Publications by authors named "Kenji Suzuki"

895 Publications

Smiles as a Signal of Prosocial Behaviors Toward the Robot in the Therapeutic Setting for Children With Autism Spectrum Disorder.

Front Robot AI 2021 26;8:599755. Epub 2021 May 26.

Faculty of Engineering, Information and Systems, University of Tsukuba, Tsukuba, Japan.

We explored how robot-assisted therapy based on smile analysis may facilitate the prosocial behaviors of children with autism spectrum disorder. Prosocial behaviors, which are actions for the benefit of others, are required to belong to society and increase the quality of life. As smiling is a candidate for predicting prosocial behaviors in robot-assisted therapy, we measured smiles by annotating behaviors that were recorded with video cameras and by classifying facial muscle activities recorded with a wearable device. While interacting with a robot, the participants experienced two situations where participants' prosocial behaviors are expected, which were supporting the robot to walk and helping the robot from falling. We first explored the overall smiles at specific timings and prosocial behaviors. Then, we explored the smiles triggered by a robot and behavior changes before engaging in prosocial behaviors. The results show that the specific timing of smiles and prosocial behaviors increased in the second session of children with autism spectrum disorder. Additionally, a smile was followed by a series of behaviors before prosocial behavior. With a proposed Bayesian model, smiling, or heading predicted prosocial behaviors with higher accuracy compared to other variables. Particularly, voluntary prosocial behaviors were observed after smiling. The findings of this exploratory study imply that smiles might be a signal of prosocial behaviors. We also suggest a probabilistic model for predicting prosocial behaviors based on smile analysis, which could be applied to personalized robot-assisted therapy by controlling a robot's movements to arouse smiles and increase the probability that a child with autism spectrum disorder will engage in prosocial behaviors.
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http://dx.doi.org/10.3389/frobt.2021.599755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187796PMC
May 2021

Correlation between the number of viable tumor cells and immune cells in the tumor microenvironment in non-small cell lung cancer after induction therapy.

Pathol Int 2021 Jun 11. Epub 2021 Jun 11.

Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.

This study aims to determine the correlation between the percent viable tumor cells (%VTC) and the tumor microenvironment in resected non-small cell lung cancer after induction therapy. We enrolled 72 patients with non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT) or chemotherapy (CT) prior to surgery. The ratio of the area of viable tumor cells to the total tumor area was calculated to obtain the %VTC. We also examined the number of CD4 (+), CD8 (+), CD20 (+) and FOXP3 (+) tumor-infiltrating lymphocytes (TILs), podoplanin (PDPN) (+) cancer-associated fibroblasts (CAFs), and CD204 (+) tumor-associated macrophages (TAMs) by immunohistochemistry (IHC). In the CRT group (n = 37), the tumors had significantly lower %VTC than the CT group (n = 35) (P < 0.001). In both of the CT group and CRT group, the %VTC showed a significant positive correlation with the number of CD204 (+)-TAMs (P = 0.014 and 0.005, respectively). Only in the CRT group, a higher number of CD204 (+) TAMs was associated with a shorter overall survival (OS) (P = 0.007) and recurrence-free survival (RFS) (P = 0.015). In the CRT group, the number of CD204 (+) TAMs is associated with %VTC and prognosis, suggesting that these cells may have tumor-promoting effects on the residual lung cancer in specific microenvironments after CRT.
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http://dx.doi.org/10.1111/pin.13110DOI Listing
June 2021

Surgical retrieval of an entrapped stent and a stuck snare device during percutaneous coronary intervention.

J Cardiol Cases 2021 Jun 6;23(6):287-289. Epub 2021 Apr 6.

Department of Cardiovascular Surgery, Nippon Medical School Musashikosugi Hospital, Japan.

A 69-year-old male patient with a history of percutaneous coronary intervention (PCI) to the proximal left anterior descending coronary artery (LAD) underwent another PCI to the stenosis of the medium LAD as part of therapy for angina pectoris. Interruption of stent delivery because of past stent led to stent entrapment and a stuck guidewire. A snare catheter device was applied to retrieve the stent; however, the device lost mobility. Surgical removal and coronary artery bypass grafting (CABG) were required. We herein report some surgical techniques for resolving this complication of PCI. < Despite the recent advancements in devices and/or technical skills, the complications of PCI will never be eliminated. This case report provides a suggestive lesson with regard to open heart surgery for PCI complication; furthermore, only a few reports have described details concerning these PCI complications from the viewpoint of a surgeon. Physicians and surgeons should learn the emergent surgical techniques for resolving PCI complications.>.
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http://dx.doi.org/10.1016/j.jccase.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165662PMC
June 2021

Clinical Impact of Stent Graft Thrombosis in Femoropopliteal Arterial Lesions.

JACC Cardiovasc Interv 2021 May;14(10):1137-1147

Department of Radiology, Nara Medical University, Kashihara, Japan.

Objectives: This study sought to elucidate the clinical impact and prognosis of stent graft (SG) thrombosis.

Background: The VIABAHN SG offers a favorable outcome in long peripheral artery occlusive disease (PAOD) lesions in the femoropopliteal artery. One concern after SG deployment is the incidence of stent thrombosis and consequent acute limb ischemia (ALI).

Methods: In this retrospective multicenter study, we collected the clinical data of PAOD patients treated with VIABAHN SG who subsequently experienced SG thrombosis. The clinical symptoms of SG thrombosis, patency after reintervention, and predictors of loss of patency after reintervention were examined.

Results: VIABAHN SGs were used for 1,215 patients; SG thrombosis occurred in 159 (13%) patients at a median of 6.4 months (interquartile range: 2.8 to 13.5 months) after SG implantation; 21 (13%) patients presented with ALI. A total of 131 (82%) patients underwent reintervention for SG thrombosis, whereas 2 (1%) underwent primary major amputation and the remaining 26 (16%) were treated conservatively. The patency rate 1 year after reintervention, freedom from major adverse limb events, and limb salvage after reintervention were 54.9%, 73.6%, and 92.5%, respectively. Critical limb-threatening ischemia at SG implantation and ALI presentation at SG thrombosis were positively associated with an increased risk of rethrombosis, whereas distal stent diameter was negatively associated with the risk of rethrombosis.

Conclusions: SG thrombosis is associated with a considerable risk of ALI, but the risk of primary major amputation was not high. Clinical outcomes after reinterventions for thrombosed SGs were suboptimal.
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http://dx.doi.org/10.1016/j.jcin.2021.03.030DOI Listing
May 2021

Transcription start site-level expression of thyroid transcription factor 1 isoforms in lung adenocarcinoma and its clinicopathological significance.

J Pathol Clin Res 2021 Jul 20;7(4):361-374. Epub 2021 May 20.

Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

There are multiple transcription start sites (TSSs) in agreement with multiple transcript variants encoding different isoforms of NKX2-1/TTF-1 (thyroid transcription factor 1); however, the clinicopathological significance of each transcript isoform of NKX2-1/TTF-1 in lung adenocarcinoma (LAD) is unknown. Herein, TSS-level expression of NKX2-1/TTF-1 isoforms was evaluated in 71 LADs using bioinformatic analysis of cap analysis of gene expression (CAGE)-sequencing data, which provides genome-wide expression levels of the 5'-untranslated regions and the TSSs of different isoforms. Results of CAGE were further validated in 664 LADs using in situ hybridisation. Fourteen of 17 TSSs in NKX2-1/TTF-1 (80% of known TSSs in FANTOM5, an atlas of mammalian promoters) were identified in LADs, including TSSs 1-13 and 15; four isoforms of NKX2-1/TTF-1 transcripts (NKX2-1_001, NKX2-1_002, NKX2-1_004, and NKX2-1_005) were expressed in LADs, although NKX2-1_005 did not contain a homeodomain. Among those, six TSSs regulated NKX2-1_004 and NKX2-1_005, both of which contain exon 1. LADs with low expression of isoforms from TSS region 11 regulating exon 1 were significantly associated with poor prognosis in the CAGE data set. In the validation set, 62 tumours (9.3%) showed no expression of NKX2-1/TTF-1 exon 1; such tumours were significantly associated with older age, EGFR wild-type tumours, and poor prognosis. In contrast, 94 tumours, including 22 of 30 pulmonary invasive mucinous adenocarcinomas (IMAs) exhibited exon 1 expression without immunohistochemical TTF-1 protein expression. Furthermore, IMAs commonly exhibited higher exon 1 expression relative to that of exon 4/5, which contained a homeodomain in comparison with EGFR-mutated LADs. These transcriptome and clinicopathological results reveal that LAD use at least 80% of NKX2-1 TSSs and expression of the NKX2-1/TTF-1 transcript isoform without exon 1 (NKX2-1_004 and NKX2-1_005) defines a distinct subset of LAD characterised by aggressive behaviour in elder patients. Moreover, usage of alternative TSSs regions regulating NKX2-1_005 may occur in subsets of LADs.
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http://dx.doi.org/10.1002/cjp2.213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185369PMC
July 2021

A risk model for prolonged air leak after lobectomy using the National Clinical Database in Japan.

Surg Today 2021 May 17. Epub 2021 May 17.

Japanese Association for Chest Surgery, Kyoto, Japan.

Purpose: The objective of our study was to develop a clinical prediction model for prolonged air leak (PAL) after lobectomy for lung cancer using preoperative variables in a large patient dataset from the National Clinical Database (NCD) in Japan.

Methods: The preoperative characteristics of 57,532 and 30,967 patients who had undergone standard lobectomy for lung cancer were derived from the 2014 to 2015 and 2016 NCD datasets, respectively. PAL was defined as air leak persisting ≥ 7 days postoperatively or requiring postoperative interventional treatment, such as pleurodesis or reoperation. Risk models were developed from the 2014 to 2015 dataset and validated using the 2016 dataset. When performing model derivation, the least absolute shrinkage and selection operator (LASSO) method were applied for parameter selection.

Results: The rate of PAL was 4.5% in 2014-2015 and 5.3% in 2016. The age, sex, body mass index, comorbid interstitial pneumonia, smoking habits, forced expiratory volume in 1 s, tumor histology, multiple lung cancer, and tumor location were selected as important variables for PAL. Our risk model for predicting PAL was fair with a concordance index of 0.6895.

Conclusion: The LASSO-based risk model for PAL after lobectomy provided important preoperative variables for PAL and risk weighting for each variable.
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http://dx.doi.org/10.1007/s00595-021-02300-xDOI Listing
May 2021

A nationwide web-based survey of factors associated with depressive symptoms among Japanese workers.

Int J Soc Psychiatry 2021 May 13:207640211017586. Epub 2021 May 13.

Center for Clinical Epidemiology and Health Technology Assessment, St. Luke's International University, Tokyo, Japan.

Background: Precarious employment has affected mental health, and limited data are available on the association of low stress tolerance with depressive symptoms among Japanese workers.

Aims: This study aimed to examine the relationship between stress tolerance and depressive symptoms among Japanese workers, including company employees, civil servants and self-employed persons in various industries.

Methods: We conducted a nationwide cross-sectional study. From March 26 to April 6, 2020, we performed a web-based survey of Japanese workers. The questionnaire included questions on socioeconomic factors, the SOC scale that assesses stress tolerance, the CES-D, and the EQ-5D-5L. Multivariate regression analyses were performed to determine the factors associated with depressive symptoms.

Results: We included 3,001 participants in the analysis. A high SOC score, adequate sleeping time and frequency of exercise were associated with higher depressive symptoms. Employment status and long working hours were not associated with depressive symptoms. Younger workers had lower SOC scores than older workers. An inverse correlation between the SOC score and CES-D score was found among Japanese workers.

Conclusions: Improving stress tolerance among younger workers is needed to prevent worsening mental health regardless of employment status for Japanese workers.
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http://dx.doi.org/10.1177/00207640211017586DOI Listing
May 2021

Oncological issues in staging mediastinal lymph node metastases in left lung cancer.

Asian J Surg 2021 Apr 30. Epub 2021 Apr 30.

Department of General Thoracic Surgery, Southern Tohoku General Hospital, Research Institute for Neuroscience & Respirology, Koriyama, Japan.

Objective: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL).

Methods: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy.

Results: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis.

Conclusions: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.
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http://dx.doi.org/10.1016/j.asjsur.2021.04.003DOI Listing
April 2021

Port placement in robotic thoracic surgery for inferior mediastinal tumors.

Ann Thorac Surg 2021 Apr 27. Epub 2021 Apr 27.

Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.

Robotic surgery for inferior mediastinal tumors located below the inferior vein is rare. The difficulty of resection varies depending on port placement and approach, especially on the left side. Considering that we have tried three different approaches for left inferior mediastinal tumors, we identify the advantages and disadvantages of each method. The approach from three arms and one assist placed on the ventral side of the inferior angle of the scapula is the best access for inferior mediastinal tumors. If the Si system is used, the patient cart should approach from the caudal side and dock on the dorsal side.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.044DOI Listing
April 2021

Survival of Octogenarians with Early-Stage Non-small Cell Lung Cancer is Comparable Between Wedge Resection and Lobectomy/Segmentectomy: JACS1303.

Ann Surg Oncol 2021 Apr 26. Epub 2021 Apr 26.

Department of General Thoracic Surgery, Dokkyo Medical University, Shimotsuga, Japan.

Background: Anatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC.

Methods: The study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016.

Results: The 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6-93.0 % vs 83.7 % 95 % CI, 74.0-90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39-1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8-95.9 % vs 75.8 %; 95 % CI, 62.0-85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079).

Conclusions: Wedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy.
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http://dx.doi.org/10.1245/s10434-021-09835-wDOI Listing
April 2021

Analysis of Gait Motion Changes by Intervention Using Robot Suit Hybrid Assistive Limb (HAL) in Myelopathy Patients After Decompression Surgery for Ossification of Posterior Longitudinal Ligament.

Front Neurorobot 2021 31;15:650118. Epub 2021 Mar 31.

Department of Orthopaedic Surgery, University of Tsukuba, Tsukuba, Japan.

Ossification of the posterior longitudinal ligament (OPLL) is a hyperostonic condition in which the posterior longitudinal ligament becomes thick and loses its flexibility, resulting in ectopic ossification and severe neurologic deficit (Matsunaga and Sakou, 2012). It commonly presents with myelopathy and radiculopathy and with myelopathy progression motor disorders and balance disorders can appear. Even after appropriate surgical decompression, some motor impairments often remain. The Hybrid Assistive Limb (HAL) is a wearable powered suit designed to assist and support the user's voluntary control of hip and knee joint motion by detecting bioelectric signals from the skin surface and force/pressure sensors in the shoes during movement. In the current study, the HAL intervention was applied to 15 patients diagnosed with OPLL who presented with myelopathy after decompression surgery (6 acute and 9 chronic stage). Following the HAL intervention, there were significant improvements in gait speed, cadence, stride length, in both acute and chronic groups. Joint angle analysis of the lower limbs showed that range of motion (ROM) of hip and knee joints in acute group, and also ROM of hip joint and toe-lift during swing in chronic group increased significantly. ROM of knee joint became closer to healthy gait in both groups. Electromyography analysis showed that hamstrings activity in the late swing phase increased significantly for acute patients. Immidiate effect from HAL session was also observed. EMG of vastus medialis were decreased except chronic 7th session and EMG of gastrocnemius were decreased except acute 7th session, which suggests the patients were learning to walk with lesser knee-hypertension during the sessions. After all, double knee action appeared in both acute and chronic groups after the HAL intervention, rather than knee hyper-extension which is a common gait impairment in OPLL. We consider that these improvements lead to a smoother and healthier gait motion.
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http://dx.doi.org/10.3389/fnbot.2021.650118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044802PMC
March 2021

Interscan measurement error of knee cartilage thickness and projected cartilage area ratio at 9 regions and 45 subregions by fully automatic three-dimensional MRI analysis.

Eur J Radiol 2021 Jun 8;139:109700. Epub 2021 Apr 8.

Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Japan. Electronic address:

Background: We have developed a fully automatic three-dimensional MRI analysis software program for automatic segmentation of knee cartilage using a deep neural network. The purpose of this study was to use this software to clarify the interscan measurement error of the knee cartilage thickness and projected cartilage area ratio at 9 regions and 45 subregions in the knee.

Methods: Ten healthy volunteers underwent MRI twice in the same day. The software provided cartilage thickness and projected cartilage area ratio (thickness ≥ 1.5 mm) at 9 regions and 45 subregions of the knee without any manual correction. The interscan measurement error was calculated at each region and subregion from the data of nine donors, except for one donor who had body motion during the MRI examination.

Results: The interscan measurement error of cartilage thickness was less than 0.10 mm at all 9 regions and at 39 subregions among 45 subregions. The measurement errors ranged from 0.03 to 0.21 mm. The intraclass correlation coefficients (ICC) of cartilage thickness were higher than 0.75 at all 9 regions and 41 subregions. The interscan measurement error of the projected cartilage area ratio ranged from 0.01 to 0.03 for all 9 regions.

Conclusions: This study clarified the interscan measurement error of the knee cartilage thickness and projected cartilage area ratio.
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http://dx.doi.org/10.1016/j.ejrad.2021.109700DOI Listing
June 2021

Isolation and characterisation of lymphatic endothelial cells from lung tissues affected by lymphangioleiomyomatosis.

Sci Rep 2021 Apr 16;11(1):8406. Epub 2021 Apr 16.

Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 Hongo; Bunkyoku, Tokyo, 113-8431, Japan.

Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease characterised by the proliferation of smooth muscle-like cells (LAM cells), and an abundance of lymphatic vessels in LAM lesions. Studies reported that vascular endothelial growth factor-D (VEGF-D) secreted by LAM cells contributes to LAM-associated lymphangiogenesis, however, the precise mechanisms of lymphangiogenesis and characteristics of lymphatic endothelial cells (LECs) in LAM lesions have not yet been elucidated. In this study, human primary-cultured LECs were obtained both from LAM-affected lung tissues (LAM-LECs) and normal lung tissues (control LECs) using fluorescence-activated cell sorting (FACS). We found that LAM-LECs had significantly higher ability of proliferation and migration compared to control LECs. VEGF-D significantly promoted migration of LECs but not proliferation of LECs in vitro. cDNA microarray and FACS analysis revealed the expression of vascular endothelial growth factor receptor (VEGFR)-3 and integrin α9 were elevated in LAM-LECs. Inhibition of VEGFR-3 suppressed proliferation and migration of LECs, and blockade of integrin α9 reduced VEGF-D-induced migration of LECs. Our data uncovered the distinct features of LAM-associated LECs, increased proliferation and migration, which may be due to higher expression of VEGFR-3 and integrin α9. Furthermore, we also found VEGF-D/VEGFR-3 and VEGF-D/ integrin α9 signaling play an important role in LAM-associated lymphangiogenesis.
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http://dx.doi.org/10.1038/s41598-021-88064-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052438PMC
April 2021

Prognostic impact of extranodal extension in patients with pN1-N2 lung adenocarcinoma.

J Cancer Res Clin Oncol 2021 Apr 2. Epub 2021 Apr 2.

Department of Pathology and Clinical Laboratories, National Cancer Center, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

Purpose: Lymph node involvement is one of the important prognostic factors of patients with lung adenocarcinoma. In the tumor, node, and metastasis classification, lymph node involvement is categorized only according to the anatomical station and not the involvement pattern. The aim of this study was to investigate which morphological pattern of lymph node involvement affects the prognosis of patients with surgically resected lung adenocarcinoma.

Methods: We retrospectively reviewed 168 consecutive patients who underwent surgical resection for primary lung adenocarcinoma with lymph node involvement. The morphological patterns of lymph node involvement (tumor area, number of metastatic lymph nodes, presence of necrosis, and extranodal extension) were histologically examined. The relationships between the patterns of lymph node involvement, clinicopathological features, and survival of patients were analyzed.

Results: Eighty patients had N1 disease, and 88 patients had N2 disease. Univariate analysis revealed that invasive size, history of adjuvant chemotherapy, and presence of extranodal extension were significant prognostic factors in N1 patients, and vascular invasion, pleural invasion, presence of epidermal growth factor receptor mutation, history of adjuvant chemotherapy, and presence of extranodal extension were significant prognostic factors in N2 patients. In a bivariate analysis including other clinicopathological factors and patterns of lymph node involvement, the presence of extranodal extension was significantly associated with poor 3-year overall and recurrence-free survival of both N1 and N2 patients.

Conclusions: In patients who underwent surgical resection for lung adenocarcinoma with lymph node involvement, the extranodal extension was the most important prognostic factor among morphological lymph node involvement patterns.
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http://dx.doi.org/10.1007/s00432-021-03608-4DOI Listing
April 2021

Left pneumonectomy for primary lung cancer with Trousseau's syndrome.

BMJ Case Rep 2021 Mar 22;14(3). Epub 2021 Mar 22.

General Thoracic Surgery, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan.

Trousseau's syndrome is a paraneoplastic syndrome and a pathological condition that causes cerebral stroke symptoms due to hypercoagulation associated with malignant tumours. There have been many cases of advanced lung cancer, but few reports have described surgery for lung cancer with Trousseau's syndrome. We encountered a 76-year-old man suspected of having Trousseau's syndrome associated with lung cancer. He was transferred to our hospital on the second day after the onset. After admission, he was treated with heparin and edaravone, and his condition improved. On the 12th day after the onset, we performed left pneumonectomy and lymph node dissection (ND2a-2). The final pathological results were adenocarcinoma, pathological stage was T4 (tumour size: 77 mm, pulmonary artery invasion) N1(#11, #12u) M0, stage IIIA. He has been recurrence free for 23 months since the surgery. In the future, we need to follow his condition carefully.
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http://dx.doi.org/10.1136/bcr-2020-240927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986757PMC
March 2021

Extent of mediastinal nodal dissection in stage I non-small cell lung cancer with a radiological pure-solid appearance.

Eur J Surg Oncol 2021 Jul 12;47(7):1797-1804. Epub 2021 Mar 12.

Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.

Background: Radiological pure-solid lung cancer denotes a high invasive nature compared to one that is part-solid. Mediastinal lymph nodal dissection (mLND) is a standard surgical procedure for nodal management in lung cancer surgery, however, the prognostic impact of the extent of mLND in pure-solid lung cancer is still unknown.

Methods: We reviewed 459 patients with c-stage I radiological pure-solid lung cancer that underwent pulmonary lobectomy with mLND. Pure-solid was defined as a tumor showing only a consolidation without any ground glass opacity. The extent of mLND was classified into lobe-specific (L-mLND) and systematic (S-mLND). Prognostic significance of mLND was assessed by a multivariable analysis using propensity-score matching. Survivals were calculated by Kaplan-Meier methods using log-rank test.

Results: Pathological nodal metastasis was found in 127 (27.6%) patients (hilar: 52 (11.3%), mediastinal: 75 (16.3%)). L-mLND was performed in 278 (61%) patients. A multivariable analysis did not show the survival difference for the extent of mLND (p = 0.266). The 5-year overall survival (OS) was not significantly different between S-mLND and L-mLND (74.3% vs. 72.7%, p = 0.712), which was similar even in 114 propensity-score matched pairs (78.8% vs. 79.9%, p = 0.665). While S-mLND showed a trend for survival benefit compared to L-mLND provided that the tumor showed higher standardized uptake value (SUVmax) (5y-OS: 70.0% vs. 59.2%, p = 0.093).

Conclusions: Prognostic impact of L-mLND was similar to S-mLND in c-stage I radiological pure-solid lung cancers in the propensity-score matched comparison. Among them, higher SUVmax value might be a promising indicator to decide the extent of mediastinal lymphadenectomy.
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http://dx.doi.org/10.1016/j.ejso.2021.03.232DOI Listing
July 2021

Preoperative nivolumab to evaluate pathological response in patients with stage I non-small cell lung cancer: a study protocol of phase II trial (POTENTIAL).

BMJ Open 2021 03 17;11(3):e043234. Epub 2021 Mar 17.

Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.

Introduction: Recently, inhibition of programmed cell death 1 or its ligand has shown therapeutic effects on non-small cell lung cancer (NSCLC). However, the effectiveness of preoperative nivolumab monotherapy for stage I NSCLC remains unknown. The present study aimed to investigate the pathological response of preoperative treatment with nivolumab for clinically node negative but having a high risk of NSCLC recurrence.

Methods And Analysis: The Preoperative Nivolumab (Opdivo) to evaluate pathologic response in patients with stage I non-small cell lung cancer: a phase 2 trial (POTENTIAL) study is a multicentre phase II trial investigating efficacy of preoperative nivolumab for clinical stage I patients at high risk of recurrence. This study includes histologically or cytologically confirmed NSCLC patients with clinical N0 who were found on preoperative high-resolution CT to have a pure solid tumour without a ground-glass opacity component (clinical T1b, T1c or T2a) or a solid component measuring 2-4 cm in size (clinical T1c or T2a). Patients with epidermal growth factor receptor (EGFR) mutation (deletion of exon 19 or point mutation on exon21, L858R), anaplastic lymphoma kinase (ALK) translocation or c-ros oncogene 1 (ROS-1) translocation are excluded from this study. Nivolumab (240 mg/body) is administrated intravenously as preoperative therapy every 2 weeks for three cycles. Afterward, lobectomy and mediastinal lymph node dissection (ND 2a-1 or ND 2a-2) are performed. The primary endpoint is a pathological complete response in the resected specimens. The secondary endpoints are safety, response rates and major pathological response. The planed sample size is 50 patients. Patients have been enrolled since April 2019.

Ethics And Dissemination: This trial was approved by the Institutional Review Board of Hiroshima University Hospital and other participating institutions. This trial will help examine the efficacy of preoperative nivolumab therapy for clinical stage I NSCLC.

Trial Registration Number: jRCT2061180016.
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http://dx.doi.org/10.1136/bmjopen-2020-043234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978092PMC
March 2021

Cancer-associated fibroblast migration in non-small cell lung cancers is modulated by increased integrin α11 expression.

Mol Oncol 2021 May 25;15(5):1507-1527. Epub 2021 Mar 25.

Division of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, Tokyo, Japan.

Cancer-associated fibroblasts (CAFs) regulate cancer progression through the modulation of extracellular matrix (ECM) and cancer cell adhesion. While undergoing a series of phenotypic changes, CAFs control cancer-stroma interactions through integrin receptor signaling. Here, we isolated CAFs from patients with non-small-cell lung cancer (NSCLC) and examined their gene expression profiles. We identified collagen type XI α1 (COL11A1), integrin α11 (ITGA11), and the ITGA11 major ligand collagen type I α1 (COL1A1) among the 390 genes that were significantly enriched in NSCLC-associated CAFs. Increased ITGA11 expression in cancer stroma was correlated with a poor clinical outcome in patients with NSCLC. Increased expression of fibronectin and collagen type I induced ITGA11 expression in CAFs. The cellular migration of CAFs toward collagen type I and fibronectin was promoted via ERK1/2 signaling, independently of the fibronectin receptor integrin α5β1. Additionally, ERK1/2 signaling induced ITGA11 and COL11A1 expression in cancer stroma. We, therefore, propose that targeting ITGA11 and COL11A1 expressing CAFs to block cancer-stroma interactions may serve as a novel, promising anti-tumor strategy.
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http://dx.doi.org/10.1002/1878-0261.12937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096795PMC
May 2021

Pulmonary arterial sarcoma with a wide range of endovascular intima invasion microscopically.

Ann Thorac Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of General Thoracic Surgery, Juntendo University Hospital, Tokyo, Japan.

A 69-year-old man underwent right middle and lower lobectomy for suspected lung cancer (cT3N1M0). The final pathological diagnosis was pulmonary artery sarcoma (PAS). The stump was positive despite having a sufficient surgical margin. After 11 months, we performed completion pneumonectomy and pulmonary artery (PA) resection and replacement under extracorporeal circulation for local recurrence. Although the PA was macroscopically intact, the frozen pathological diagnosis was positive three times. Since PAS extends microscopically through the intima of the PA, it is difficult to determine the extent of resection on imaging. We consider confirmation by a frozen pathological diagnosis to be essential.
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http://dx.doi.org/10.1016/j.athoracsur.2021.02.006DOI Listing
February 2021

Discovery of Carbono(di)thioates as Indoleamine 2,3-Dioxygenase 1 Inhibitors.

ACS Med Chem Lett 2021 Feb 15;12(2):211-216. Epub 2021 Jan 15.

Laboratory of Medicinal Chemistry, Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1 Nakano-machi, Hachi-oji, Tokyo 192-0015, Japan.

A structure-activity relationship study unexpectedly showed that carbonothioates and , obtained by a unique alkaline hydrolysis of 2-alkylthio-oxazolines and , respectively, are a novel scaffold for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. Derivatization of the carbonothioates enhanced inhibitory activity against IDO1 and cellular kynurenine production without cytotoxicity and led to the discovery of the related scaffolds carbonodithioates and cyanocarbonimidodithioates as IDO1 inhibitors. Incorporation of an OH group provided the most potent analogue . UV-visible absorption spectroscopy of the Soret band, as well as docking and peptide mapping studies, suggested that these molecules bind to the heme in the active site of IDO1. Our unique IDO1 inhibitors are potential leads for future development.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883372PMC
February 2021

Preoperative cumulative smoking dose on lung cancer surgery in a Japanese nationwide database.

Ann Thorac Surg 2021 Feb 15. Epub 2021 Feb 15.

Department of General Thoracic Surgery, Dokkyo Medical University, Tochigi, Japan.

Background: Smoking is a known risk factor for postoperative mortality and morbidity. However, the significance of cumulative smoking dose in preoperative risk assessment has not been established. We examined the influence of preoperative cumulative smoking dose on surgical outcomes after lobectomy for primary lung cancer.

Methods: A total of 80,989 patients with primary lung cancer undergoing lobectomy from 2014 to 2016 were enrolled. Preoperative cumulative smoking dose was categorized by pack-years (PY): Non-smokers, PY = 0; Light smokers, 0 < PY < 10; Moderate smokers, 10 ≤ PY < 30; and Heavy smokers, 30 ≤ PY. The risk of short-term outcomes was assessed according to PY by multivariable analysis adjusted for other covariates.

Results: Postoperative 30-day mortality, as well as pulmonary, cardiovascular, and infectious complications, increased with preoperative PY. Multivariable analysis revealed the odds ratios (ORs) for postoperative mortality compared with non-smokers were 1.76 for light smokers (p=0.044), 1.60 for moderate smokers (p=0.026), and 1.73 for heavy smokers (p=0.003). The ORs for pulmonary complications compared with non-smokers were 1.20 for light smokers (p= 0.022), 1.40 for moderate smokers (p<0.001), and 1.72 for heavy smokers (p<0.001). Heavy smokers had a significantly increased risk of postoperative cardiovascular (OR, 1.26; p=0.002) and infectious complications (OR, 1.39; p=0.007) compared with non-smokers.

Conclusions: The risk of mortality and morbidity after lung resection could be predicted according to preoperative cumulative smoking dose. These findings contribute to the development of strategies in perioperative management of lung resection patients.
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http://dx.doi.org/10.1016/j.athoracsur.2021.01.055DOI Listing
February 2021

Psychological impact of the state of emergency over COVID-19 for non-permanent workers: a Nationwide follow-up study in Japan.

BMC Public Health 2021 02 11;21(1):334. Epub 2021 Feb 11.

Center for Clinical Epidemiology and Health Technology Assessment, St. Luke's International University, OMURA Susumu & Mieko Memorial St. Luke's Center for Clinical Academia, 5th Floor 3-6-2 Tsukiji Chuo-ku, Tokyo, 104-0045, Japan.

Background: The outbreak of COVID-19 has caused mental health problems and increased unemployment due to the economic recession. This survey aimed to assess the psychological impact of the state of emergency. We estimated changes in mental health, quality of life, and unemployment experience for general workers during the first COVID-19 outbreak in Japan.

Methods: We conducted a nationwide follow-up study. During the periods of March 26 to April 6, 2020 and June 26 to July 2, 2020, we used the internet to survey general workers aged 15 to 59 years in Japan. The questionnaire items covered employment status and socioeconomic factors, and we used the Center for Epidemiologic Studies Depression Scale (CES-D) and EQ-5D-5L to assess depression and health-related quality of life (HR-QOL), respectively. The differences in outcomes of permanent and non-permanent workers were analyzed using propensity score analysis. A multiple linear regression analysis was performed to examine the relationship between unemployment and CES-D scores.

Results: We included 2351 subjects in the analysis. Changes in both CES-D scores and utility were not significantly different between the two groups. However, a significant difference was found regarding the rate of unemployment, which was associated with higher CES-D scores.

Conclusions: The present study demonstrated that the mental health of non-permanent workers was not negatively affected following the state of emergency due to COVID-19 in Japan. Unemployment is an important factor that influences the mental health of general workers.
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http://dx.doi.org/10.1186/s12889-021-10401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877331PMC
February 2021

Clinical impact of a small component of ground-glass opacity in solid-dominant clinical stage IA non-small cell lung cancer.

J Thorac Cardiovasc Surg 2020 Dec 29. Epub 2020 Dec 29.

Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan. Electronic address:

Objective: Non-small cell lung cancers with a ground-glass opacity component have better prognosis than those with solid nodules of equivalent consolidation size. However, the impact of small ground-glass opacity components on prognosis is unknown. Therefore, we aimed to evaluate the significance of a small ground-glass opacity component in solid-dominant clinical stage IA non-small cell lung cancers.

Methods: We reviewed the cases of 543 surgically resected solid-dominant c-stage IA non-small cell lung cancers, which was defined as a tumor with consolidation tumor ratio of 0.75 or more on computed tomography. The patients were classified into 2 groups: 0.75 or less consolidation tumor ratio less than 1 (n = 126) and consolidation tumor ratio of 1 (n = 417). The prognoses were compared between the 2 groups.

Results: Among the 543 cases, multivariable analyses revealed that pure-solid appearance was a predictor of worse overall survival (hazard ratio, 2.051; 95% confidence interval, 1.044-4.028). Compared with the part-solid group, the pure-solid group was associated with poor survival in c-stages IA2 (5-year overall survival: 91.5% vs 76.8%, hazard ratio, 2.942; 95% confidence interval, 1.402-6.173; recurrence-free survival: 89.0% vs 68.8%, hazard ratio, 3.439; 95% confidence interval, 1.776-6.669) and IA3 (5-year overall survival: 93.5% vs 63.0%, hazard ratio, 5.110; 95% confidence interval, 1.607-16.241; recurrence-free survival: 80.5% vs 54.1%, hazard ratio, 2.789; 95% confidence interval, 1.290-6.027). The T categories significantly affected 5-year overall survival only in the pure-solid group (cT1a, 89.3%; cT1b, 76.8%; cT1c, 63.0%).

Conclusions: A small ground-glass opacity component has an impact on the prognosis of patients with solid-dominant c-stage IA non-small cell lung cancer. Therefore, c-stage IA non-small cell lung cancers should be evaluated separately for tumors with ground-glass opacity and pure-solid tumors.
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http://dx.doi.org/10.1016/j.jtcvs.2020.12.089DOI Listing
December 2020

Certified thoracic surgeons in Japan: a national database survey on risk-adjusted mortality associated with lung resection.

Surg Today 2021 Jan 30. Epub 2021 Jan 30.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Purpose: We investigated the association between the number of certified general thoracic surgeons (GTSs) and the mortality after lung cancer surgery, based on the data from the National Clinical Database (NCD).

Methods: We analyzed the characteristics and operative and postoperative data of 120,946 patients who underwent lung cancer surgery in one of the 905 hospitals in Japan. The number of GTSs in each hospital was categorized as 0, 1-2, or 3 or more. Multivariable analysis was applied to adjust the patients' preoperative risk factors, as identified in a previous study. We calculated 95% confidence intervals (CI) for the mortality rate based on the odds ratios (ORs).

Results: The patients' characteristics were distributed almost uniformly regardless of the number of GTSs. Crude mortality according to the number of GTSs of 0, 1-2, or 3 or more was 0.9%, 0.8%, and 0.7%, respectively (p = 0.03). However, after adjustment, the ORs for 1-2 and 3 or more GTSs (reference: 0) were 0.86 (p = 0.23, 95% CI: 0.67-1.10) and 0.84 (p = 0.18, 95% CI: 0.64-1.09), respectively. The number of GTSs did not have a significant association with mortality. Similar results were observed for patients in the lobectomy cohort.

Conclusion: Low surgical mortality was consistent, regardless of the number of GTSs in each hospital.
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http://dx.doi.org/10.1007/s00595-021-02227-3DOI Listing
January 2021

Predicting pathological lymph node status in clinical stage IA peripheral lung adenocarcinoma.

Eur J Cardiothorac Surg 2021 Jan 30. Epub 2021 Jan 30.

Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.

Objectives: Even with current diagnostic technology, it is difficult to accurately predict pathological lymph node status (PLNS). This study aimed to develop a prediction model of PLNS in peripheral adenocarcinoma with a dominant solid component, based on clinical and radiological factors on thin-section computed tomography, to identify patients to whom wedge resection or other local therapies could be applied.

Methods: Of 811 patients enrolled in a prospective multi-institutional study (JCOG0201), 420 patients with clinical stage IA peripheral lung adenocarcinoma having a dominant solid component were included. Multivariable logistic regression was performed to develop a model based on clinical and centrally reviewed radiological factors. Leave-one-out cross-validation and external validation analyses were performed, using independent data from 221 patients. Sensitivity, specificity and concordance statistics were calculated to evaluate diagnostic performance.

Results: The formula for calculating the probability of pathological lymph node metastasis included the following variables: tumour diameter (including ground-glass opacity), consolidation-to-tumour ratio and density of solid component. The concordance statistic was 0.8041. When the cut-off value associated with the risk of incorrectly predicting negative pathological lymph node metastasis (pN-) was 4.9%, diagnostic sensitivity and specificity in predicting PLNS were 95.7% and 46.0%, respectively. The concordance statistic for the external validation set was 0.7972, and diagnostic sensitivity and specificity in predicting PLNS were 95.4% and 40.5%, respectively.

Conclusions: The proposed model is clinically useful and successfully predicts pN- in patients with clinical stage IA peripheral lung adenocarcinoma with a dominant solid component.
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http://dx.doi.org/10.1093/ejcts/ezaa478DOI Listing
January 2021

Surgical challenges in multimodal treatment of N2-stage IIIA non-small cell lung cancer.

Jpn J Clin Oncol 2021 Mar;51(3):333-344

Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.
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http://dx.doi.org/10.1093/jjco/hyaa249DOI Listing
March 2021

Carinal resection and double-barrel reconstruction following oesophagectomy for oesophageal carcinoma with broncho-oesophageal fistula.

Interact Cardiovasc Thorac Surg 2021 Apr;32(3):489-491

Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.

A 54-year-old man presenting with dysphagia was diagnosed with locally advanced oesophageal carcinoma with a broncho-oesophageal fistula (c-T4bN2M0 stage IVa). Concurrent chemoradiotherapy (60 Gy) was planned; however, bleeding from the oesophageal lesions progressed during chemoradiotherapy (16 Gy). Oesophagectomy with carinal resection and double-barrelled reconstruction was performed. Despite the inevitable recurrent nerve palsy and a minor fistula at the tracheal anastomosis, he recovered with conservative treatment and was discharged 4 months after the salvage surgery. He is alive without recurrence 28 months after the surgery.
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http://dx.doi.org/10.1093/icvts/ivaa279DOI Listing
April 2021

Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation.

Heliyon 2021 Jan 5;7(1):e05888. Epub 2021 Jan 5.

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.

Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803657PMC
January 2021

A single-arm study of sublobar resection for ground-glass opacity dominant peripheral lung cancer.

J Thorac Cardiovasc Surg 2020 Nov 12. Epub 2020 Nov 12.

Division of Thoracic Surgery, Keio University School of Medicine, Tokyo, Japan.

Background: The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown.

Methods: We conducted a single-arm confirmatory trial to evaluate the efficacy and safety of sublobar resection for ground-glass opacity dominant peripheral lung cancer. Lung cancer with maximum tumor diameter 2.0 cm or less and with consolidation tumor ratio 0.25 or less based on thin-section computed tomography were registered. The primary end point was 5-year relapse-free survival. The planned sample size was 330 with the expected 5-year relapse-free survival of 98%, threshold of 95%, 1-sided α of 5%, and power of 90%. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number University Hospital Medical Information Network 000002008.

Results: Between May 2009 and April 2011, 333 patients were enrolled from 51 institutions. Median age was 62 years (interquartile range, 56-68), and 109 were smokers. Median maximum tumor diameter was 1.20 cm (1.00-1.54). Median maximum tumor diameter of consolidation was 0 (0.00-0.20). The primary end point, 5-year relapse-free survival, was estimated on 314 patients who underwent sublobar resection. Operative modes were 258 wide wedge resections and 56 segmentectomies. Median pathological surgical margin was 15 mm (0-55). The 5-year relapse-free survival was 99.7% (90% confidence interval, 98.3-99.9), which met the primary end point. There was no local relapse. Grade 3 or higher postoperative complications based on Common Terminology Criteria for Adverse Effect v3.0 were observed in 17 patients (5.4%), without any grade 4 or 5.

Conclusions: Sublobar resection with enough surgical margin offered sufficient local control and relapse-free survival for lung cancer clinically resectable N0 staged by computed tomography with 3 or fewer peripheral lesions 2.0 cm or less amenable to sublobar resection and with a consolidation tumor ratio of 0.25 or less.
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http://dx.doi.org/10.1016/j.jtcvs.2020.09.146DOI Listing
November 2020

Salvage surgery for non-small cell lung cancer after tyrosine kinase inhibitor treatment.

Lung Cancer 2021 03 10;153:108-116. Epub 2021 Jan 10.

Department of General Thoracic Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.

Objectives: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting.

Methods: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS.

Results: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery.

Conclusion: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.
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http://dx.doi.org/10.1016/j.lungcan.2020.12.037DOI Listing
March 2021