outcomes, including OS, progression-free survival (PFS) and disease-free survival (DFS) [p < 0.05]. TMA was demonstrated to be an independent prognostic factor of all of the above survival outcomes in multivariate analysis (p < 0.05).

Conclusions: A larger TMA is associated with a more advanced TNM stage and disease progression in TET patients and may indicate worse survival outcomes, even if more patients receive adjuvant therapy.
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http://dx.doi.org/10.1245/s10434-020-09127-9DOI Listing
April 2021

Native Lung Pulmonary Artery Banding After Single-Lung Transplant for Obliterative Bronchiolitis.

Ann Thorac Surg 2021 04 17;111(4):e253-e255. Epub 2020 Sep 17.

Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.

Single-lung transplantation (LTx) is an option for lung injury after bone marrow transplantation. We report a patient who underwent right single LTx for obliterative bronchiolitis after bone marrow transplantation and suffered post-LTx hypoxemia because of a marked ventilation-perfusion mismatch in his native lung. Pulmonary artery banding at 78 days after LTx decreased pulmonary arterial flow to the native lung and successfully resolved the hypoxemia. When we encounter hypoxemia after single LTx, ventilation-perfusion mismatch in the native lung should be considered as a possible diagnosis and surgical pulmonary artery banding is a feasible option.
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http://dx.doi.org/10.1016/j.athoracsur.2020.06.121DOI Listing
April 2021

Adoptive transfer of zoledronate-expanded autologous Vγ9Vδ2 T-cells in patients with treatment-refractory non-small-cell lung cancer: a multicenter, open-label, single-arm, phase 2 study.

J Immunother Cancer 2020 09;8(2)

Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

Background: Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC.

Methods: NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×10) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months.

Results: Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0-479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%-20.4%) and 68.0% (46.5%-85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor.

Conclusions: Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint.

Trial Registration Number: UMIN000006128.
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http://dx.doi.org/10.1136/jitc-2020-001185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511646PMC
September 2020

Chronic lung allograft dysfunction post-lung transplantation: The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome.

World J Transplant 2020 May;10(5):104-116

Department of Thoracic Surgery, The University of Tokyo Hospital, Tokyo 113-8655, Japan.

Chronic lung allograft dysfunction (CLAD) following lung transplantation limits long-term survival considerably. The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment. The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes: Bronchiolitis obliterans syndrome and restrictive allograft syndrome. Along with this clear classification, further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired. In this review, we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome, which have been elucidated from clinicopathological observations and animal experiments worldwide.
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http://dx.doi.org/10.5500/wjt.v10.i5.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428788PMC
May 2020

Imaging the Neural Circuit Basis of Social Behavior: Insights from Mouse and Human Studies.

Neurol Med Chir (Tokyo) 2020 Sep 31;60(9):429-438. Epub 2020 Aug 31.

RIKEN Center for Brain Science.

Social behavior includes a variety of behaviors that are expressed between two or more individuals. In humans, impairment of social function (i.e., social behavior and social cognition) is seen in neurodevelopmental and neurological disorders including autism spectrum disorders (ASDs) and stroke, respectively. In basic neuroscience research, fluorescence monitoring of neural activity, such as immediate early gene (IEG)-mediated whole-brain mapping, fiber photometry, and calcium imaging using a miniaturized head-mounted microscope or a two-photon microscope, and non-fluorescence imaging such as functional magnetic resonance imaging (fMRI) are increasingly used to measure the activity of many neurons and multiple brain areas in animals during social behavior. In this review, we overview recent rodent studies that have investigated the dynamics of brain activity during social behavior at the whole-brain and local circuit levels and studies that explored the neural basis of social function in healthy, in brain-injured, and in autistic human subjects. A synthesis of such findings will advance our understanding of brain mechanisms underlying social behavior and facilitate the development of pharmaceutical and functional neurosurgical interventions for brain disorders affecting social function.
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http://dx.doi.org/10.2176/nmc.ra.2020-0088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490602PMC
September 2020

The metabolic effects of mirabegron are mediated primarily by β -adrenoceptors.

Pharmacol Res Perspect 2020 10;8(5):e00643

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia.

The β -adrenoceptor agonist mirabegron is approved for use for overactive bladder and has been purported to be useful in the treatment of obesity-related metabolic diseases in humans, including those involving disturbances of glucose homeostasis. We investigated the effect of mirabegron on glucose homeostasis with in vitro and in vivo models, focusing on its selectivity at β-adrenoceptors, ability to cause browning of white adipocytes, and the role of UCP1 in glucose homeostasis. In mouse brown, white, and brite adipocytes, mirabegron-mediated effects were examined on cyclic AMP, UCP1 mRNA, [ H]-2-deoxyglucose uptake, cellular glycolysis, and O consumption. Mirabegron increased cyclic AMP levels, UCP1 mRNA content, glucose uptake, and cellular glycolysis in brown adipocytes, and these effects were either absent or reduced in white adipocytes. In brite adipocytes, mirabegron increased cyclic AMP levels and UCP1 mRNA content resulting in increased UCP1-mediated oxygen consumption, glucose uptake, and cellular glycolysis. The metabolic effects of mirabegron in both brown and brite adipocytes were primarily due to actions at β -adrenoceptors as they were largely absent in adipocytes derived from β -adrenoceptor knockout mice. In vivo, mirabegron increased whole body oxygen consumption, glucose uptake into brown and inguinal white adipose tissue, and improved glucose tolerance, all effects that required the presence of the β -adrenoceptor. Furthermore, in UCP1 knockout mice, the effects of mirabegron on glucose tolerance were attenuated. Thus, mirabegron had effects on cellular metabolism in adipocytes that improved glucose handling in vivo, and were primarily due to actions at the β -adrenoceptor.
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http://dx.doi.org/10.1002/prp2.643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437350PMC
October 2020

International Society for Heart and Lung Transplantation consensus statement for the standardization of bronchoalveolar lavage in lung transplantation.

J Heart Lung Transplant 2020 Jul 15. Epub 2020 Jul 15.

Lung Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.
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http://dx.doi.org/10.1016/j.healun.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361106PMC
July 2020

Prognostic significance of low pectoralis muscle mass on preoperative chest computed tomography in localized non-small cell lung cancer after curative-intent surgery.

Lung Cancer 2020 09 7;147:71-76. Epub 2020 Jul 7.

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Objectives: The impact of sarcopenia on the outcome in patients following resection of non-small cell lung cancer is yet to be fully determined. This study aimed to evaluate the clinical utility of a computed tomography-based pectoralis muscle assessment, which reflects sarcopenia, to predict the risk of postoperative outcomes.

Materials And Methods: This retrospective study included 347 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. The pectoralis muscle index (pectoralis muscle area/body mass index) was assessed at the level of the fourth thoracic vertebra on chest axial images. The primary outcomes were compared between the lowest gender-specific quintile (sarcopenia) and the other quintiles according to the index. The prognostic significance of low pectoralis muscle index was calculated by the Cox proportional hazards regression model. A propensity score matching analysis was performed to adjust the differences in clinical characteristics.

Results: Sixty-nine patients were identified with sarcopenia according to the lowest gender-specific quintile of pectoralis muscle index. Patients with sarcopenia exhibited worse 5-year overall survival rate compared with patients without sarcopenia (64.2 % vs. 86.7 %, P < 0.001). Even in stage I non-small cell lung cancer, the rate of 5-year overall survival in the sarcopenia group was lower than that in the non-sarcopenia group (74.2 % vs. 92.4 %, P = 0.001). Multivariate analysis revealed that low pectoralis muscle index was independently associated with adverse overall survival (hazard ratio: 2.09, 95 % confidence interval: 1.20-3.62, P = 0.009). After propensity score matching, the prognostic impact of sarcopenia based on low pectoralis muscle index was also robust for overall survival (hazard ratio: 3.23, 95 % confidence interval: 1.38-7.60, P = 0.007).

Conclusions: Low pectoralis muscle index was significantly associated with poor long-term outcomes in patients with localized non-small cell lung cancer after curative surgery. This may help assist preoperative risk stratification and longitudinal management after surgery.
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http://dx.doi.org/10.1016/j.lungcan.2020.07.008DOI Listing
September 2020

Preoperative lung surface localization for pulmonary wedge resection: a single-center experience.

J Thorac Dis 2020 May;12(5):2129-2136

Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Background: Preoperative lung surface localization is effective in sublobar resection for small lung nodules. However, the efficacy may vary depending on the underlying conditions of the lung and tumor, as well as the technique. This study aimed to evaluate the efficacy and limitations of preoperative lung surface localization for wedge resection by analyzing the outcomes of computed tomography (CT)-guided percutaneous marking and virtual-assisted lung mapping (VAL-MAP).

Methods: We investigated 215 patients who underwent curative wedge resection for malignant tumors using CT-guided localization or VAL-MAP from 1998 to 2018 in our institute. Each resected nodule was assessed for successful resection, which was defined as complete resection with adequate margins.

Results: One-hundred-and-nineteen patients with 153 nodules were included. The overall successful resection rate was 87.6%. The successful resection rate was significantly lower for nodules with intraoperative adhesion than those without intraoperative adhesion (75.0% 90.1%; P=0.034), and for tumors requiring deep resection margins (>31 mm) than those requiring shallow margins (≤31 mm) (76.7% 94.6%; P=0.002). Although the successful resection rate for nodules resected using CT-guided localization was significantly lower in cases with versus without intraoperative adhesion (54.5% 86.7%; P=0.048), the successful resection rate for nodules resected using VAL-MAP was not influenced by the presence or absence of adhesion (85.7% 93.4%; P=0.491).

Conclusions: A requirement for deeper resection and the presence of intraoperative adhesion were limitations of preoperative lung surface localization for curative pulmonary wedge resection.
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http://dx.doi.org/10.21037/jtd.2020.04.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330346PMC
May 2020