Publications by authors named "Masaki Anraku"

92 Publications

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

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

Artificial lungs--Where are we going with the lung replacement therapy?

Artif Organs 2020 Nov 23;44(11):1135-1149. Epub 2020 Oct 23.

Cardio-Thoracic Surgery Department - Heart & Vascular Centre, Maastricht University Medical Hospital, Maastricht, The Netherlands.

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy.
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http://dx.doi.org/10.1111/aor.13801DOI Listing
November 2020

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

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

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

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

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

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

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

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

Oncol Lett 2020 Apr 17;19(4):2695-2704. Epub 2020 Feb 17.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.
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http://dx.doi.org/10.3892/ol.2020.11407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068670PMC
April 2020

International Delphi survey of the ESTS/AATS/ISTH task force on venous thromboembolism prophylaxis in thoracic surgery: the role of extended post-discharge prophylaxis.

Eur J Cardiothorac Surg 2020 05;57(5):854-859

Department of Surgery, McMaster University, Hamilton, ON, Canada.

Objectives: Venous thromboembolic events can be successfully prevented with chemical and/or mechanical prophylaxis measures, but evidence-based guidelines in thoracic surgery are limited, particularly regarding extended post-discharge prophylaxis. This study attempts to gather an international consensus on best practices to inform the development of such guidelines.

Methods: A series of 3 surveys was distributed to the ESTS/AATS/ISTH (European Society of Thoracic Surgeons, American Association of Thoracic Surgeons, International Society for Thrombosis and Haemostasis) venous thromboembolic events prophylaxis working group starting January 2017. This iterative Delphi consensus process sought to gather a consensus on (i) risk factors; (ii) preferred agents; (iii) duration; and (iv) perceived barriers to an extended thromboprophylaxis approach. Participant responses were expressed on a 10-point scale, and the results were summarized and circulated to all respondents in subsequent rounds. A coefficient of variance of ≤0.3 was identified pre hoc to identify agreement.

Results: A total of 21 Working Group members completed the surveys, composed of 19% non-surgeon thrombosis experts, and 48% from North America. Respondents largely saw agreement regarding risk factors that indicate a need for extended thromboprophylaxis. The group agreed that low-molecular-weight heparin is a suitable agent for use post-discharge, but there was a wide variety in response regarding agents, duration and barriers to extended prophylaxis, where no consensus was observed across the three rounds.

Conclusions: There is strong agreement around indications for extended venous thromboembolic events thromboprophylaxis after thoracic surgery, but there is little consensus regarding the agents and duration to be employed. Further research is required to better inform guideline development.
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http://dx.doi.org/10.1093/ejcts/ezz319DOI Listing
May 2020

[Reexpansion Pulmonary Edema and Atrial Fibrillation after Resection of a Giant Solitary Fibrous Tumor of the Pleura].

Kyobu Geka 2019 Nov;72(12):997-1000

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

We report a case of giant solitary fibrous tumor( SFT) of the pleura postoperatively complicated with probable reexpansion pulmonary edema and atrial fibrillation. An 85-year-old woman was diagnosed to have a 13 cm sized intrathoracic neoplasm. Upon thoracotomy, the tumor was found to pedunculate from the right lung with no direct invasion to the surrounding structures. Complete resection of the tumor and expansion of the right lung was obtained. Histopathology revealed the tumor was a benign SFT arising from the visceral pleura. An infiltrative shadow in the right lower lung field soon after the surgery suggested a reexpansion pulmonary edema, which eventually recovered within a week. The patient suffered from a refractory atrial fibrillation that led to a congestive heart failure requiring an intensive medical treatment. It is emphasized that thoracic surgeons should be aware of these postoperative complications in treating such a case like this.
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November 2019

Tumor location may affect the clinicopathological features and prognosis of thymomas.

Thorac Cancer 2019 11 9;10(11):2096-2105. Epub 2019 Sep 9.

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

Background: The current staging systems do not consider the tumor location of thymomas, and its clinical relevance is poorly understood. This study aimed to evaluate the impact of tumor location on the clinicopathological features and prognosis of thymomas.

Methods: We performed a retrospective review of patients at our institution who underwent an extended thymectomy for a thymoma from 1976 to 2015. The tumor location was classified as either the superior or inferior mediastinum based on the maximum tumor diameter. The clinicopathological characteristics of the thymoma were also evaluated. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze the survival outcomes and risk factors for recurrence.

Results: A total of 194 patients with thymoma were eligible for this study. Compared with the inferior mediastinum group (n = 167), the superior mediastinum group (n = 27) had a higher frequency of myasthenia gravis (MG), advanced Masaoka-Koga staging, disease progression and recurrence (P < 0.05). The Kaplan-Meier analysis demonstrated thymomas in the superior mediastinum had worse survival outcomes that included overall survival, progression-free survival and disease-free survival (P < 0.05). The multivariate analysis showed tumor location was an independent prognostic factor for all the survival outcomes (P < 0.05). Furthermore, the tumor location (P = 0.004) and Masaoka-Koga stage (P < 0.001) were the only two independent risk factors for recurrence in the multivariate analysis.

Conclusions: The clinicopathological features of thymomas on MG, Masaoka-Koga staging, disease progression, and recurrence were different between locations of superior and inferior mediastinum locations. Thymomas in the superior mediastinum tended to be associated with worse survival and increased recurrence.
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http://dx.doi.org/10.1111/1759-7714.13188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825910PMC
November 2019

Impact of Previous Malignancy on Outcome in Surgically Resected Non-Small Cell Lung Cancer.

Ann Thorac Surg 2019 12 14;108(6):1671-1677. Epub 2019 Aug 14.

The University of Tokyo, Tokyo, Japan.

Background: Patients with lung cancer with a history of treatment often undergo curative surgical resection. However, the impact of previous cancer treatment on the outcome of lung cancer remains unclear.

Methods: We conducted a retrospective study of patients who underwent curative resection for non-small cell lung cancer between 1998 and 2011. We collected clinicopathologic data and patients were divided into groups by previous history of cancer treatment. Comparisons between groups, estimation of survival rates, and multivariate analyses were performed. Propensity score matching was used to create cohorts with reduced bias.

Results: Of 878 patients, 196 (22.3%) had previous extrathoracic malignancies, and stage I lung cancer was more frequent in this group (P < .001). In multivariate analysis of the whole cohort, older patients, men, non-adenocarcinoma histologic type, more advanced pathologic stage of lung cancer, interstitial pneumonia, and previous extrathoracic malignancies were associated with appreciably worse prognosis. When propensity score matched cohorts were compared, prognosis was significantly worse in patients with previous extrathoracic malignancies than patients without (5-year survival rates, 75.3% vs 82.7%; P = .009), although recurrence was not frequently seen (5-year recurrence-free rates, 78.7% vs 83.0%; P = .491).

Conclusions: Because treatment history of extrathoracic malignancy was not associated with postsurgical lung cancer recurrence, proposing curative resection could be justifiable if the previous cancer is deemed cured or controlled. However, the results showing that patients with previous cancer history have a worse survival rate than patients without should be taken into account when curative surgery is considered.
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http://dx.doi.org/10.1016/j.athoracsur.2019.06.074DOI Listing
December 2019

Venous thromboembolism prophylaxis in thoracic surgery patients: an international survey.

Eur J Cardiothorac Surg 2020 02;57(2):331-337

Department of Surgery, Boston University School of Medicine, Boston, MA, USA.

Objectives: Venous thromboembolic events (VTE) after thoracic surgery (TS) can be prevented with mechanical and chemical prophylaxis. Unlike other surgical specialties, TS lacks evidence-based guidelines. In the process of developing these guidelines, an understanding of the current prophylaxis methods practiced internationally is necessary and is described in this article.

Methods: A 26-item survey was distributed to members of the European Society of Thoracic Surgeons (ESTS), American Association of Thoracic Surgery (AATS), Japanese Association for Chest Surgery (JACS) and Chinese Society for Thoracic and Cardiovascular Surgery (CSTCS) electronically or in person. Participants were asked to report their current prophylaxis selection, timing of initiation and duration of prophylaxis, perceived risk factors and the presence and adherence to institutional VTE guidelines for patients undergoing TS for malignancies.

Results: In total, 1613 surgeons anonymously completed the survey with an overall 36% response rate. Respondents were senior surgeons working in large academic hospitals (≥70%, respectively). More than 83.5% of ESTS, AATS and JACS respondents report formal TS thromboprophylaxis protocols in their institutions, but 53% of CSTCS members report not having such a protocol. The regions varied in the approaches utilized for VTE prophylaxis, the timing of initiation perioperatively and the use and type of extended prophylaxis. Respondents reported that multiple risk factors and sources of information impact their VTE prophylaxis decision-making processes, and these factors vastly diverge regionally.

Conclusions: There is little agreement internationally on the optimal approach to thromboprophylaxis in the TS population, and guidelines will be helpful and vastly welcomed.
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http://dx.doi.org/10.1093/ejcts/ezz191DOI Listing
February 2020

Differences Between Patients With Idiopathic Pleuroparenchymal Fibroelastosis and Those With Other Types of Idiopathic Interstitial Pneumonia in Candidates for Lung Transplants.

Transplant Proc 2019 Jul - Aug;51(6):2014-2021. Epub 2019 Jul 11.

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

Introduction: The prognostic implications of having patients with idiopathic pleuroparenchymal fibroelastosis (IPPFE) on lung transplantation waiting lists have been unclear. In Japan, where a severe shortage of brain-dead donors remains a major limitation for organ transplantation, it is particularly important to predict the prognoses of patients when they are listed for transplantation. The purpose of this study was to investigate the characteristics of lung transplantation candidates with IPPFE and the influence of those characteristics on prognosis.

Methods: This was a retrospective review of 29 consecutive adult lung transplant candidates with idiopathic interstitial pneumonia between January 2014 and April 2018.

Results: Eight patients with IPPFE and 21 with other types of idiopathic interstitial pneumonia were included. Body mass index (median 17.1 kg/m vs 23.5 kg/m, P < .01) and ratio of anteroposterior to transverse diameter of the thoracic cage were significantly lower (0.530 vs 0.583, P = .02) in the IPPFE group. Patients with a body mass index <20.0 kg/m (P = .02), 6-minute walk distance <250.0 m (P < .01), ratio of PaO to fraction of inspiratory oxygen <300.0 mm Hg (P < .01), and an inability to perform the diffusing capacity of carbon monoxide test (P < .01) had significantly shorter survival times in the other idiopathic interstitial pneumonia, but not in the IPPFE, group. Some patients with IPPFE survived for long enough to undergo transplantation.

Conclusions: Patients with IPPFE waiting for transplantation have some distinctive characteristics and should be retained on waiting lists to receive transplants.
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http://dx.doi.org/10.1016/j.transproceed.2019.04.035DOI Listing
November 2019

Spread through air spaces is an independent predictor of recurrence in stage III (N2) lung adenocarcinoma.

Interact Cardiovasc Thorac Surg 2019 09;29(3):442-448

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

Objectives: Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma.

Methods: We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival.

Results: Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P < 0.001), papillary components (P < 0.001) and micropapillary components (P < 0.001). STAS was also significantly associated with recurrence (5-year recurrence-free probability: 19.0% vs 46.1%, P < 0.05). Univariate analyses showed that STAS was a significant risk factor for recurrence (hazard ratio 1.94, 95% confidence interval 1.07-3.51; P = 0.029).

Conclusions: The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.
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http://dx.doi.org/10.1093/icvts/ivz116DOI Listing
September 2019

Influence of Smoking and Histologic Subtype on Developing Extrathymic Malignancy in Thymoma Patients.

Ann Thorac Surg 2019 05 18;107(5):1532-1539. Epub 2018 Dec 18.

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

Background: Patients with thymomas are at high risk of developing extrathymic malignancies. We investigated the impact of extrathymic malignancies on the prognosis of patients with thymoma who underwent surgery and the risk factors for postoperative extrathymic malignancies.

Methods: A multicenter retrospective review of 252 patients who underwent surgical resection of thymomas from January 1977 to March 2016 was conducted. The exclusion criteria were recurrent thymoma, rare types of thymoma, and missing data. The overall number and incidence of extrathymic malignancies were calculated. Potential predictors of extrathymic malignancies were also evaluated.

Results: Two hundred twenty-eight patients were analyzed. Fifty-five extrathymic malignancies were observed (23 postoperative, 8 synchronous, and 24 preoperative). Among the overall cohort, the incidence of extrathymic malignancies significantly increased the patients' risk of death (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.72 to 9.40; p < 0.01). Among patients aged less than 70 years, the incidence of extrathymic malignancies was an independent risk factor for death. The incidence of postoperative extrathymic malignancies was significantly higher in patients with indolent forms of thymoma (type A/AB/B1) than aggressive forms (type B2/B3) (p = 0.02). In the multivariate analysis, indolent forms of thymoma (type A/AB/B1) (HR, 4.03; 95% CI, 1.12 to 14.6, p = 0.03) and a history of ever having smoked (HR, 5.29; 95% CI, 1.30 to 21.6; p = 0.02) were significant risk factors for the cumulative incidence of postoperative extrathymic malignancies.

Conclusions: Extrathymic malignancies increased the risk of death in patients with thymomas. Indolent forms of thymoma and a history of ever having smoked were risk factors for postoperative extrathymic malignancies.
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http://dx.doi.org/10.1016/j.athoracsur.2018.11.038DOI Listing
May 2019

Reply to Deng et al.

Eur J Cardiothorac Surg 2019 08;56(2):420-424

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

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http://dx.doi.org/10.1093/ejcts/ezy436DOI Listing
August 2019

[Role of Perioperative Extracorporeal Membrane Oxygenation in Cardiothoracic Surgery].

Kyobu Geka 2018 09;71(10):729-732

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

Extracorporeal membrane oxygenation (ECMO) is a temporary mode of providing life support by totally/partially augmenting heart and lung function over a few days to weeks. More than 30,000 cases involving ECMO usage in adults have been reported worldwide since the introduction of this unique therapy, and its applications continue to evolve rapidly. In recent times, ECMO plays a key role not only in the domain of critical care in intensive care units, but is also useful in the field of cardiothoracic surgery;it provides cardiopulmonary support intra- and post-operatively, respiratory support for primary graft dysfunction after lung transplantation and serves as a bridge to lung transplantation. The purpose of this review is to analyze the indications, modes of application, and complications of ECMO use in the field of cardiothoracic surgery.
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September 2018

Low truncal muscle area on chest computed tomography: a poor prognostic factor for the cure of early-stage non-small-cell lung cancer†.

Eur J Cardiothorac Surg 2019 Mar;55(3):414-420

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

Objectives: Depletion in skeletal muscle is closely associated with limited physical ability and high mortality. In this study, we evaluated the prognostic significance of skeletal muscle depletion in patients with early-stage non-small-cell lung cancer.

Methods: A retrospective analysis of patients with pathological stages I-II lung cancer, who underwent curative resection between 2009 and 2013, was conducted. The truncal muscle index (TMI) (area/height2) at the first lumbar vertebral level was measured by preoperative axial computed tomography. Overall survival and recurrence-free survival were compared between the lowest gender-specific quartile of the TMI and the other quartiles.

Results: A total of 314 subjects were included in the study. The cumulative 5-year recurrence-free and overall survival rates were significantly shorter in patients with lower TMIs (69% vs 83.5%, P = 0.028; 64.8% vs 80.1%, P = 0.003, respectively). In multivariable models, the TMI was identified as an independent prognostic factor for overall survival (P =  0.017, hazard ratio 1.84, 95% confidence interval 1.12-3.05), after adjusting for age, gender, preoperative serum albumin, carcinoembryonic antigen, neutrophil to lymphocyte ratio and pathological stage.

Conclusions: A low preoperative TMI was associated with a poor postoperative outcome in patients with early-stage non-small-cell lung cancer. This factor may be included in the preoperative assessment of patients, for whom surgical intervention is considered.
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http://dx.doi.org/10.1093/ejcts/ezy324DOI Listing
March 2019

High CCR4 expression in the tumor microenvironment is a poor prognostic indicator in lung adenocarcinoma.

J Thorac Dis 2018 Aug;10(8):4741-4750

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

Background: Clinical trials of anti-CCR4 antibody for solid cancers with or without other immune-modulating agents including immune checkpoint blockade therapy are currently underway. However, little is known about the roles of CCR4 lymphocytes and their prognostic impact in lung cancer. We hypothesized that high CCR4 expression in the tumor microenvironment would be associated with a poor prognosis and would act as a biomarker in lung adenocarcinoma.

Methods: First, the prognostic impact of gene expression was explored using pooled data from public transcriptomic databases with online survival analysis software. Second, tissue microarrays (TMAs) were constructed from resected lung adenocarcinoma specimens from tumors up to 3 cm in size. The density of CCR4 lymphocytes infiltrating the tumor was then assessed by immunohistochemistry and related to survival. Confounding factors were controlled for by multivariate analysis using the Cox proportional hazards model.

Results: Higher than median expression of the gene was identified as an independent poor prognostic factor for overall survival (OS) by multivariate analysis of 720 lung adenocarcinoma patients in the public databases [HR =1.55 (95% CI: 1.03-2.35), P=0.037]. Consistent with this, high CCR4 tumor-infiltrating lymphocyte (TIL) density was found to be an independent poor prognostic factor for both OS [HR =2.24 (1.01-5.34), P=0.049] and recurrence-free survival (RFS) [HR =2.20 (1.16-4.39), P=0.017] in the patients from whom TMA were obtained (n=180). Age, male gender, predominantly non-lepidic histological subtype, nodal involvement, and low CD8 TIL density were also independent poor prognostic factors. However, gene expression and Foxp3 lymphocyte infiltration did not possess any prognostic value in either study.

Conclusions: High CCR4 expression in the tumor microenvironment may be a poor prognostic factor in lung adenocarcinoma. Patients with high CCR4 lymphocyte infiltration may have a poor prognosis and thus be suitable candidates for clinical trials of anti-CCR4 antibody treatment.
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http://dx.doi.org/10.21037/jtd.2018.07.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129889PMC
August 2018

Impact of the 8th Edition of the UICC-TNM Classification on Clinical Stage 0-IA Lung Adenocarcinoma: Does the New Classification Predict Postoperative Prognosis More Precisely than the Previous One?

Ann Thorac Cardiovasc Surg 2018 Oct 30;24(5):223-229. Epub 2018 May 30.

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

Purpose: Early lung adenocarcinoma has been more frequently found recently. The 8th edition of the Union for International Cancer Control (UICC)-Tumor Node Metastasis (TNM) classification for lung cancer has been effective since January 2017. This study aims to elucidate advantages of the current classification for patients with clinical stage 0-IA lung adenocarcinoma, in comparison with the older one.

Methods: We retrospectively reviewed the data of clinical stage IA (7th edition) lung adenocarcinoma patients who underwent surgery at our institute from 2001 to 2012, and reclassified them by the 8th edition. Survival analysis was used to evaluate the impact of the two classifications.

Results: In all, 281 cases were eligible. Clinical T-factors (8th) were significant prognostic factors for overall survival (P = 0.001), recurrence-free survival (P <0.001), and cancer-specific survival (P = 0.001). However, those in the previous edition were not (P = 0.894, P = 0.144, and P = 0.822, respectively).

Conclusion: The 8th edition of the UICC-TNM classification predicts postoperative prognosis more precisely than the 7th one in clinical stage 0-IA lung adenocarcinoma. It is probably because the stage distribution of the population, which included in the research project the 8th edition based on, has been changed, and the new edition develops more accurate staging criteria for ground-glass nodule (GGN).
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http://dx.doi.org/10.5761/atcs.oa.18-00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197998PMC
October 2018

Secondary Chondrosarcoma Presenting with Symptoms Similar to Thoracic Outlet Syndrome.

Case Rep Orthop 2018 12;2018:9347145. Epub 2018 Mar 12.

Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.

Thoracic outlet syndrome (TOS) is caused by heterogeneous factors that compress the brachial plexus and subclavian artery; tumor is rarely a cause of TOS. Here, we present the case of a 26-year-old man with secondary chondrosarcoma arising from osteochondroma of the left clavicle causing TOS, with a direct compression of the brachial plexus and subclavian artery. Immediately after surgery, the symptoms of TOS reduced. To our knowledge, this is the first case of a secondary chondrosarcoma of the clavicle causing TOS, which is possibly the key symptom for diagnosing malignant transformation of osteochondroma of the clavicle.
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http://dx.doi.org/10.1155/2018/9347145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867559PMC
March 2018

Prognostic significance of the preoperative neutrophil-to-lymphocyte ratio for complete resection of thymoma.

Surg Today 2018 Apr 23;48(4):422-430. Epub 2017 Oct 23.

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

Purpose: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with a poor prognosis for various cancers. We evaluated the prognostic role of the preoperative NLR in patients with thymoma.

Methods: We reviewed the medical records of 254 patients who underwent resection of thymic epithelial tumors at our institution. Patients were excluded if they had received steroid therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was measured preoperatively, and outcomes of patients with a low (< 1.96) vs those with a high (≥ 1.96) NLR were compared statistically.

Results: Of 159 eligible patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS), disease-related survival (DRS), and the cumulative incidence of recurrence (CIR) differed significantly between the groups. Multivariate analyses revealed that a high NLR was independently associated with disease-related survival and a cumulative incidence of recurrence. A high NLR was also associated with a higher risk of recurrence of Masaoka stage I or II thymoma.

Conclusions: An elevated preoperative NLR was associated with poor outcomes after thymoma resection. Thus, the NLR may be a useful biomarker of the postoperative prognosis of thymoma.
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http://dx.doi.org/10.1007/s00595-017-1602-yDOI Listing
April 2018

Squamous cell carcinoma of the lung showing a ground glass nodule on high-resolution computed tomography associated with pneumoconiosis: a case report.

Surg Case Rep 2017 Sep 29;3(1):107. Epub 2017 Sep 29.

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

Background: Adenocarcinoma with lepidic growth pattern presents as a ground glass nodule (GGN) on high resolution computed tomography (CT), whereas peripheral pulmonary squamous cell carcinoma (SCC) usually presents as a solid nodule. We herein report a rare case of pulmonary SCC extending along the alveolar lumen representing as a GGN on a CT scan in a patient with pneumoconiosis.

Case Presentation: A 77-year-old man with pneumoconiosis was found to have a gradually enlarging GGN in the right lower lobe of the lung on CT. An adenocarcinoma of the lung was suspected. The GGN was successfully resected by thoracoscopic segmentectomy. Pathological examination of the resected specimen was pathologically diagnosed as a stage IA SCC extending along the alveolar lumen. The patient had no evidence of recurrence 19 months after surgery.

Conclusions: SCC should be included in the differential diagnosis of peripherally located GGNs, especially in patients at high risk of SCC of the lung such as those with pneumoconiosis.
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http://dx.doi.org/10.1186/s40792-017-0384-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622012PMC
September 2017

Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins.

Sci Rep 2017 09 14;7(1):11607. Epub 2017 Sep 14.

Department of Virology 3, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo, 208-0011, Japan.

Rubella virus (RV) generally causes a systemic infection in humans. Viral cell tropism is a key determinant of viral pathogenesis, but the tropism of RV is currently poorly understood. We analyzed various human cell lines and determined that RV only establishes an infection efficiently in particular non-immune cell lines. To establish an infection the host cells must be susceptible and permissible. To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1). VSV-RV/CE2E1 entered cells in an RV envelope protein-dependent manner, and thus the infection was neutralized completely by an RV-specific antibody. The infection was Ca-dependent and inhibited by endosomal acidification inhibitors, further confirming the dependency on RV envelope proteins for the VSV-RV/CE2E1 infection. Human non-immune cell lines were mostly susceptible to VSV-RV/CE2E1, while immune cell lines were much less susceptible than non-immune cell lines. However, susceptibility of immune cells to VSV-RV/CE2E1 was increased upon stimulation of these cells. Our data therefore suggest that immune cells are generally less susceptible to RV infection than non-immune cells, but the susceptibility of immune cells is enhanced upon stimulation.
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http://dx.doi.org/10.1038/s41598-017-10865-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599607PMC
September 2017

[Critical Care Managements after Lung Transplantation].

Authors:
Masaki Anraku

Kyobu Geka 2017 07;70(8):701-707

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

Lung transplantation is a viable treatment option for patients with end-stage lung diseases such as interstitial pneumonia/pulmonary fibrosis, emphysema, pulmonary hypertension, and so on. Collecting available clinical, physiological, serological, and surgical information of both donor and recipient is vital when planning relevant postoperative managements. The goal of the managements is to keep the transplanted lung (s) functional while preventing/treating infection, rejection, and ischemiareperfusion lung injury. Immunosuppressive therapy, anti-mycobacterial/viral therapy, and cardio-pulmonary supports should be optimized without causing unfavorable side-effects that can lead to kidney, liver, digestive and neurological malfunction. During the post-transplant intensive care period, satisfying the endorgan oxygen requirement is the key to maintain vital organ stability. Aggressive rehabilitation should be utilized as soon as the hemodynamic status allows it. Deep venous thrombosis and subsequent pulmonary embolism should be prevented by giving anti-coagulants and active mobilization, because the incidence could be underrecognized. Avoiding multifactorial allograft injuries can improve not only short-term graft function, but also long-term patients' outcome after lung transplantation.
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July 2017

A deep azygoesophageal recess may increase the risk of secondary spontaneous pneumothorax.

Surg Today 2017 Sep 15;47(9):1147-1152. Epub 2017 Feb 15.

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

Purpose: The azygoesophageal recess (AER) is known as a possible cause of bulla formation in patients with spontaneous pneumothorax. However, there has been little focus on the depth of the AER. We evaluated the relationship between the depth of the AER and pneumothorax development.

Methods: We conducted a retrospective study of 80 spontaneous pneumothorax patients who underwent surgery at our institution. We evaluated the depth of the AER on preoperative computed tomography scans.

Results: Ruptured bullae at the AER were found in 12 patients (52.2%) with secondary spontaneous pneumothorax (SSP) and 8 patients (14.0%) with primary spontaneous pneumothorax (PSP) (p < 0.001). In patients with ruptured bullae at the AER, 10 SSP patients (83.3%) had a deep AER while only 2 PSP patients (25%) had a deep AER (p = 0.015).

Conclusions: A deep AER was more frequently associated with SSP than with PSP. A deep AER may contributes to bulla formation and rupture in SSP patients.
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http://dx.doi.org/10.1007/s00595-017-1482-1DOI Listing
September 2017

Prognostic significance of red cell distribution width in elderly patients undergoing resection for non-small cell lung cancer.

J Thorac Dis 2016 Dec;8(12):3658-3666

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

Background: The impact of red cell distribution width (RDW) on outcomes in elderly patients after surgery for non-small cell lung cancer (NSCLC) is not fully understood.

Methods: We retrospectively analyzed 992 NSCLC patients who underwent curative resection between 1998 and 2012. The following variables were included in the analyses to evaluate the role of RDW: age, gender, smoking index, leukocyte count, neutrophil to lymphocyte ratio (NLR), hemoglobin, platelet count, albumin, C-reactive protein, carcinoembryonic antigen, respiratory function, histology, T factor, N factor, surgical approach, surgical procedures, complications and prognosis.

Results: High RDW (>13.8) was an independent risk factor for morbidity [hazard ratio (HR) 2.1; P<0.01], recurrence (HR 2.0; P=0.01), overall survival (OS) (HR 2.1; P<0.01) and disease-free survival (DFS) (HR 2.0; P<0.01) in elderly patients (age ≥75 years, n=275), whereas it was not in younger patients (age <75 years, n=717). The surgical outcome was extremely poor in those older than 80 years with a RDW greater than 15% (morbidity, 56%; postoperative stay, 23 days; OS, 24%; DFS, 0%). RDW was unaffected by age (R =0.01; P=0.86) and elevated RDW without anemia was more prognostic than high RDW due to anemia in elderly patients.

Conclusions: High RDW was significantly associated with high morbidity and reduced survival in elderly patients who underwent resection for NSCLC. Therefore, this parameter should be taken into account when surgery is considered in the elderly.
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http://dx.doi.org/10.21037/jtd.2016.12.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227271PMC
December 2016

The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.

Nat Commun 2017 01 30;8:14259. Epub 2017 Jan 30.

Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.

Diverse cellular proteins and RNAs are tightly regulated in their subcellular localization to exert their local function. Here we report that the tumour suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of human immunodeficiency virus (HIV)-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. A proteomic analysis and subsequent biomolecular interaction assay reveals that the carboxyl terminus of APC interacts with the matrix region of Gag. Ectopic expression of APC, but not its familial adenomatous polyposis-related truncation mutant, prominently enhances HIV-1 production. Conversely, the depletion of APC leads to a significant decrease in membrane targeting of viral components, resulting in the severe loss of production of infectious virions. Furthermore, APC promotes the directional assembly of viral components at virological synapses, thereby facilitating cell-to-cell viral transmission. These findings reveal an unexpected role of APC in the directional spread of HIV-1.
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http://dx.doi.org/10.1038/ncomms14259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290283PMC
January 2017

An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer.

J Thorac Oncol 2017 05 11;12(5):791-803. Epub 2017 Jan 11.

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

Introduction: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing.

Methods: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma). Mutated neoantigens and cancer germline antigens expressed in the tumor were assessed for predicted binding to patients' human leukocyte antigen molecules. The expression of genes related to cancer immunity was assessed and normalized to construct a radar chart composed of eight axes reflecting seven steps in the cancer-immunity cycle.

Results: Three immunogram patterns were observed in patients with lung cancer: T-cell-rich, T-cell-poor, and intermediate. The T-cell-rich pattern was characterized by gene signatures of abundant T cells, regulatory T cells, myeloid-derived suppressor cells, checkpoint molecules, and immune-inhibitory molecules in the tumor, suggesting the presence of antitumor immunity dampened by an immunosuppressive microenvironment. The T-cell-poor phenotype reflected lack of antitumor immunity, inadequate dendritic cell activation, and insufficient antigen presentation in the tumor. Immunograms for both the patients with adenocarcinoma and the patients with nonadenocarcinoma tumors included both T-cell-rich and T-cell-poor phenotypes, suggesting that histologic type does not necessarily reflect the cancer immunity status of the tumor.

Conclusions: The patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.
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http://dx.doi.org/10.1016/j.jtho.2017.01.005DOI Listing
May 2017

Role of post-mapping computed tomography in virtual-assisted lung mapping.

Asian Cardiovasc Thorac Ann 2017 Feb 11;25(2):123-130. Epub 2017 Jan 11.

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

Background Virtual-assisted lung mapping is a novel bronchoscopic preoperative lung marking technique in which virtual bronchoscopy is used to predict the locations of multiple dye markings. Post-mapping computed tomography is performed to confirm the locations of the actual markings. This study aimed to examine the accuracy of marking locations predicted by virtual bronchoscopy and elucidate the role of post-mapping computed tomography. Methods Automated and manual virtual bronchoscopy was used to predict marking locations. After bronchoscopic dye marking under local anesthesia, computed tomography was performed to confirm the actual marking locations before surgery. Discrepancies between marking locations predicted by the different methods and the actual markings were examined on computed tomography images. Forty-three markings in 11 patients were analyzed. Results The average difference between the predicted and actual marking locations was 30 mm. There was no significant difference between the latest version of the automated virtual bronchoscopy system (30.7 ± 17.2 mm) and manual virtual bronchoscopy (29.8 ± 19.1 mm). The difference was significantly greater in the upper vs. lower lobes (37.1 ± 20.1 vs. 23.0 ± 6.8 mm, for automated virtual bronchoscopy; p < 0.01). Despite this discrepancy, all targeted lesions were successfully resected using 3-dimensional image guidance based on post-mapping computed tomography reflecting the actual marking locations. Conclusions Markings predicted by virtual bronchoscopy were dislocated from the actual markings by an average of 3 cm. However, surgery was accurately performed using post-mapping computed tomography guidance, demonstrating the indispensable role of post-mapping computed tomography in virtual-assisted lung mapping.
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http://dx.doi.org/10.1177/0218492316689351DOI Listing
February 2017

Mediastinal seminoma associated with multilocular thymic cyst.

Surg Case Rep 2017 Dec 5;3(1). Epub 2017 Jan 5.

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

An asymptomatic 26-year-old man received an annual medical check-up, and chest X-ray showed a protrusion of the aortopulmonary window. Chest computed tomography (CT) revealed an anterior mediastinal tumor and cysts with thin wall and septum enhancement. The preoperative diagnosis was cystic thymoma or malignant lymphoma. We performed total resection of the tumor through a median sternotomy. The pathological findings revealed seminoma, positive for c-kit stain, and multilocular thymic cysts. Cysts were lined by normal squamous epithelium and no seminoma cells were located on their surface. So, cysts were probably secondary changes caused by seminoma cells themselves or inflammatory stimulations. No invasion to adjacent structures was seen. After the surgery, testicular ultrasound imaging and abdominal, pelvic, and cerebral CT showed no apparent tumor or enlarged lymph nodes; however, an abnormal uptake in the right mesenteric lymph node was pointed out by F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan. The patient received four courses of bleomycin, etoposide, and cisplatin (BEP) as adjuvant chemotherapy. Follow-up PET scan revealed no uptake in the right mesenteric lymph node. To date, no recurrence or metastasis has been identified for 16 months.
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http://dx.doi.org/10.1186/s40792-016-0278-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215007PMC
December 2017
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