Publications by authors named "Jun Nakajima"

358 Publications

Genetic diversification of the Kanehira bitterling Acheilognathus rhombeus inferred from mitochondrial DNA, with comments on the phylogenetic relationship with its sister species Acheilognathus barbatulus.

J Fish Biol 2021 Sep 9. Epub 2021 Sep 9.

Faculty of Bioresources, Mie University, Tsu, Japan.

The Kanehira bitterling, Acheilognathus rhombeus, is a freshwater fish, discontinuously distributed in western Japan and the Korean Peninsula. Unusually among bitterling it is an autumn-spawning species and shows developmental diapause. Consequently, the characterization of its evolutionary history is significant not only in the context of the fish assemblage of East Asia, but also for understanding life-history evolution. This study aimed to investigate the phylogeography of A. rhombeus and its sister species Acheilognathus barbatulus, distributed in China, using a mitochondrial analysis of the ND1 gene from 311 samples collected from 50 localities in Japan and continental Asia. Phylogenetic analysis revealed that A. barbatulus is included in A. rhombeus and genetically closer to Japanese A. rhombeus than to Korean A. rhombeus. Divergence of Korean A. rhombeus and A. barbatulus from Japanese A. rhombeus was estimated to be from the late Pliocene (3.44 Mya) and the early Pleistocene (1.98 Mya), respectively. Each event closely coincided with the time of the Japan Sea opening. Japanese A. rhombeus comprised seven lineages: three in Honshu and four in Kyushu. One lineage in central Kyushu was genetically closer to the Honshu lineages than to other lineages in northern Kyushu. Divergence of Japanese lineages was estimated to be from the early to middle Pleistocene (0.55-0.93 Mya), during a period of geological and paleoclimatic change, including volcanic activity. Population expansion in the late Pleistocene (<0.10 Ma) was suggested in many of the lineages, which accords with other freshwater fishes. Biogeographically the ancestral A. rhombeus/A. barbatulus was likely to have repeatedly colonized Japan from the continent through land bridges in the late Pliocene and the early Pleistocene. However, the close genetic relationship between Japanese A. rhombeus and A. barbatulus suggests another possibility, with the second colonization occurring in reverse, from Japan to China. The small genetic distance between them indicates that the colonization occurred later than colonization events of other freshwater fishes, including other bitterling species.
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http://dx.doi.org/10.1111/jfb.14876DOI Listing
September 2021

Lung transplant after long-term veno-venous extracorporeal membrane oxygenation: a case report.

J Cardiothorac Surg 2021 Aug 30;16(1):246. Epub 2021 Aug 30.

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

Background: Although the number of patients who undergo extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is increasing worldwide, there are few reports on lung transplantation after long-term ECMO (more than 1 month). We report a rare case of successful bilateral lung transplantation in a Japanese patient after 5 months of veno-venous (VV)-ECMO support.

Case Presentation: A 27-year-old man who underwent bone marrow transplantation (BMTx) with fully matched human leukocyte antigen typing was diagnosed with bronchiolitis obliterans caused by chronic graft-versus-host disease 3 years after the BMTx. One year later, his respiratory condition had exacerbated, with carbon dioxide retention that required conventional mechanical ventilation. He was then deemed a suitable candidate for lung transplantation by a multidisciplinary transplantation selection committee. While waiting for donor lungs, his hypercapnia and acidosis became barely manageable under care with mechanical ventilation and ultimately he was switched to VV-ECMO. He remained on VV-ECMO for the next 5 months, during which period the circuit was switched nine times. In addition, sophisticated intensive care was required to manage multiple episodes of sepsis and coagulopathy. A suitable donor was identified 5 months later, and bilateral lung transplantation was initiated with continuous VV-ECMO. The procedure itself was extremely challenging owing to severe adhesions resulting from previous thoracotomy, inflammation, infection, and intrapulmonary hemorrhage. The operative time for the transplantation was about 19 h. Currently, at 2 years 8 months postoperatively, the patient is alive and well.

Conclusion: Transplant surgery in this patient was extremely challenging because of the presence of severe pleural adhesions and stiff native lungs secondary to hemorrhagic complications due to the prolonged ECMO support. Surgeons must recognize that lung transplantation after long-term ECMO bridging can be technically more complicated and challenging than shorter-term ECMO.
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http://dx.doi.org/10.1186/s13019-021-01614-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404359PMC
August 2021

Influence of the prehospital administered dosage of epinephrine on the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest.

Heliyon 2021 Aug 5;7(8):e07708. Epub 2021 Aug 5.

Department of Emergency Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

Aim: This study evaluated whether the prehospital administered dosage of epinephrine (Ep) influences the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest (OHCA).

Methods: This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were analyzed. The plasma levels of catecholamines were measured using blood samples obtained immediately upon arrival at the hospital and before the administration of Ep. Patients were divided into three groups based on the prehospital administered dosage of Ep: no prehospital administration (group Z); 1 mg of Ep (group O); and 2 mg of Ep (group T). The levels of catecholamines, as well as the conditions of resuscitation prior to and after arrival at the hospital were compared between the three groups.

Results: We analyzed 145 patients with OHCA (96, 38, and 11 patients in groups Z, O, and T, respectively). Group T exhibited the highest plasma levels of Ep with a statistically significant difference, however, there were no significant differences in the plasma levels of norepinephrine (Nep), dopamine (DOA) and vasopressin (ADH) among the three groups.

Conclusion: The prehospital administered dosage of Ep influences the plasma levels of Ep; however, it does not contribute to the plasma levels of Nep, DOA and ADH in patients with OHCA.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353485PMC
August 2021

Relationship between the Plasma Levels of Catecholamines and Return of Spontaneous Circulation in Patients with Out-of-Hospital Cardiac Arrest.

Emerg Med Int 2021 29;2021:5324038. Epub 2021 Jul 29.

Department of Emergency Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.

Purpose: The dynamic state of epinephrine (Ep) in the plasma of patients with out-of-hospital cardiac arrest (OHCA) remains unclear. The purpose of this study was to evaluate the relationship between the plasma levels of catecholamines (such as epinephrine (Ep), norepinephrine (Nep), and dopamine) and vasopressin (antidiuretic hormone (ADH)) and the acquisition of return of spontaneous circulation (ROSC) in OHCA patients.

Methods: This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were enrolled. The levels of catecholamines and ADH in the plasma were measured using blood samples immediately obtained on arrival at our hospital and before the administration of Ep. Patients in whom Ep was already administered prior to obtaining blood samples were excluded. Patients were divided into two groups: with and without ROSC, that is, ROSC (+) and ROSC (-) groups, respectively. The plasma levels of these agents and the conditions of resuscitation were compared between the two groups.

Results: A total of 96 patients with OHCA were analyzed. The ROSC (+) and ROSC (-) groups included 34 and 62 patients, respectively. There were no significant differences observed between the two groups in age, cause of cardiopulmonary arrest, and prehospital resuscitation time. The plasma levels of Ep and Nep were significantly lower in the ROSC (+) group than in the ROSC (-) group. However, there were no significant differences in the plasma levels of dopamine and ADH between the two groups.

Conclusion: Increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with OHCA.
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http://dx.doi.org/10.1155/2021/5324038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342156PMC
July 2021

Lobectomy for lung cancer in a patient with Fontan circulation: A case report.

JTCVS Tech 2021 Apr 6;6:163-165. Epub 2021 Jan 6.

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

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http://dx.doi.org/10.1016/j.xjtc.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300905PMC
April 2021

SARS-CoV-2 R.1 lineage variants that prevailed in Tokyo in March 2021.

J Med Virol 2021 Jul 27. Epub 2021 Jul 27.

Clinical Laboratory, Tokyo Medical and Dental University (TMDU) Hospital, Tokyo, Japan.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as B.1.1.7 and B.1.351, has become a crucial issue worldwide. Therefore, we began testing all patients with COVID-19 for the N501Y and E484K mutations by using polymerase chain reaction (PCR)-based methods. Nasopharyngeal swab samples from 108 patients who visited our hospital between February and April 2021 were analyzed. The samples were analyzed using reverse transcription-PCR with melting curve analysis to detect the N501Y and E484K mutations. A part of the samples was also subjected to whole-genome sequencing (WGS). Clinical parameters such as mortality and admission to the intensive care unit were analyzed to examine the association between increased disease severity and the E484K mutation. The ratio of cases showing the 501N + 484K mutation rapidly increased from 8% in February to 46% in March. WGS revealed that the viruses with 501N + 484K mutation are R.1 lineage variants. Evidence of increased disease severity related to the R.1 variants was not found. We found that the R.1 lineage variants rapidly prevailed in Tokyo in March 2021, which suggests the increased transmissibility of R.1 variants, while they showed no increased severity.
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http://dx.doi.org/10.1002/jmv.27240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426954PMC
July 2021

Successful interventional management of mediastinal hematoma caused by thyroid ima artery injury.

Acute Med Surg 2021 Jan-Dec;8(1):e680. Epub 2021 Jul 2.

Department of Gunma University Graduate School of Medicine Maebashi Japan.

Background: The thyroid ima artery (ThIA) is a rare anatomical anomaly, commonly branching from the brachiocephalic artery. Thyroid ima artery injury can cause severe mediastinal hematoma because its descending branch extends into the mediastinum.

Case Presentation: A 91-year-old man presented with syncope after a motor vehicle accident. A bruise on the chest was evident. Contrast-enhanced computed tomography revealed a massive mediastinal hematoma with signs of active hemorrhage. Injury to a descending branch of the ThIA was indicated. Transcatheter arterial embolization (TAE) was successful in stopping the bleeding.

Conclusions: Although a ThIA injury is rare, it can cause serious mediastinal hematoma. Thyroid ima artery injury should be considered as a cause of traumatic mediastinal hematoma. Transcatheter arterial embolization for traumatic ThIA injury is considered a safe and effective treatment.
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http://dx.doi.org/10.1002/ams2.680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253541PMC
July 2021

Managing screening-detected subsolid nodules-the Asian perspective.

Transl Lung Cancer Res 2021 May;10(5):2323-2334

Department of Thoracic Surgery, National Taiwan University Hospital, Taipei.

The broad application of low-dose computed tomography (CT) screening has resulted in the detection of many small pulmonary nodules. In Asia, a large number of these detected nodules with a radiological ground glass pattern are reported as lung adenocarcinomas or premalignant lesions, especially among female non-smokers. In this review article, we discuss controversial issues and conditions involving these subsolid pulmonary nodules that we often face in Asia, including a lack or insufficiency of current guidelines; the roles of preoperative biopsy and imaging; the location of lesions; appropriate selection of localization techniques; the roles of dissection and sampling of frozen sections and lymph nodes; multifocal lesions; and the roles of non-surgical treatment modalities. For these complex issues, we have tried to present up-to-date evidence and our own opinions regarding the management of subsolid nodules. It is our hope that this article helps surgeons and physicians to manage the complex issues involving ground glass nodules (GGNs) in a balanced manner in their daily practice and provokes further discussion towards better guidelines and/or algorithms.
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http://dx.doi.org/10.21037/tlcr-20-243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182721PMC
May 2021

Comprehensive molecular profiling of pulmonary pleomorphic carcinoma.

NPJ Precis Oncol 2021 Jun 22;5(1):57. Epub 2021 Jun 22.

Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.

Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.
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http://dx.doi.org/10.1038/s41698-021-00201-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219709PMC
June 2021

Efficacy of the treatment for elderly emergency patients with sepsis.

Heliyon 2021 May 28;7(5):e07150. Epub 2021 May 28.

Department of Emergency Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

Objectives: We evaluated the impact of age in septic patients admitted through the ER on clinical outcome and cost.

Methods: Patients with sepsis admitted to the intensive care unit (ICU) through the emergency room in our hospital between January 2013 and December 2018 were analyzed. They were divided into three groups according to their age: <65 years (group Y); 65-79 years (group M); and ≥80 years (group E). The duration of ICU and hospital stay, prognosis, and total hospital costs were compared among the three groups.

Results: During this period, 1,392 patients were admitted to the ICU through the emergency room, and 174 patients with sepsis were analyzed. There were 49, 79, and 46 patients in groups Y, M, and E, respectively. There was no significant difference in ICU stay. Group E exhibited the shortest hospital stay and the lowest total hospital cost with statistically significant difference (p = 0.010 and p = 0.007, respectively). However, group E showed the highest rate of hospital mortality (30.4%) compared to groups Y and M (14.3% and 21.5%, respectively; p = 0.163).

Conclusions: Elderly (aged ≥80 years) emergency patients with sepsis require shorter hospital stay and are associated with lower total hospital cost. However, it may be difficult for these patients to maintain the hospital mortality equivalent to those observed in patients aged <80 years.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180618PMC
May 2021

Current status of inhaled nitric oxide therapy for lung transplantation in Japan: a nationwide survey.

Gen Thorac Cardiovasc Surg 2021 Oct 17;69(10):1421-1431. Epub 2021 May 17.

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

Objectives: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation.

Methods: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan.

Results: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years.

Conclusions: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.
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http://dx.doi.org/10.1007/s11748-021-01648-8DOI Listing
October 2021

Proton conductivity in mixed cation phosphate, KMgH(PO)·HO, with a layered structure at low-intermediate temperatures.

Dalton Trans 2021 Jun;50(22):7678-7685

Department of Applied Chemistry, Faculty of Engineering, Osaka Institute of Technology, 5-16-1 Ohmiya, Asahi-Ku, Osaka, 535-8585, Japan.

Proton solid electrolytes, which exhibit high proton conductivity at a wide range of low-intermediate temperatures (150-300 °C), are key materials for the development of fuel cells for automobiles and cogeneration systems. In this study, a benitoite-type polyphosphate, KMg1-xH2x(PO3)·yH2O, which has a non-combustible and layered structure, was investigated as a new proton conductor. The benitoite-type KMg1-xH2x(PO3)·yH2O was synthesised by a coprecipitation method. The solid solution formed in the range of x = 0-0.100 in KMg1-xH2x(PO3)3·yH2O. Multi-step weight loss due to dehydration was observed for TG/DTA measurement at 30 °C and 150 °C. We observed enhanced peaks of the vibration bands at around 1117 cm-1 and 1229 cm-1, which were attributed to the symmetric and asymmetric PO2 vibration modes, and at 743 cm-1 and 970 cm-1 due to the ns(P-O-P) and nas(P-O-P) modes as well as broad absorbance peaks at 2300 cm-1 and 2700 cm-1 corresponding to the vibration modes of ns(P-O-H) with increasing x for FTIR spectra, which suggest the introduction of protons to the crystal structure. Proton conductivity increased from x = 0 to 0.10 and then decreased at x = 0.125, where the impurity phase was observed. The sample with x = 0.10 in benitoite-type KMg1-xH2x(PO3)3·yH2O exhibited high proton conductivity of 1.4 × 10-3 S cm-1 at 150 °C and 6.5 × 10-3 S cm-1 at 250 °C under a non-humidified N2 gas flow.
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http://dx.doi.org/10.1039/d1dt01187aDOI Listing
June 2021

Intrabronchial migration of hemostatic agent through a bronchial fistula after lung transplantation: a case report.

Surg Case Rep 2021 May 10;7(1):116. Epub 2021 May 10.

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

Background: A bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula.

Case Presentation: A 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery.

Conclusion: We experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.
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http://dx.doi.org/10.1186/s40792-021-01200-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110655PMC
May 2021

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Real-World Safety Profile of Atrial Fibrillation Ablation Using a Second-Generation Cryoballoon in Japan: Insight From a Large Multicenter Observational Study.

JACC Clin Electrophysiol 2021 05 24;7(5):604-613. Epub 2021 Feb 24.

Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

Objectives: This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan.

Background: Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy.

Methods: This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected.

Results: Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia.

Conclusions: This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.
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http://dx.doi.org/10.1016/j.jacep.2020.11.016DOI Listing
May 2021

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

Surg Today 2021 Aug 12;51(8):1276-1284. Epub 2021 Feb 12.

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

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

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

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

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

Resection of clustered arteriovenous malformations to avoid lung transplantation.

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

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

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

Management of Partial Anomalous Pulmonary Venous Return In Lung Transplantation.

Ann Thorac Surg 2021 08 10;112(2):e95-e97. Epub 2021 Jan 10.

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

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

Tumor Growth Suppression With Novel Intra-arterial Chemotherapy Using Epirubicin-entrapped Water-in-oil-in-water Emulsion .

In Vivo 2021 Jan-Feb;35(1):239-248

Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, Japan.

Background/aim: A mixture of anticancer agents and iodized poppy seed oil (IPSO) has been widely used for intra-arterial chemotherapy of hepatocellular carcinoma. However, the anticancer agents can easily separate from IPSO, so the therapeutic potential is limited. We developed epirubicin-entrapped water-in-oil-in-water emulsion (WOW-Epi) using a double-membrane emulsification technique.

Materials And Methods: We delivered WOW-Epi through a hepatic arterial injection to VX2 hepatic tumor rabbit model (1.2 mg/kg).

Results: VX2 tumor growth was selectively suppressed in the WOW-Epi-treated group compared with the control treated groups. The accumulation of WOW in nearby cancer cells was confirmed via electron-microscopy. Endocytosis seemed to be the mechanism underlying the uptake of WOW.

Conclusion: WOW-Epi led to tumour growth suppression in vivo. WOW does not cause toxicity to arterial vessels. WOW-Epi will be hopefully used for repeated intra-arterial chemotherapy to HCC patients in the near future.
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http://dx.doi.org/10.21873/invivo.12252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880746PMC
June 2021

National survey of bladder endometriosis cases in Japan.

J Obstet Gynaecol Res 2021 Apr 4;47(4):1451-1461. Epub 2021 Jan 4.

Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.

Aim: We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE).

Methods: We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence.

Results: Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p < 0.05). The recurrence rate tended to be higher after laparoscopic PC (n = 24) than after open PC (n = 20), but the difference was not statistically significant (p = 0.0879). Of the nine nonsurgical patients, eight received hormonal therapy and one did not. Efficacy rates of dienogest, GnRH agonist, and OC were 85.7%, 66.7%, and 66.7%, respectively. Of five patients with BE extending to the ureter or ureteral orifices, two underwent PC and ureteroneocystostomy and one underwent total nephroureterectomy due to renal function loss.

Conclusion: To our knowledge, this is the first study to compare the postoperative recurrence of BE after TUR and PC. We found that cumulative recurrence rate is significantly lower after PC than after TUR. BE extending to the ureter or ureteral orifices is a very challenging condition. Further studies are required for the optimal management of BE.
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http://dx.doi.org/10.1111/jog.14656DOI Listing
April 2021

Prospective study of recurrence at the surgical margin after wedge resection of pulmonary metastases.

Gen Thorac Cardiovasc Surg 2021 Jun 3;69(6):950-959. Epub 2021 Jan 3.

Department of Thoracic Surgery, National Defense Medical College, Saitama, Japan.

Background: Pulmonary metastasectomy is a common treatment for selected patients with pulmonary metastases. Among pulmonary resections, wedge resection is considered sufficient for pulmonary metastases. However, a major problem with wedge resection is the risk of local recurrence, especially at the surgical margin. The aim of this prospective study was to explore the frequency of and the risk factors for recurrence at the surgical margin in patients who underwent wedge resection for pulmonary metastases.

Methods: Between September 2013 and March 2018, 177 patients (220 lesions) with pulmonary metastases from 15 institutions were enrolled. We studied 130 cases (169 lesions) to determine the frequency of and risk factors associated with recurrence at the surgical margin in patients who underwent wedge resection. Moreover, we evaluated the recurrence-free rate and disease-free survival after wedge resection.

Results: A total of 81 (62.3%) patients developed recurrence. Recurrence at the surgical margin was observed in 11 of 130 (8.5%) cases. The 5-year recurrence-free rate was 89.1%. Per patient, multivariable analysis revealed that the presence of multiple pulmonary metastases was a significant risk factor for recurrence. Per tumor, distance from the surgical margin and tumor/margin ratio were risk factors for local recurrence. The 5-year disease-free survival rate was 34.7%, and the presence of multiple pulmonary metastases and small surgical margin were risk factors for disease-free survival by univariable analysis.

Conclusions: Among patients who undergo wedge resection for pulmonary metastasis, patients with multiple pulmonary metastases tend to develop recurrence at the surgical margin.
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http://dx.doi.org/10.1007/s11748-020-01560-7DOI Listing
June 2021

Simultaneous single lobar lung transplantation and contralateral lung volume reduction.

Eur J Cardiothorac Surg 2021 06;59(6):1342-1344

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

Lung transplantation (LTx) and lung volume reduction surgery are established therapies for end-stage chronic obstructive pulmonary disease. Although native lung hyperinflation is a well-known complication of unilateral LTx for chronic obstructive pulmonary disease, the unilateral procedure continues to be performed because of severe shortages of cadaveric donors. As native lung hyperinflation can adversely affect the graft, all possible protection should be provided for patients with one-lobe transplantation. We report an emphysematous juvenile patient who successfully underwent simultaneous living-donor, single-lobe LTx and volume reduction in the contralateral lung.
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http://dx.doi.org/10.1093/ejcts/ezaa459DOI Listing
June 2021

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

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

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

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

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

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

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

Pulmonary metastasectomy for pulmonary metastasis of breast cancer has a limited prognostic impact: a multi-institutional retrospective analysis.

J Thorac Dis 2020 Nov;12(11):6552-6562

Division of General Thoracic Surgery, Teikyo University, School of Medicine, Tokyo, Japan.

Background: Pulmonary metastasectomy (PM) for breast cancer-derived pulmonary metastasis is controversial. This study aimed to assess the prognostic factors and implication of PM for metastatic breast cancer using a multi-institutional database.

Methods: Clinical data of 253 females with pulmonary metastasis of breast cancer who underwent PM between 1982 and 2017 were analyzed retrospectively.

Results: The median patient age was 56 years. The median follow-up period was 5.4 years, and the median disease-free interval (DFI) was 4.8 years. The 5- and 10-year survival rates after PM were 64.9% and 50.4%, respectively, and the median overall survival was 10.1 years. Univariate analysis revealed that the period of PM before 2000, a DFI <36 months, lobectomy/pneumonectomy, large tumor size, and lymph node metastasis were predictive of a worse overall survival. In the multivariate analysis, a DFI <36 months, large tumor size, and lymph node metastasis remained significantly related to overall survival. The 5- and 10-year cancer-specific survival rates after PM were 66.9% and 54.7%, respectively, and the median cancer-specific survival was 13.1 years. Univariate analyses revealed that the period of PM before 2000, DFI <36 months, lobectomy/pneumonectomy, large tumor size, lymph node metastasis, and incomplete resection were predictive of a worse cancer-specific survival. Multivariate analysis confirmed that a DFI <36 months, large tumor size and incomplete resection were significantly related to cancer-specific survival.

Conclusions: As PM has limited efficacy in breast cancer, it should be considered an optional treatment for pulmonary metastasis of breast cancer.
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http://dx.doi.org/10.21037/jtd-20-1788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711388PMC
November 2020

Reply to "Euclidean Geometry Versus Metabolic Biochemistry in the Prognostic Evaluation of the Thymic Epithelial Tumours".

Ann Surg Oncol 2021 07 13;28(7):4060-4061. Epub 2020 Nov 13.

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

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http://dx.doi.org/10.1245/s10434-020-09349-xDOI Listing
July 2021

Reversible brain imaging findings with a severe neurological prognosis of neuroleptic malignant syndrome.

Heliyon 2020 Oct 30;6(10):e05374. Epub 2020 Oct 30.

Department of Emergency Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Neuroleptic malignant syndrome is a rare but life-threatening disorder associated with the use of neuroleptic drugs, and is characterized by fever, altered mental status, muscle rigidity, autonomic instability, myoclonus, elevated creatine kinase levels, rhabdomyolysis, and leukocytosis. Previous reports have shown that most patients with neuroleptic malignant syndrome recover without neurologic sequelae. Some patients with neuroleptic malignant syndrome show reversible magnetic resonance imaging (changes in the brain. The severe neurological impairments do not persist in neuroleptic malignant syndrome patients with reversible lesions. Here, we describe a 66-year-old Japanese woman who was diagnosed with septic shock secondary to obstructive pyelonephritis. She was administered haloperidol for delirium and developed neuroleptic malignant syndrome. Magnetic resonance imaging of the brain showed diffuse hyperintense signals in the cerebellar cortex, cerebellar dentate nucleus, superior cerebellar peduncle, and thalamus on T2-weighted imaging or fluid-attenuated inversion recovery, and in the bilateral substantia nigra and bilateral globus pallidus on diffusion-weighted imaging. Subsequently, the signal intensities of the cerebellar and thalamic lesions diminished and the basal ganglia lesions disappeared, but the severe neurologic sequelae remained. The cerebellum is reportedly particularly sensitive to thermal damage because Purkinje cells are believed to be vulnerable to heat. Although brain imaging studies revealed reversible changes, her disturbance of consciousness was prolonged. Therefore, brain magnetic resonance imaging findings might not reflect the neurologic prognosis in patients with neuroleptic malignant syndrome.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610276PMC
October 2020

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

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

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

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

Impact of Surgical Resection on Metachronous Metastases of Colorectal Cancer According to Tumor Doubling Time.

In Vivo 2020 Nov-Dec;34(6):3367-3374

Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.

Background/aim: We aimed to elucidate the prognostic impact of tumor doubling time (DT) and radical surgery when classified by DT in patients with metachronous liver, lung, or peritoneal metastases of colorectal cancer (CRC).

Patients And Methods: We reviewed the data of 1941 patients who underwent curative surgery for CRC and calculated DT for recurrences using computed tomography.

Results: Short DT was an independent prognostic risk factor in liver (p<0.001) and peritoneal (p=0.03) metastases. Survival was significantly better in patients who underwent surgery than in those who did not, both in short and long DT groups in any metastatic organ (p<0.01). Patients with long DT gained significantly better prognostic benefit from surgery than those with short DT in liver (p=0.01) and peritoneal (p=0.04) metastases.

Conclusion: Surgery is recommended for resectable metastases, especially in patients with liver and peritoneal metastases with long DT.
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http://dx.doi.org/10.21873/invivo.12175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811596PMC
June 2021
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