Faculty Profiles - CHEN-YOSHIKAWA Toyofumi

Papers - CHEN-YOSHIKAWA Toyofumi

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Difficult preoperative diagnosis of multiple mediastinal cholesterol granulomas: a case report

Takada Yuri, Nakamura Shota, Chen-Yoshikawa Toyofumi Fengshi, Sugiyama Tomoshi

The Journal of the Japanese Association for Chest Surgery Vol. 39 ( 1 ) page： 34 - 39 2025.1

Language：Japanese Publisher：The Japanese Association for Chest Surgery

<p>A 55-year-old man was found to have chest radiographic abnormalities during a routine health examination. Chest computed tomography revealed multiple nodules in the upper and anterior mediastinum. Because of the presence of multiple nodules, we suspected simultaneous multiple thymoma, thymoma with lymph node metastasis, or malignant lymphoma. Computed tomography-guided percutaneous needle biopsy was performed, but the tissue was very hard and a specimen could not be extracted. Therefore, we performed total thymectomy and resection of the surrounding multiple nodules for diagnostic and therapeutic purposes. The postoperative histopathological diagnosis was multiple cholesterol granulomas. Multiple cholesterol granulomas in the mediastinum are rare. There are no reports of preoperative biopsy. We herein report a rare case of mediastinal cholesterol granulomas with extremely hard tissue that could not be obtained by computed tomography-guided percutaneous needle biopsy despite showing soft tissue shadows without calcification and suggesting solid tumors.</p>

DOI： 10.2995/jacsurg.39.34

CiNii Research

Managing recurrent thymic epithelial tumors after resection: outcomes and role of re-resection

Mizuno T., Chen-Yoshikawa T.F.

Mediastinum Vol. 8 2024.12

Publisher：Mediastinum

Thymic epithelial tumors (TETs) are rare neoplasms that include thymomas, thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs). These three tumor categories differ in aggressiveness, the incidence of recurrence after resection, the pattern of recurrence, and survival outcomes. Owing to the tumor’s rarity, randomized trials have not been performed in the initial treatment setting. Furthermore, such trials have never been performed in recurrent cases after the initial resection. Thymomas have indolent characteristics, with a wide range of biological spectra compared to TCs and TNENs; therefore, several authors have reported favorable outcomes after re-resection for recurrent thymomas. Common recurrent sites are the local site and pleura, and recurrent disease progresses slowly after detection. Additionally, long-term survivors are sometimes observed after recurrence, and whether re-resections contribute to post-recurrent and cause-specific survival remains unclear. Multimodal therapies are indicated in patients with locally or regionally advanced recurrence, similar to those performed in the initial treatment settings. TCs and TNENs exhibit more aggressive behavior than thymomas. Surgical resection was performed on selected patients who experienced recurrence. Currently, there are no guidelines on selecting patients for re-resection. Therefore, it is most likely that each physician selects based on favorable factors, including the extent of disease, disease-free intervals, and histology. No evidence of nonsurgical treatments, such as radiotherapy or chemotherapy, has yet to be established. This review article summarizes the limited evidence on managing recurrent TETs after resection compared to thymomas, TCs, and TNENs, focusing on re-resection.

DOI： 10.21037/med-24-26

Scopus

Adjuvant Chemotherapy Decisions in the Treatment of Lung Cancer Considering Nonrelapse Mortality: A Multicenter Study. International journal

Mitsue Kawahara, Yosuke Matsuura, Shota Nakamura, Fumie Kinoshita, Keiju Aokage, Tetsuhiko Asao, Toyofumi Fengshi Chen-Yoshikawa, Mingyon Mun

Clinical lung cancer 2024.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Adjuvant chemotherapy (Adj) reduces recurrence and improves long-term survival in patients with surgically resected lung cancer. However, it has minimal impact on patients who die without relapsing. To optimize Adj indications, we aimed to identify factors associated with nonrelapse mortality (NRM). PATIENTS AND METHODS: This multicenter, retrospective, observational study enrolled patients with surgically resected with stages II-III non-small cell lung cancer. Multivariable Cox regression analysis was performed to identify the factors associated with NRM and early-NRM within 2 years of surgery and to stratify the enrolled patients. Adj administration rates and postoperative overall and recurrence-free survival rates were compared. Multivariable competing regression analysis with NRM as a competing risk was used to assess the cumulative incidence of lung cancer-associated death and recurrence. RESULTS: Through a scoring system assigning 1 point to each extracted factor (old age, male sex, poor performance status, nonadenocarcinoma, and occurrence of major complications), the 1,244 included patients were stratified into 3 groups based on scores of 0-5: A (0-1 points; n = 613), B (2-3 points; n = 549), and C (4-5 points; n = 62) with 53%, 26%, and 11% Adj administration, respectively. Although group A showed the highest overall and recurrence-free survival rates, competing regression analysis showed no significant differences in cumulative lung cancer-associated death and recurrence incidence between the groups. CONCLUSION: Better prognosis in group A was attributed to lower NRM and higher Adj administration rates. While proactive Adj may benefit group A, careful evaluation is warranted for group C to optimize Adj indication.

DOI： 10.1016/j.cllc.2024.12.009

Scopus

PubMed

症例感染巣切除後に再燃予防に抗真菌薬を投与した肺クリプトコッカス症の1例

藤村崇生, 中村彰太, 桐山亮太, 親松裕典, 岡川武日児, 深見惇, 新美誠次郎, 芳川豊史

胸部外科 Vol. 77 ( 13 ) page： 1135 - 1140 2024.12

[Pulmonary Cryptococcosis Treated with Antifungal Drugs After Surgical Resection:Report of a Case].

Takaki Fujimura, Shota Nakamura, Ryota Kiriyama, Hironori Oyamatsu, Takehiko Okagawa, Jun Fukami, Sejiro Niimi, Toyofumi Fengshi Chen-Yoshikawa

Kyobu geka. The Japanese journal of thoracic surgery Vol. 77 ( 13 ) page： 1135 - 1140 2024.12

Language：Japanese Publishing type：Research paper (scientific journal)

The patient is an 81-year-old man. He underwent surgery for pancreatic body cancer in 201X and was followed up every six months with computed tomography (CT) imaging. A CT scan in 201X+5 showed a new nodule in S6 of the right lung. The nodule grew in the latter half of the year and was diagnostically resected on suspicion of being a metastatic lung tumor. A histopathological examination of the resected lung revealed pulmonary cryptococcosis. The postoperative course was uneventful, and the patient was treated with fluconazole 200 mg/day for six months. The patient is currently alive and recurrence-free three years after surgery. Pulmonary cryptococcosis can recur and may be complicated by meningitis. Postoperative antifungal therapy should be considered because of the poor prognosis of meningitis. Postoperative treatment should be performed with caution, especially in patients who are susceptible to infection, have positive preoperative serum cryptococcal antigen levels or have a high standardized uptake value (SUV) max on positron emission tomography (PET)-CT scanning, and are considered to have high fungal loads or activity.

PubMed

Blood eosinophil count correlates with alveolar damage in emphysema-predominant COPD

Nakamura S., Wakahara K., Majima S., Yokoi E., Fukutani E., Otsuki R., Iwano S., Chen-Yoshikawa T.F., Kinoshita F., Abe T., Sashio T., Kimura T., Izuhara K., Hashimoto N., Ishii M., Hasegawa Y.

BMC Pulmonary Medicine Vol. 24 ( 1 ) 2024.12

Publisher：BMC Pulmonary Medicine

Background: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes. Methods: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin) and thick airway wall (WT thick) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens. Results: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls. Conclusions: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall.

DOI： 10.1186/s12890-024-03320-2

Scopus

綜説小児の肺移植の現状と未来

芳川豊史

小児科 Vol. 65 ( 11 ) page： 1155 - 1163 2024.11

A case of peribronchiolar metaplasia of the lung appearing as a solid nodule on computed tomography.

Yuri Takada, Shota Nakamura, Yoshito Imamura, Shoji Okado, Yuji Nomata, Hiroki Watanabe, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Tetsuya Mizuno, Iori Kojima, Toyofumi Fengshi Chen-Yoshikawa

Nagoya journal of medical science Vol. 86 ( 4 ) page： 720 - 725 2024.11

Language：English Publishing type：Research paper (scientific journal)

Peribronchiolar metaplasia is an uncommon lesion characterized by fibrosis and bronchiolar epithelial cell proliferation along the peribronchiolar alveolar walls, primarily in response to bronchiolar and peribronchiolar injuries. Peribronchiolar metaplasia usually appears as ground glass nodules or sub-solid nodules on computed tomography. However, we present an exceptional case of peribronchiolar metaplasia that appeared as a solitary solid nodule on computed tomography. A 62-year-old woman with conjunctival icterus was diagnosed with ampullary cancer and nodal metastasis. A solid predominant nodule (0.7 cm maximum diameter) in the left lower lobe was identified on computed tomography, requiring accurate differentiation between primary lung cancer and pulmonary metastasis. Due to the location, histological confirmation via transbronchial biopsy was not feasible. Hence, the patient underwent surgery for both diagnosis and treatment. The pathological findings revealed the growth of columnar epithelium containing ciliated cells replacing alveolar epithelium in the bronchioloalveolar wall with no malignant component. The final pathological diagnosis of the lesion was peribronchiolar metaplasia. This unique case highlights an atypical presentation of peribronchiolar metaplasia as a solitary solid nodule on computed tomography. Recognizing that peribronchiolar metaplasia can also manifest as solid nodules, as illustrated in our current case, is essential.

DOI： 10.18999/nagjms.86.4.720

Scopus

PubMed

Impact of the expanded indication of robot-assisted thoracic surgery for mediastinal tumors.

Taketo Kato, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

General thoracic and cardiovascular surgery 2024.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Following the introduction of robot-assisted thoracoscopic surgery (RATS) as a health insurance-covered treatment in Japan, we investigated the current status and impact of the expansion of the indications for RATS for mediastinal tumors. METHODS: Between 2018 and 2022, 209 cases of total mediastinal tumor resection were performed in our hospital. The study period was divided into the first half (January 2018 to June 2020) and the second half (July 2020 to December 2022), and perioperative parameters were compared between the two groups. RESULTS: Ninety-six surgical procedures were performed in the first half and 113 in the second half. The percentage of RATS approach was significantly higher in the second half compared with the first half (P < 0.001). Indications for RATS in the second half compared with the first half were significantly increased in patients with stage II (P < 0.001) and stage III (P = 0.026) thymomas, tumor diameter ≥ 50 mm (P < 0.011), and patients undergoing extended thymectomy for myasthenia gravis (P < 0.009). In respect of short-term postoperative parameters, the estimated intraoperative blood loss (P < 0.035), postoperative drain duration (P < 0.037), and postoperative hospital stay (P < 0.011) were significantly lower in the second half than in the first half. CONCLUSIONS: RATS has recently been expanded for mediastinal tumors with improved short-term outcomes in our hospital after health insurance was applied in Japan. In the future, it will be necessary to discuss the further expansion of its indications by taking into account safety and long-term outcomes.

DOI： 10.1007/s11748-024-02093-z

Scopus

PubMed

Virtual thoracoscopic imaging for accurate pulmonary nodule localization: clinical experience.

Yuka Kadomatsu, Megumi Nakao, Shoji Okado, Harushi Ueno, Taketo Kato, Shota Nakamura, Toyofumi Fengshi Chen-Yoshikawa

Surgery today 2024.10

Language：English Publishing type：Research paper (scientific journal)

The increasing detection of small pulmonary nodules on computed tomography (CT) warrants simple and effective nodule localization methods. We describe our clinical experience using an experimental computer that displays virtual thoracoscopic images. This device constructs three-dimensional images from preoperative CT scans and simulates the deflated lung parenchyma in the lateral decubitus position. Five patients underwent lung resection using this technology. The device provided images that closely resembled actual thoracoscopic images in all cases. This method addresses the limitations of other localization techniques such as allergic reactions and mechanical marker-related complications. The method only requires preoperative CT images, and the process is semi-automatically performed by specifying the nodule location, thoracoscopic camera insertion site, and camera angle. This study is still in the preliminary phase and has several limitations. However, this method has the potential to accurately predict nodule locations and eliminate the many risks associated with other techniques.

DOI： 10.1007/s00595-024-02945-4

Scopus

PubMed

肺移植患者を取り巻く呼吸ケアの目標と実情

芳川豊史, 石塚全

日本呼吸ケア・リハビリテーション学会誌 Vol. 34 ( supplement ) page： 125s_2 - 125s_2 2024.10

Current Status and Future Perspectives of Preoperative and Intraoperative Marking in Thoracic Surgery. International journal

Toyofumi Fengshi Chen-Yoshikawa, Shota Nakamura, Harushi Ueno, Yuka Kadomatsu, Taketo Kato, Tetsuya Mizuno

Cancers Vol. 16 ( 19 ) 2024.9

Language：English Publishing type：Research paper (scientific journal)

The widespread implementation of lung cancer screening and thin-slice computed tomography (CT) has led to the more frequent detection of small nodules, which are commonly referred to thoracic surgeons. Surgical resection is the final diagnostic and treatment option for such nodules; however, surgeons must perform preoperative or intraoperative markings for the identification of such nodules and their precise resection. Historically, hook-wire marking has been performed more frequently worldwide; however, lethal complications, such as air embolism, have been reported. Therefore, several surgeons have recently attempted to develop novel preoperative and intraoperative markers. For example, transbronchial markings, such as virtual-assisted lung mapping and intraoperative markings using cone-beam computed tomography, have been developed. This review explores various marking methods that have been practically applied for a better understanding of preoperative and intraoperative markings in thoracic surgery. Recently, several attempts have been made to perform intraoperative molecular imaging and dynamic virtual three-dimensional computed tomography for the localization, diagnosis, and margin assessment of small nodules. In this narrative review, the current status and future perspectives of preoperative and intraoperative markings in thoracic surgery are examined for a better understanding of these techniques.

DOI： 10.3390/cancers16193284

Scopus

PubMed

2D/3D deformable registration for endoscopic camera images using self-supervised offline learning of intraoperative pneumothorax deformation Reviewed

Oya T., Kadomatsu Y., Chen-Yoshikawa T.F., Nakao M.

Computerized Medical Imaging and Graphics Vol. 116 2024.9

Language：English Publisher：Computerized Medical Imaging and Graphics

Shape registration of patient-specific organ shapes to endoscopic camera images is expected to be a key to realizing image-guided surgery, and a variety of applications of machine learning methods have been considered. Because the number of training data available from clinical cases is limited, the use of synthetic images generated from a statistical deformation model has been attempted; however, the influence on estimation caused by the difference between synthetic images and real scenes is a problem. In this study, we propose a self-supervised offline learning framework for model-based registration using image features commonly obtained from synthetic images and real camera images. Because of the limited number of endoscopic images available for training, we use a synthetic image generated from the nonlinear deformation model that represents possible intraoperative pneumothorax deformations. In order to solve the difficulty in estimating deformed shapes and viewpoints from the common image features obtained from synthetic and real images, we attempted to improve the registration error by adding the shading and distance information that can be obtained as prior knowledge in the synthetic image. Shape registration with real camera images is performed by learning the task of predicting the differential model parameters between two synthetic images. The developed framework achieved registration accuracy with a mean absolute error of less than 10 mm and a mean distance of less than 5 mm in a thoracoscopic pulmonary cancer resection, confirming improved prediction accuracy compared with conventional methods.

DOI： 10.1016/j.compmedimag.2024.102418

Scopus

特集低酸素に打ち克つ Ⅳ.低酸素に対する対処法-適応疾患と対処の実際肺移植 Invited

芳川豊史

呼吸器ジャーナル Vol. 72 ( 3 ) page： 478 - 484 2024.8

Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic Reviewed

Yamanaga S., Shimata K., Ohfuji S., Yoshikawa M., Natori Y., Hibi T., Yuzawa K., Egawa H., Unagami K., Ishida H., Omoto K., Kasahara M., Uchida H., Sakamoto S., Futamura K., Nishikawa K., Imamura R., Nakazawa S., Hatano E., Ito T., Masano Y., Nishihira M., Hirata Y., Sakuma Y., Onishi Y., Yokoyama N., Yamamoto S., Yamada Y., Ogura Y., Kurata N., Uchida J., Kabei K., Iwamoto H., Ikeda C., Shinoda K., Yoshiike M., Hotta K., Hidaka Y., Iwami D., Ishii Y., Kamiyama M., Yoshizumi T., Kosai-Fujimoto Y., Kobayashi T., Motoyama K., Yamamoto M., Asai T., Tasaki M., Kenmochi T., Ito T., Tokodai K., Fujio A., Tsukamoto Y., Watanabe T., Akamatsu N., Yamashina S., Ishii D., Kitajima K., Yamada Y., Mitsuke A., Sakaguchi T., Nakamura M., Tomita Y., Nakamura Y., Ishimoto T., Ohdan H., Tanimine N., Fujiwara T., Yanagihara M., Hatakeyama S., Takai M., Nose K., Kikuchi T., Mori Y., Araki M., Sekito T., Nishimura S., Tanabe T., Igarashi Y., Hidaka S., Watanabe M., Ariyoshi Y., Hasegawa Y., Kamiyama M., Yoneda T., Shimizu T., Nishikawa K., Fukumoto T., Kuramitsu K., Kato M., Saito M., Shinkai M., Usui H., Sato M., Eguchi H., Imamura H., Kobayashi S., Soejima Y., Mita A., Kobayashi T.

American Journal of Transplantation Vol. 24 ( 8 ) page： 1495 - 1508 2024.8

Language：English Publisher：American Journal of Transplantation

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

DOI： 10.1016/j.ajt.2024.03.016

Scopus

Efficacy of Immune Checkpoint Inhibitors in Postoperative Recurrence of Wild-type EGFR Non-Small Cell Lung Cancer. Reviewed International journal

Yoshito Imamura, Taketo Kato, Yuji Nomata, Shoji Okado, Hiroki Watanabe, Yuta Kawasumi, Keita Nakanishi, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Tetsunari Hase, Ichidai Tanaka, Makoto Ishii, Hiroshi Yatsuya, Toyofumi Fengshi Chen-Yoshikawa

Anticancer research Vol. 44 ( 8 ) page： 3451 - 3461 2024.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC), but specific outcomes of ICIs treatment among patients with postoperative recurrence of NSCLC remain unclear. The objective of the study was to compare the efficacy of ICIs and chemotherapy with conventional chemotherapy only in patients with postoperative recurrence of epidermal growth factor receptor (EGFR) wild-type NSCLC. PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent anatomical lung resection at the Nagoya University Hospital and were treated for postoperative recurrence of wild-type EGFR NSCLC. This study evaluated the prognosis for postoperative recurrence, including ICIs treatment and other clinicopathological factors. RESULTS: Of the 83 patients included in the analysis, 20 patients underwent chemotherapy and 63 patients underwent chemotherapy combined with ICIs. The combination of ICIs and chemotherapy significantly prolonged survival after recurrence (median survival: 33.1 months vs. 22.0 months, p=0.01). In the ICIs group, no significant differences in survival were detected between patients with different programmed death ligand 1 (PD-L1) status (Tumor Proportion Scores: <1%, 1%-49%, ≥50%, p=0.27). Multivariate analysis revealed that postoperative distant recurrence was a significant poor prognostic factor for survival after recurrence (HR=1.85, 95% CI=1.06-3.25, p=0.03), and combining ICIs with chemotherapy significantly improved survival after recurrence (HR=0.43, 95% CI=0.24-0.78, p<0.01). CONCLUSION: Combination of ICIs with chemotherapy significantly prolonged survival of postoperative recurrence with wild-type EGFR NSCLC regardless of PD-L1 status.

DOI： 10.21873/anticanres.17165

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PubMed

Transcriptomic profiling of a late recurrent nuclear protein in testis carcinoma of the lung 14 years after the initial operation: a case report Reviewed

Taketo Kato, Hironori Oyamatsu, Yuki Hanamatsu, Heng Huang, Shoji Okado, Yoshito Imamura, Yuji Nomata, Hiroki Watanabe, Yuka Kadomatsu, Harushi Ueno, Shota Nakamura, Tetsuya Mizuno, Tetsunari Hase, Tamotsu Takeuchi, Toyofumi Fengshi Chen-Yoshikawa

Translational Lung Cancer Research Vol. 13 ( 7 ) page： 1756 - 1762 2024.7

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Background: Nuclear protein in testis (NUT) carcinoma (NC) of the lung is a rare cancer that occurs mainly in young adolescents and adults. NC is genetically characterized by NUTM1 rearrangements, which usually take the form of BRD4-NUT fusions. The prognosis for NC is dismal, and treatment with conventional chemotherapeutic regimens is ineffective. Case Description: We herein describe the case of a 53-year-old woman with recurrent NC of the lung 14 years after surgery for nasal cavity cancer. Chest computed tomography revealed a 5.5-cm tumor in the lower lobe of the left lung. We completely resected the recurrent lung NC via thoracotomy. Immunohistochemistry (IHC) of the lung and nasal cavity cancers showed diffuse strong expression of NUT. RNA-seq of the lung NC revealed NUTM1 rearrangement, with a fusion of BRD4 exon 10 to NUTM1 exon 4. This breakpoint has never been reported before. In addition, IHC revealed elevated expression of parathyroid hormone-like hormone in the lung NC but not in the nasal cavity NC, indicating that the lung and nasal cavity NCs were metachronous multiple primary cancers. Conclusions: We experienced a rare recurrence of lung NC 14 years after the initial surgery. The BRD4-NUT fusion consisted of a new breakpoint. Furthermore, the expression pattern of parathyroid hormone-like hormone (PTHLH) suggested that the NCs in the nasal cavity and lung may be metachronous multiple lung cancers. This extremely rare case highlighted the possibility of identifying less malignant NCs in patients with poorly differentiated tumors via fusion gene analysis and the need to develop more effective treatment strategies for this malignancy.

DOI： 10.21037/tlcr-24-259

Scopus

Endobronchial Closure for Peripheral Pulmonary Air Leakage. Reviewed International journal

Shoji Okado, Shota Nakamura, Keiyu Sato, Harushi Ueno, Takayasu Ito, Kazuhide Sato, Shotaro Okachi, Yohei Uehara, Misa Matsumoto, Natsumi Shimazaki, Katsuya Miyagawa, Toyofumi Fengshi Chen-Yoshikawa

Respiration 2024.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: A minimally invasive alternative to surgery for treating pneumothorax has been developed, aiming to reduce risks while maintaining efficacy. This study conducted basic experiments using Ex vivo and in vivo pig lung employing a super-thin catheter for treatment. This new device injects fibrin glue directly into the responsible lesion to close the air leak, which has two features; thin design and double-lumen. METHODS: The experimental setup involved utilizing trachea and both lung specimens from pigs under positive pressure ventilation. To simulate pneumothorax, artificial fistulas were created on the lung surfaces. The super-thin catheter, guided through a bronchoscope near the fistula, was used to embolize the peripheral bronchus by injecting a fibrin preparation. Then, an air leak test was conducted afterward to assess the efficacy of the treatment. Additionally, a similar pneumothorax model was induced in alive pig under general anesthesia to evaluate its curability. RESULTS: In the extracted pig lungs, embolization was performed in 21 cases, resulting in the cessation of air leaks in 19 cases, corresponding to a 90.5% cure rate. Notably, no major adverse events occurred with the treatment devices. Similarly, in living pigs, pneumothorax was successfully treated, with no recurrence observed up to the seventh postoperative day. CONCLUSION: The novel treatment device utilizing a super-thin catheter offers a minimally invasive and highly curative option for pneumothorax. These promising results suggest the potential for further development and human clinical trials, which could revolutionize the treatment of pneumothorax, reducing risks and improving outcomes.

DOI： 10.1159/000540652

PubMed

Future directions for xenotransplantation in lungs. Invited Reviewed International journal

Hidetaka Hara, Hisashi Sahara, Toyofumi Fengshi Chen-Yoshikawa

Current opinion in organ transplantation Vol. 29 ( 5 ) page： 332 - 339 2024.7

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE OF REVIEW: Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications. RECENT FINDINGS: The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies. SUMMARY: Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.

DOI： 10.1097/MOT.0000000000001161

Scopus

PubMed

Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report. Reviewed International journal

Ayaka Makita, Shota Nakamura, Tomohiro Setogawa, Yoshito Imamura, Shoji Okado, Yuji Nomata, Hiroki Watanabe, Yuta Kawasumi, Yuka Kadomatsu, Harushi Ueno, Taketo Kato, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

Surgical case reports Vol. 10 ( 1 ) page： 170 - 170 2024.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate. CASE PRESENTATION: We report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient's age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery. CONCLUSIONS: We report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.

DOI： 10.1186/s40792-024-01970-2

PubMed

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Papers - CHEN-YOSHIKAWA Toyofumi