Publications by authors named "Kenji Kimura"

95 Publications

Cluster analysis of emphysema for predicting pulmonary complications after thoracoscopic lobectomy.

Eur J Cardiothorac Surg 2021 May 19. Epub 2021 May 19.

Division of Chest Surgery, Hyogo Cancer Center, Akashi, Japan.

Objectives: Despite significant advances in surgical techniques, including thoracoscopic approaches and perioperative care, the morbidity rate remains high after lung resection. This study focused on a low attenuation cluster analysis, which represented the size distribution of pulmonary emphysema and assessed its utility for predicting postoperative pulmonary complications after thoracoscopic lobectomy.

Methods: From April 2013 to September 2018, lung cancer patients who received spirometry and computed tomography (CT) before surgery and underwent thoracoscopic lobectomy were included. The cumulative size distribution of the low attenuation area (LAA, defined as ≤-950 Hounsfield unit on CT) clusters followed a power-law characterized by an exponent D-value, a measure of the complexity of the alveolar structure. D-value and LAA% (LAA/total lung volume) were calculated using preoperative 3-dimensional CT software. The relationship between pulmonary complications and patient characteristics, including D-value and LAA%, was investigated.

Results: Among 471 patients, there were 61 respiratory complication cases (12.9%). Receiver operation characteristic curve analysis revealed that the best predictive cut-off value of D-value and LAA% for pulmonary complications was 2.27 and 16.5, respectively, with an area under the curve of 0.72 and 0.58, respectively. D-value was significantly correlated with % forced expiratory volume in 1 s. Per univariate analysis, gender, smoking history, forced expiratory volume in 1 s/forced vital capacity, LAA% and D-value were risk factors for predicting postoperative pulmonary complications. In the multivariate analysis, D-value remained a significant predictive factor.

Conclusion: Preoperative assessment of emphysema cluster analysis may represent the vulnerability of the operated lung and could be the novel predictor for pulmonary complications after thoracoscopic lobectomy.
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http://dx.doi.org/10.1093/ejcts/ezab237DOI Listing
May 2021

Staircase array of inclined refractive multi-lenses for large field of view pixel super-resolution scanning transmission hard X-ray microscopy.

J Synchrotron Radiat 2021 May 12;28(Pt 3):732-740. Epub 2021 Mar 12.

Institute of Microstructure Technology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Baden-Württemberg, Germany.

Owing to the development of X-ray focusing optics during the past decades, synchrotron-based X-ray microscopy techniques allow the study of specimens with unprecedented spatial resolution, down to 10 nm, using soft and medium X-ray photon energies, though at the expense of the field of view (FOV). One of the approaches to increase the FOV to square millimetres is raster-scanning of the specimen using a single nanoprobe; however, this results in a long data acquisition time. This work employs an array of inclined biconcave parabolic refractive multi-lenses (RMLs), fabricated by deep X-ray lithography and electroplating to generate a large number of long X-ray foci. Since the FOV is limited by the pattern height if a single RML is used by impinging X-rays parallel to the substrate, many RMLs at regular intervals in the orthogonal direction were fabricated by tilted exposure. By inclining the substrate correspondingly to the tilted exposure, 378000 X-ray line foci were generated with a length in the centimetre range and constant intervals in the sub-micrometre range. The capability of this new X-ray focusing device was first confirmed using ray-tracing simulations and then using synchrotron radiation at BL20B2 of SPring-8, Japan. Taking account of the fact that the refractive lens is effective for focusing high-energy X-rays, the experiment was performed with 35 keV X-rays. Next, by scanning a specimen through the line foci, this device was used to perform large FOV pixel super-resolution scanning transmission hard X-ray microscopy (PSR-STHXM) with a 780 ± 40 nm spatial resolution within an FOV of 1.64 cm × 1.64 cm (limited by the detector area) and a total scanning time of 4 min. Biomedical implant abutments fabricated via selective laser melting using Ti-6Al-4V medical alloy were measured by PSR-STHXM, suggesting its unique potential for studying extended and thick specimens. Although the super-resolution function was realized in one dimension in this study, it can be expanded to two dimensions by aligning a pair of presented devices orthogonally.
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http://dx.doi.org/10.1107/S1600577521001521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127365PMC
May 2021

Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated with Atypical Thymic Carcinoid: A Case Report.

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

Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.
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http://dx.doi.org/10.5761/atcs.cr.20-00354DOI Listing
April 2021

Sulfoquinovosylglyceryl ether, a new group of ether lipids from lake ball-forming green alga Aegagropilopsis moravica (family Pithophoraceae).

Chem Asian J 2021 Jun 3;16(11):1493-1498. Epub 2021 May 3.

Research Center for Biotechnology and Pharmaceutical Engineering and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.

Ether lipids are a minor group of glycerolipids but widespread in nature, playing a vital function as membrane lipids, signalling molecules, or buoyant material. We have discovered sulfoquinovosylchimyl alcohol (1), a sulfonate-substituted glyceroglycolipid, from a lake ball-forming green alga Aegagropilopsis moravica (family Pithophoraceae), with the guidance of antimicrobial activity. The structure of 1, including absolute configurations of all sterogenic centers, was established by extensive NMR analysis, chemical degradation studies, and finally by total synthesis. Lipid 1 is an ether variant of a lyso-form of sulfoquinovosyldiacylglycerol, a chloroplast-specific membrane lipid, and thus represents a new lipid class, sulfoquinovosylglyceryl ether. A high occurrence of mobile life form in the family Pithophoraceae and a unique behaviour of chloroplasts reported in closely related Aegagropila linnaei, the famous lake-ball alga, implies a possible role of lipid 1 or its acyl derivatives in ecological adaptation to dysphotic niches.
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http://dx.doi.org/10.1002/asia.202100278DOI Listing
June 2021

Debulking surgery for functional pleural dissemination of parathyroid carcinoma-case report.

J Cardiothorac Surg 2021 Apr 15;16(1):86. Epub 2021 Apr 15.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2-L5, Yamadaoka, Suita, 565-0871, Osaka, Japan.

Background: A rare cause of primary hyperparathyroidism (PHPT) is a parathyroid carcinoma. Hypercalcemia with an elevated parathyroid hormone (PTH) level seen in recurrent and metastasis disease cases is often refractory to medical therapy, thus surgical resection is recommended when possible. We performed debulking surgery for pleural dissemination of parathyroid cancer for improvement of symptoms in a patient with hypercalcemia.

Case Presentation: A 30-year-old male with hypercalcemia was diagnosed with parathyroid cancer. Following surgery, intact PTH level elevation and hypercalcemia progression due to recurrent disease were noted. An active status of functional left pleural dissemination was revealed in 99mTc-methoxyisobutylisonitrile and somatostatin receptor scintigraphy results, but not in the area of pulmonary metastasis, and debulking surgery was performed. Thereafter, the PTH level was decreased temporarily and activities of daily living improved.

Conclusion: Aggressive resection of metastatic disease in patients with a parathyroid carcinoma is taken into consideration to control hypercalcemia.
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http://dx.doi.org/10.1186/s13019-021-01477-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048281PMC
April 2021

Importance of the preoperative prognostic nutritional index score as a predictor of chronic lung allograft dysfunction after lung transplantation: a Japanese single-institution study.

Surg Today 2021 Apr 11. Epub 2021 Apr 11.

Department of General Thoracic Surgery, Osaka University, Osaka, 565-0871, Japan.

Purposes: Numerous indicators have been discussed as predictive markers for the incidence of chronic allograft dysfunction (CLAD) after lung transplantation (LTX). The aim of this study was to evaluate whether or not the preoperative prognostic nutrition index (PNI) correlated with the development of CLAD.

Method: This study is a single-center and retrospective cohort study. Forty-six patients underwent cadaveric lung transplantation between 2000 and 2016 at our institution. The primary endpoint of this study was the CLAD-free survival of the patients.

Result: CLAD was diagnosed in 11 patients (23%) during the follow-up period. Potential risk factors included recipient factors, donor factors, number of HLA mismatches, operation-related factors, and preoperative blood test results, including the preoperative PNI. The patients with a higher PNI showed a longer CLAD-free survival after LTX than those with lower values according to univariate and multivariate analyses (p = 0.01, 0.04, respectively). The 5-year CLAD-free survival rates in the higher-PNI patients and lower-PNI patients were 94% and 62%, respectively.

Conclusion: We found that a lower preoperative PNI of the recipient was significantly associated with a higher incidence rate of CLAD. The preoperative PNI may, therefore, be useful as a predictor of the development of CLAD.
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http://dx.doi.org/10.1007/s00595-021-02285-7DOI Listing
April 2021

Pleural invasion, epidermal growth factor receptor mutation and carcinoembryonic antigen level affect pleural lavage cytology-positive status in non-small-cell lung cancer.

Eur J Cardiothorac Surg 2021 Apr;59(4):791-798

Department of Thoracic Surgery, Hyogo Cancer Center, Akashi, Hyogo Prefecture, Japan.

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Objectives: Pleural invasion (pl) is strongly associated with the pleural lavage cytology (PLC) status. We analysed tumours with pl and evaluated the relationship between the PLC status and pl.

Methods: We retrospectively reviewed 428 surgically treated patients who had been diagnosed with non-small-cell lung cancer with pl and had their PLC status examined between 2000 and 2016. We investigated the influence of a PLC-positive status on the prognosis and searched for the factors predictive of a PLC-positive status.

Results: Seventy-eight (18%) patients were PLC positive. The recurrence-free survival of PLC-positive patients was significantly worse than that of PLC-negative patients in pl1 and pl2, but not in pl3 (5-year recurrence-free survival rate, PLC positive versus PLC negative: pl1, 22.0% vs 60.0%, P = 0.002; pl2, 30.4% vs 59.7%, P = 0.015; pl3, 50.0% vs 59.6%, P = 0.427). A multivariable analysis showed that the degree of pl (pl2-3 versus pl1) [odds ratio (OR) 5.34, P < 0.001] was an independent predictive factor for PLC positivity. Epidermal growth factor receptor (EGFR) mutation positivity (OR 5.48, P = 0.042) and carcinoembryonic antigen (CEA) ≥5 ng/ml (OR 3.78, P = 0.042) were associated with a PLC-positive status in patients with pl2-3. We found that the PLC-positive rate in patients with pl2-3 was 35.6%; however, if the tumour was EGFR mutation positive and had CEA ≥5 ng/ml, the PLC-positive rate increased to 77%.

Conclusions: If a tumour was suspected of being pl2-3 and had EGFR mutation positivity and CEA ≥5 ng/ml, the PLC-positive rate was extremely high.

Clinical Trial Registration Number: Hyogo Cancer Center, G-138.
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http://dx.doi.org/10.1093/ejcts/ezaa394DOI Listing
April 2021

Thymic Metastasis of Ovarian Cancer 33 Years After Primary Surgery.

Ann Thorac Surg 2021 05 30;111(5):e361-e363. Epub 2020 Oct 30.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

This report describes a case of an extremely late recurrence of thymic metastasis after radical resection of ovarian cancer. Chest computed tomography demonstrated anterior mediastinal nodules with a smooth marginal area in a 56-year-old woman who had undergone an oophorectomy for ovarian cancer 33 years earlier. Because imaging findings suggested a thymic epithelial tumor, a partial thymectomy was performed. Histopathologic results led to the diagnosis of thymic metastasis of ovarian cancer. In patients with a medical history of ovarian cancer, thymic metastasis should be considered in the differential diagnosis of thymic tumor.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.094DOI Listing
May 2021

A case of repeat resection for recurrent pulmonary metastasis from sebaceous gland carcinoma.

Surg Case Rep 2020 Aug 12;6(1):206. Epub 2020 Aug 12.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2 (L5), Yamadaoka, Suita, 565-0871, Japan.

Background: Sebaceous gland carcinoma (SGC) of the eyelid is an aggressive malignant eyelid tumor, and it can metastasize to the regional lymph nodes and distant organs. There have been only a few reported cases of patients who underwent pulmonary metastasectomy for metastatic SGC. We herein report a patient who underwent repeat pulmonary metastasectomies for recurrent pulmonary metastases from SGC.

Case Presentation: Bilateral small pulmonary nodules were detected in a 59-year-old woman with a history of eyelid SGC. She underwent wide wedge resection of the left lower lobe, and the disease was diagnosed as pulmonary metastases from SGC. Six months after the first pulmonary resection, CT showed that the nodules of right S2 and S10 had increased in size, and three small nodules had newly appeared in the right lung. The patient therefore underwent six wide wedge resections of the right lung through thoracotomy. After that, she underwent pulmonary metastasectomy 2 times. Ninety months after the first pulmonary resection, the patient is doing well without disease.

Conclusions: Given that a long-term survival was ultimately achieved in the present case, repeat pulmonary metastasectomy may be beneficial for recurrent pulmonary metastasis from SGC.
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http://dx.doi.org/10.1186/s40792-020-00947-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423815PMC
August 2020

Surgical management of thymic epithelial tumors.

Surg Today 2021 Mar 10;51(3):331-339. Epub 2020 Jul 10.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2-L5, Yamadaoka, Suita, Osaka, Japan.

Resection is the mainstay of treatment for thymic epithelial tumors (TETs), with complete removal of the tumor and involved organs being the ultimate aim. The choice of surgical approach plays a major role in defining treatment success, and the optimal choice of method should thus provide an adequate surgical view to achieve complete tumor resection. While median sternotomy is considered the gold standard for access to the mediastinum, several minimally invasive approaches to thymectomy have been described, including video-assisted robotic-assisted thymectomy, although the oncological outcomes of that procedure remain unclear. A multimodal approach incorporating chemotherapy or chemoradiotherapy followed by extended surgery may improve resectability and outcomes for patients with advanced TETs. Surgical debulking is also reportedly acceptable for invasive thymoma because of its potential for achieving favorable outcomes. Re-resection is an acceptable option for patients with recurrent thymoma after initial resection, and repeat resection for recurrent pleural dissemination seems effective. Here, the literature on current clinical practices in the surgical management and treatment of TETs is reviewed.
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http://dx.doi.org/10.1007/s00595-020-02070-yDOI Listing
March 2021

Effects of pirfenidone targeting the tumor microenvironment and tumor-stroma interaction as a novel treatment for non-small cell lung cancer.

Sci Rep 2020 07 2;10(1):10900. Epub 2020 Jul 2.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2-L5 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Targeting cancer-associated fibroblasts (CAFs), as well as the crosstalk between stroma and cancer cells, could be of value in managing cancers. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of fibroblast activation and the tumor-stroma interaction in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. PFD significantly inhibited myofibroblast differentiation and activation of both primary cultured normal human lung fibroblasts and CAFs. Cocultivation of NSCLC cells with conditioned media (CM) of fibroblasts changed the morphology or epithelial to mesenchymal transition (EMT) status, and PFD suppressed these changes. Cocultivation of CAFs with CM of NSCLC cells also induced activation of CAFs, and these changes were suppressed by PFD. On in vivo examination, CAFs promoted tumor progression, and PFD suppressed tumor progression with an inhibitory effect on tumor-stroma crosstalk. PFD might inhibit not only fibroblast activity, but also the crosstalk between cancer cells and fibroblasts. PFD may have great potential as a novel treatment for NSCLC from multiple perspectives.
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http://dx.doi.org/10.1038/s41598-020-67904-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331721PMC
July 2020

Cytoplasmic streaming drifts the polarity cue and enables posteriorization of the zygote at the side opposite of sperm entry.

Mol Biol Cell 2020 07 27;31(16):1765-1773. Epub 2020 May 27.

Cell Architecture Laboratory, Structural Biology Center, National Institute of Genetics, Mishima 411-8540, Japan.

Cell polarization is required to define body axes during development. The position of spatial cues for polarization is critical to direct the body axes. In zygotes, the sperm-derived pronucleus/centrosome complex (SPCC) serves as the spatial cue to specify the anterior-posterior axis. Approximately 30 min after fertilization, the contractility of the cell cortex is relaxed near the SPCC, which is the earliest sign of polarization and called symmetry breaking (SB). It is unclear how the position of SPCC at SB is determined after fertilization. Here, we show that SPCC drifts dynamically through the cell-wide flow of the cytoplasm, called meiotic cytoplasmic streaming. This flow occasionally brings SPCC to the opposite side of the sperm entry site before SB. Our results demonstrate that cytoplasmic flow determines stochastically the position of the spatial cue of the body axis, even in an organism like for which development is stereotyped.
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http://dx.doi.org/10.1091/mbc.E20-01-0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521852PMC
July 2020

A case of leiomyosarcoma originating from a bronchogenic cyst: A case report.

Mol Clin Oncol 2020 Mar 16;12(3):244-246. Epub 2020 Jan 16.

Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.

Mediastinal leiomyosarcoma is an aggressive tumor that primarily occurs in the posterior mediastinum. A bronchogenic cyst is a benign lesion that often develops in the mediastinum close to the thoracic trachea and has been reported to be the origin of certain malignancies. The present study reports an extremely rare case of an anterior mediastinal leiomyosarcoma that was considered to have originated from a bronchogenic cyst. An 82-year-old woman complained of chest pain, presenting an abnormal 70 mm mass shadow in the anterior mediastinum of a chest CT scan. Mediastinal tumor resection was performed and the tumor was diagnosed as a leiomyosarcoma. As the tumor was located adjacent to a bronchogenic cyst, it was considered to have originated from the remnant tissue of the cyst. Recurrent lesions were noted in the right lower lobe on CT scan 24 months after surgery.
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http://dx.doi.org/10.3892/mco.2020.1977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016609PMC
March 2020

ARL4C is associated with initiation and progression of lung adenocarcinoma and represents a therapeutic target.

Cancer Sci 2020 Mar 22;111(3):951-961. Epub 2020 Feb 22.

Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.

Lung adenocarcinoma is the most common histological type of lung cancer and is classified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). Atypical adenomatous hyperplasia (AAH) lesions are possible precursors to adenocarcinoma. However, the mechanism underlying the stepwise continuum of lung adenocarcinoma is unclear. In this study, the involvement of ADP-ribosylation factor (ARF)-like (ARL) 4C (ARL4C), a member of the small GTP-binding protein family, in the progression of lung adenocarcinoma and the possibility of ARL4C as a molecular target for lung cancer therapy were explored. ARL4C was frequently expressed in AAH and ARL4C expression in immortalized human small airway epithelial cells promoted cell proliferation and suppressed cell death. In addition, ARL4C was expressed with increased frequency in AIS, MIA and IA in a stage-dependent manner, and the expression was correlated with histologic grade, fluorine-18 fluorodeoxyglucose uptake and poor prognosis. An anti-sense oligonucleotide (ASO) against ARL4C (ARL4C ASO-1316) inhibited RAS-related C3 botulinum toxin substrate activity and nuclear import of Yes-associated protein and transcriptional coactivator with PDZ-binding motif, and suppressed in vitro proliferation and migration of lung cancer cells with KRAS or epidermal growth factor receptor (EGFR) mutations. In addition, transbronchial administration of ARL4C ASO-1316 suppressed orthotopic tumor formation induced by these cancer cells. Thus, ARL4C is involved in the initiation of the premalignant stage and is associated with the stepwise continuum of lung adenocarcinoma. ARL4C ASO-1316 would be useful for lung adenocarcinoma patients expressing ARL4C regardless of the KRAS or EGFR mutation.
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http://dx.doi.org/10.1111/cas.14303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060486PMC
March 2020

[Mediastinal Shift Due to the Rapidly Expanded Giant Bulla Probably Caused by the Lung Cancer].

Kyobu Geka 2019 Dec;72(13):1068-1071

Department of Thoracic Surgery, Kobe University, Kobe, Japan.

A 39-year-old man was admitted to our hospital with back pain and numbness of the left leg. Computed tomography (CT) showed a giant bulla and tumor in the right lung, mediastinal shift to the left side and lesions suggestive of metastatic sacral tumor. Three days later, the patient visited the emergency room with dyspnea and tachycardia. Chest CT showed the progression of mediastinal shift due to the rapid expansion of the giant bulla, and an emergency surgery was performed. After induction of anesthesia, sudden respiratory and circulatory failure occurred. Considering further expansion of the giant bulla by positive pressure ventilation, veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) was applied. After establishing ECMO, the condition of the patient became stable and the giant bulla could be resected successfully.
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December 2019

Complete resection of local advanced thymic carcinoma with total aortic arch replacement after chemotherapy: a case report.

Surg Case Rep 2019 Dec 12;5(1):198. Epub 2019 Dec 12.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, L5-2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.

Background: Although complete surgical resection of thymic carcinoma is a prognostic factor, it is not always an option for advanced tumors because of locoregional invasion. Extended surgery combined with a major blood vessel procedure remains controversial because of the increased risk of mortality.

Case Presentation: Chest computed tomography (CT) uncovered an abnormal shadow in the mediastinum of a 74-year-old man. An irregularly shaped tumor obstructed the left innominate vein, and invasion of the aortic arch was suspected. A CT-guided percutaneous needle biopsy revealed squamous cell carcinoma of the thymus, which was considered unresectable. The patient underwent chemotherapy elsewhere, then was referred to us for surgical resection. We combined extended surgery with total aortic arch replacement under a cardiopulmonary bypass. Complete resection was achieved, and the patient remains alive without recurrence at 3 years after surgery CONCLUSION: Resection including aortic arch replacement might be an option that can achieve complete resection of local advanced thymic carcinoma.
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http://dx.doi.org/10.1186/s40792-019-0713-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908541PMC
December 2019

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.

J Gastroenterol 2020 Mar 22;55(3):342-352. Epub 2019 Nov 22.

Department of Development Promotion, Clinical Research, Innovation, Education Center, Tohoku University Hospital, 1-1, Seiryo, Aoba-ku, Sendai, Miyagi, 9808574, Japan.

Background: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.

Methods: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.

Results: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.

Conclusions: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.
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http://dx.doi.org/10.1007/s00535-019-01644-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026212PMC
March 2020

Total thymectomy for thymic lymphoepithelioma-like carcinoma-report of two cases.

Surg Case Rep 2019 Oct 26;5(1):158. Epub 2019 Oct 26.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2(L5), Yamadaoka, Suita-shi, Osaka, 565-0871, Japan.

Background: Thymic carcinoma has been classified into 12 subtypes, thymic lymphoepithelioma-like carcinoma (LELC) is a type of them, and has a pathological organization similar to that of lymphoepithelioma, an undifferentiated type of nasopharyngeal carcinoma. According to a report from the International Thymic Malignancy Interest Group (ITMIG), thymic LELC is a rare tumor and accounts for 6% of all thymic carcinoma cases. We report two cases of surgical resection for thymic LELC and perform a search of other reports of thymic LELC, and clinical manifestations and follow-up data thus obtained are summarized.

Case Presentation: Two patients underwent surgical resection for thymic LELC. In both, tumors were detected in the anterior mediastinum and a total thymectomy was performed. Each was diagnosed with thymic LELC and classified in accordance with the Masaoka staging system as modified stage II. In recent examinations, one patient was doing well after undergoing total resection, whereas early recurrence of distant lymph node metastasis was noted in the other at 5 months after the total resection procedure and died thereafter from a different disease.

Conclusion: We report two cases of surgical resection for thymic LELC. A successful total resection may positively affect prognosis: thus, long-term follow-up examinations must be performed.
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http://dx.doi.org/10.1186/s40792-019-0706-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815289PMC
October 2019

Psf3 as a possible biomarker of postoperative chemotherapy for patients with early pulmonary adenocarcinoma.

Thorac Cancer 2019 12 22;10(12):2300-2307. Epub 2019 Oct 22.

Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Partner of Sld five 3 (Psf3) is a member of the heterotetrameric complex that consists of SLD5, Psf1, Psf2, and Psf3. We have shown in previous studies that high Psf3 expression was a poor prognostic marker for pulmonary adenocarcinoma. Here, we statistically evaluated the relationship between clinicopathologic factors and Psf3 expression in stage I pulmonary adenocarcinoma.

Methods: A total of 583 patients who had undergone complete resection of stage I pulmonary adenocarcinoma from January 2002 to December 2009 were included in the study. Tissue microarrays were performed, and the resected tumors were divided into groups according to Psf3 expression.

Results: Of 583 patients, high expression of Psf3 was observed in 211 (36.2%) and low expression of Psf3 observed in 372 (63.8%) patients. Among stage I patients, the five-year survival rate was 76.7% in the Psf3 high expression group and 90.9% in the Psf3 low expression group (P < 0.0001). On multivariate analysis, Psf3 was found to be the independent prognostic factor. Among stage I patients in the Psf3 high expression group, a significantly greater five-year survival rate was observed in patients who received postoperative chemotherapy with tegafur-uracil than in those who underwent surgery alone (P < 0.0001). In contrast, among stage I patients in the Psf3 low expression group, no difference was found in the five-year survival, regardless of the presence or absence of tegafur-uracil (P = 0.873).

Conclusion: The Psf3 expression was an independent prognostic factor and could be a biomarker of adjuvant tegafur-uracil for stage I pulmonary adenocarcinoma.

Key Points: Significant findings of the study: The Psf3 expression could be a biomarker of adjuvant tegafur-uracil administration for stage I pulmonary adenocarcinoma.

What This Study Adds: Appropriate patients of adjuvant chemotherapy for stage I pulmonary adenocarcinoma using Psf3 expression could be selected.
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http://dx.doi.org/10.1111/1759-7714.13230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885426PMC
December 2019

ASO Author Reflections: The Role of Surgical Resection for Pleural Dissemination of Thymoma.

Ann Surg Oncol 2019 12 25;26(Suppl 3):747-748. Epub 2019 Sep 25.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

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http://dx.doi.org/10.1245/s10434-019-07861-3DOI Listing
December 2019

[Tumor-induced Hypophosphatemic Osteomalacia Caused by a Chest Wall Tumor].

Kyobu Geka 2019 Aug;72(8):570-573

Department of Thoracic Surgery, Kobe University, Kobe, Japan.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disease characterized by hypophosphatemia and skeletal undermineralization. Overproduction of fibroblast growth factor 23( FGF23) from the responsible tumor is reported to be a causative factor. Removing the tumor is the only effective treatment for TIO, but identifying the tumor is sometimes difficult. A 43-year-old man complained of heel pain 4 years earlier, and the pain gradually expanded to the whole body. As a blood test showed the elevation of the serum FGF23 level and hypophosphatemia, he was diagnosed with FGF23-related hypophosphatemia. Chest computed tomography (CT) showed a 10-mm nodule in the right chest wall. Venous sampling for FGF23 revealed considerable elevation of the FGF23 level in the right subclavian vein. Therefore, a chest wall tumor was suspected as the tumor responsible for TIO, and surgical resection was performed. After surgery, hypophosphatemia improved within several days, and the FGF23 level also normalized.
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August 2019

Adipose Tissue-Derived Stem Cells Have the Ability to Differentiate into Alveolar Epithelial Cells and Ameliorate Lung Injury Caused by Elastase-Induced Emphysema in Mice.

Stem Cells Int 2019 10;2019:5179172. Epub 2019 Jun 10.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Adipose tissue-derived stem cells (ADSCs) are useful for ameliorating lung injury in animal models. However, whether ADSCs differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.
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http://dx.doi.org/10.1155/2019/5179172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590553PMC
June 2019

Long-Term Outcomes After Surgical Resection for Pleural Dissemination of Thymoma.

Ann Surg Oncol 2019 Jul 28;26(7):2073-2080. Epub 2019 Mar 28.

Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Background: Cases of thymoma with pleural dissemination are occasionally encountered, and their management is difficult. Some reports have noted that surgical treatment for dissemination is effective, although the long-term results and clinical course details remain unclear. The current study investigated the short- and long-term outcomes of surgical resection of pleural dissemination.

Methods: A retrospective review examined the medical records for 38 patients who underwent surgical resection for pleural dissemination occurring synchronously with a primary thymoma or metachronously after complete surgical resection of a primary thymoma between 1996 and 2017 at the authors' institution. Clinical characteristics and prognostic factors were analyzed.

Results: The patients were classified into synchronous (n = 21) and metachronous (n = 17) groups. The 10-year overall survival rate was 59% for the synchronous group and 88% for the metachronous group. The median follow-up period for all the patients was 61 months (range 4-225 months). No perioperative deaths occurred. For all the patients, the 5- and 10-year overall survival rates were respectively 91% and 82%, and the 5- and 10-year relapse-free survival rates were respectively 29% and 19%. A significantly worse prognosis was observed for patients 50 years of age or older than for those younger than 50 years (p = 0.02). For 13 patients who underwent repeat resection for pleural dissemination, the prognosis was better than for those without repeat resection (p < 0.01).

Conclusion: Surgical resection of thymoma with pleural disseminated nodules can be safely performed and provides a favorable long-term outcome. Repeat resection is considered to be effective for achieving a good prognosis.
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http://dx.doi.org/10.1245/s10434-019-07330-xDOI Listing
July 2019

Low incidence of thromboembolism in multiple myeloma patients receiving immunomodulatory drugs; a retrospective single-institution analysis.

J Thromb Thrombolysis 2019 Jul;48(1):141-148

Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30-85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21-2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings.
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http://dx.doi.org/10.1007/s11239-019-01809-wDOI Listing
July 2019

[MALT lymphoma accompanied by elevated serum IgM levels mimicking Waldenström's macroglobulinemia].

Rinsho Ketsueki 2018;59(12):2600-2605

Department of Hematology, Chiba University Hospital.

A 60-year-old man with chronic hepatitis C was referred to our hospital with significantly elevated total protein and serum IgM (9,500 mg/dl) levels identified via a routine checkup. Blood examination revealed increased serum IgM-monoclonal protein and serum-soluble IL-2 receptor (sIL2R) levels. Computed tomography and fluorodeoxyglucose positron emission tomography revealed pulmonary masses, abnormal soft tissue masses surrounding the bilateral kidneys, and thickened mucous membrane of the bladder with high fluorodeoxyglucose uptake. Pathological examination of the pulmonary mass revealed infiltration of medium-sized lymphocytes and plasma cells. Immunohistochemical analysis revealed tumor cells positive for CD138 and IgM, with a low positive rate of Ki-67 expression. Notably, the tumor cell-surrounding lymphocytes were positive for CD20. Although the patient was initially regarded as having Waldenström's macroglobulinemia owing to the significantly increased serum IgM levels, based on positive IgH-MALT1 translocation and negative MYD88 L265P mutation findings, he was further diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Complete remission was achieved following six cycles of rituximab + CHOP therapy. This study data suggest that analysis of the MYD88 L265P mutation in tumor cells is suitable for accurately diagnosing hematopoietic malignancies with increased IgM monoclonal protein.
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http://dx.doi.org/10.11406/rinketsu.59.2600DOI Listing
July 2019

[Temporary Bypass with 5-Fr Catheter for Reconstruction of Superior Vena Cava].

Kyobu Geka 2018 12;71(13):1077-1080

Division of Thoracic Surgery, Kobe University, Kobe, Japan.

A 21-year-old man was referred to our hospital because of an abnormal shadow on a routine chest radiogram. Enhanced computed tomography showed an 83×74 mm mass in the anterior mediastinum, with invasion of the superior vena cava (SVC). Surgical resection with sternotomy was performed. Intraoperative temporary bypass grafting with a 5-Fr catheter was performed between the right brachiocephalic vein and right atrium. The mediastinal tumor was resected with the SVC, and SVC reconstruction with a 16 mm expanded polytetrafluoroethylene graft was performed. The bypass stabilized intraoperative vital signs and enabled safe completion of the operation. The pathological diagnosis was seminoma. SVC replacement combined with temporary bypass using a small diameter catheter is technically feasible and safe.
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December 2018

Combined Aortic Arch Resection for Lung Cancer Using Total Rerouting of Supra-Arch Vessels.

Ann Thorac Surg 2019 Jun 1;107(6):e399-e401. Epub 2018 Dec 1.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Surgery for aortic arch involvement in lung cancer cases is challenging, and generally requires extracorporeal circulation with circulatory arrest or a cerebral protection technique. To reduce morbidity, we developed a novel surgical technique for total aortic arch replacement for lung cancer with aortic arch involvement that features total rerouting of supra-arch vessels under a beating heart condition. A 56-year-old man was diagnosed with lung cancer, and aortic arch invasion was suspected. After concurrent chemoradiotherapy, a left upper lobectomy with total arch replacement was performed using our new technique. Thirty-six months after the operation, there was no recurrence.
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http://dx.doi.org/10.1016/j.athoracsur.2018.10.059DOI Listing
June 2019

[A case of non-invasive IPMC with fibrotic lesion-like "tubular complex"].

Nihon Shokakibyo Gakkai Zasshi 2017;114(12):2142-2150

Department of Gastroenterology, National Hospital Organization Sendai Medical Center.

A 73-year-old man was incidentally diagnosed with a cystic lesion in the pancreatic body. Ultrasonography, abdominal computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound were performed, and a nodule was detected in the cystic lesion along with an irregularity of the main pancreatic duct. An initial diagnosis of a mixed-type intraductal papillary mucinous neoplasm was made, and a central pancreatectomy was performed. However, the final diagnosis was altered to non-invasive intraductal papillary mucinous carcinoma (IPMC). The histopathological examination revealed a fibrotic lesion that was similar to "tubular complex" findings observed in mouse models of pancreatic cancer. The fibrotic lesion was placed between the main pancreatic duct lesion and branch-duct cystic lesion. The changes reflected in branch-level stenosis may be caused by IPMC growth.
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http://dx.doi.org/10.11405/nisshoshi.114.2142DOI Listing
June 2018