研究活動情報

• Evaluating the Efficacy of Thin Convex-probe Endobronchial Ultrasound Bronchoscope in Cadaveric Models.
  Yuta Takashima; Naofumi Shinagawa; Tetsuaki Shoji; Masahiro Kashima; Hitoki Arisato; Daisuke Morinaga; Tomoo Ikari; Shotaro Ito; Kosuke Tsuji; Hirofumi Takahashi; Toshiaki Shichinohe; Satoshi Konno
  Journal of bronchology & interventional pulmonology, 32, 3, 2025年07月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The convex-probe endobronchial ultrasound (CP-EBUS) bronchoscope is widely used in clinical practice. Despite improvements, the existing CP-EBUS remains limited in accessing areas beyond the mediastinum due to its large distal end diameter, long rigid tip segment, and oblique viewing angle. To address this limitation, Olympus Medical Systems Corporation developed the thin CP-EBUS (TCP-EBUS). This study aimed to compare the accessibility and puncturing ability of TCP-EBUS with existing CP-EBUS in cadaveric models. METHODS: Ten bronchoscopists conducted this study using 2 cadaveric models. The accessibility of TCP-EBUS was evaluated based on the number of bronchial generations that could be reached. To assess the puncturing ability of TCP-EBUS, needle punctures were performed on previously created simulated lesions in the segmental or subsegmental bronchial area, and puncture success rates were calculated. RESULTS: TCP-EBUS demonstrated greater accessibility than CP-EBUS in all segmental bronchi, with statistically significant differences observed in several bronchi (P<0.05). Puncture success rates for simulated lesions using TCP-EBUS were also significantly higher than those using CP-EBUS in both the segmental (85.0% vs. 60.0%, P<0.001) and subsegmental bronchial areas (84.4% vs. 38.9%, P<0.001). In a questionnaire survey, TCP-EBUS was perceived as significantly superior in terms of usability (P<0.05). CONCLUSION: TCP-EBUS has significantly improved both accessibility and puncture performance, providing an advantage over CP-EBUS in segmental and subsegmental bronchial areas. TCP-EBUS has the potential to expand the indications for endobronchial ultrasound-guided transbronchial needle aspiration.
• Midkine Promotes Tumor Growth and Attenuates the Effect of Cisplatin in Small Cell Lung Cancer.
  Shotaro Ito; Jun Sakakibara-Konishi; Mineyoshi Sato; Tetsuaki Shoji; Megumi Furuta; Hirofumi Takahashi; Kosuke Tsuji; Daisuke Morinaga; Masahiro Kashima; Hidenori Kitai; Junko Kikuchi; Eiki Kikuchi; Kanako C Hatanaka; Yutaka Hatanaka; Kyoko Hida; Takuro Noguchi; Satoshi Konno
  Cancer medicine, 14, 13, e71034, 2025年07月, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Small cell lung cancer (SCLC) is a highly aggressive disease associated with poor patient survival rates. The addition of an anti-programmed death ligand 1 antibody to platinum combination chemotherapy can improve its prognosis. However, only a few patients achieve a long-term response; thus, establishing new therapies for SCLC is crucial. Midkine (MDK) is a heparin-binding growth factor involved in various biological processes, including cell proliferation and chemotherapeutic resistance, in diverse cancers. MDK has garnered attention as a therapeutic and diagnostic target for several cancers; however, only a few studies have evaluated its expression and function in SCLC. This study aimed to evaluate the MDK expression in human SCLC tissue and human SCLC cell lines, and to clarify its function in tumorigenesis. METHODS: MDK expression was analyzed in vitro and in vivo through ELISA, immunohistochemistry, and western blotting. Its effects on cell proliferation, as well as the effects of cisplatin, were evaluated using the MTT assay. RESULTS: MDK was pathologically expressed in human SCLC tumor tissues but not in normal lung tissues. Serum MDK concentrations in patients with SCLC reflected the SCLC tumor burden and were correlated with response to treatment. Moreover, MDK induced cell proliferation and attenuated the effects of cisplatin in SCLC cell lines. An MDK inhibitor and cisplatin exerted synergistic antitumor effects both in vitro and in vivo. Furthermore, MDK positively regulated the AKT pathway. CONCLUSION: Our findings indicate that MDK promotes cell proliferation and chemotherapeutic resistance by activating the AKT pathway in SCLC cells. Therefore, MDK may be a potential therapeutic and diagnostic target for SCLC.
• Frequency and Prognostic Impact of Local Ablation Therapy for Oligoprogression in Non-Small Cell Lung Cancer.
  Daisuke Morinaga; Jun Sakakibara-Konishi; Ryohei Kamada; Masahiro Kashima; Kosuke Tsuji; Shotaro Ito; Megumi Furuta; Tetsuaki Shoji; Yuta Takashima; Hidenori Kitai; Yasuyuki Ikezawa; Hiroshi Taguchi; Tatsuya Kato; Yoshiki Shinomiya; Kanako C Hatanaka; Yutaka Hatanaka; Satoshi Konno
  Thoracic cancer, 16, 13, e70119, 2025年07月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: During the systemic treatment of patients with non-small cell lung cancer (NSCLC), oligoprogression (OP), a condition in which most lesions remain controlled while a few progress or develop, has recently attracted attention. Traditionally, systemic therapy is continued after disease progression; however, advancements in local ablation therapy (LAT), such as radiotherapy and surgery, have demonstrated clinical efficacy in patients with OP. The characteristics of patients who may benefit from LAT or their genetic background remain unclear. This study evaluated the frequency, clinicopathological characteristics, and efficacy of LAT in the treatment of OP. METHODS: A retrospective review was conducted of 510 patients with NSCLC who experienced disease progression after systemic therapy. RESULTS: Overall, 106/510 (23.6%) patients exhibited OP; among these, six patients who received only the best supportive care after OP were excluded. Systemic therapy alone was administered to 79 patients (79.0%), while 21 (21.0%) received LAT. Median local progression-free survival was numerically longer in the LAT group than in the systemic therapy-only group (8.3 and 6.7 months, respectively; p = 0.38). In addition, overall survival was also numerically longer in the LAT group than in the systemic therapy-only group (78.1 and 55.1 months, respectively; p = 0.57). Ribonucleic acid sequencing revealed an increase in extracellular matrix-related gene expression after OP, providing potential molecular insights. CONCLUSIONS: Although this study found no significant prognostic benefit of LAT in patients with OP, future research integrating clinical and molecular data may identify patients most likely to benefit from LAT.
• Evaluating the Usefulness of the Insertion Tube Rotation Function of Bronchoscope in Cadaver Models.
  Naofumi Shinagawa; Yuta Takashima; Masahiro Kashima; Daisuke Morinaga; Shotaro Ito; Kosuke Tsuji; Mineyoshi Sato; Hirofumi Takahashi; Tetsuaki Shoji; Megumi Furuta; Toshiaki Shichinohe; Satoshi Konno
  Journal of bronchology & interventional pulmonology, 32, 2, 2025年04月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The Olympus bronchoscope is equipped with an insertion tube rotation function; however, data on its usefulness are currently limited. Here, we evaluated the amount of body and wrist movement required by bronchoscopists, the operability of the bronchoscope, and its ease of use with and without the insertion tube rotation function. METHODS: This study was performed on 10 bronchoscopists using 2 cadaveric bodies. The primary endpoint was the amount of movement exerted by the bronchoscopist, which was evaluated using motion capture. We also assessed the deepest bronchial generations that could be reached by the bronchoscope and the time required for insertion. Immediately after the procedures, the bronchoscopists completed a questionnaire to evaluate their perceived difficulty level. RESULTS: The bronchoscopists achieved a 33.5% reduction in wrist rotation (67.8 vs. 110.2 degrees, P<0.05) and a 23.9% reduction in body rotation (17.2 vs. 24.4 degrees, P<0.05) using the insertion tube rotation function for all segmental bronchi. During forceps insertion to simulated lesions, the bronchoscopists' body movement was reduced by 65.1% (11.6 vs. 33.9 degrees, P<0.05), and wrist rotation by 47.6% (63.5 vs. 122.7 degrees, P<0.05). Furthermore, bronchoscopists experienced significantly reduced difficulty inserting biopsy forceps toward simulated target lesions (3.9 vs. 3.2 points, P<0.05) and required less assistance (4.0 vs. 2.0 points, P<0.05) when using the insertion tube rotation function. CONCLUSION: The insertion tube rotation function of the bronchoscope facilitated its insertion and improved operability.
• Efficacy and safety of lenvatinib in a case of thymic carcinoma complicated with interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: A case report.
  Yuki Hatakeyama; Jun Sakakibara-Konishi; Masato Tarumi; Kosuke Tsuji; Hirofumi Takahashi; Megumi Furuta; Yuta Takashima; Hidenori Kitai; Tetsuaki Shoji; Yasuyuki Ikezawa; Satoshi Konno
  Respiratory medicine case reports, 54, 102181, 102181, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, Based on the results of a multicenter phase II study of patients with previously treated thymic carcinoma, lenvatinib administration for unresectable thymic cancer has been covered under insurance in Japan since 2021. However, patients with interstitial lung disease (ILD) were excluded from that study; therefore, the efficacy and safety of lenvatinib in these patients remain unknown. Herein, we report the case of a woman in her 50s who was diagnosed with thymic carcinoma complicated with ILD. In August 2016, the patient developed ILD with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM). She received triple therapy comprising prednisolone, tacrolimus and azathioprine. In October 2021, the patient complained of lateral chest pain and back pain. In January 2022, computed tomography (CT) revealed an anterior mediastinal tumor, and percutaneous biopsy resulted in a diagnosis of thymic carcinoma with Masaoka classification IVb. In March 2022, first-line treatment with four cycles of carboplatin (area under the curve, 6) + paclitaxel (200 mg/m2) was initiated. Although a partial response was achieved, in September 2022, CT demonstrated progressive disease (PD). Therefore, in October 2022, Lenvatinib (24 mg) was started as the second-line treatment. The best response was stable disease; moreover, although lenvatinib dose reduction was required owing to adverse events, such as biliary-tract infection and stomatitis. The patient did not experience ILD exacerbation. Lenvatinib (14 mg) was continued until PD was observed in March 2023. Our findings suggest that lenvatinib is a viable treatment option for thymic carcinoma with ILD.
• Durvalumab after chemoradiotherapy in non-small cell lung cancer with EGFR mutation: A real-world study (HOT2101).
  Kosuke Tsuji; Hidenori Mizugaki; Keiki Yokoo; Maki Kobayashi; Yosuke Kawashima; Nozomu Kimura; Hiroshi Yokouchi; Hajime Kikuchi; Toshiyuki Sumi; Yasutaka Kawai; Kenta Kobashi; Ryo Morita; Kenichiro Ito; Yasuo Kitamura; Hiroyuki Minemura; Keiichi Nakamura; Mari Aso; Osamu Honjo; Hisashi Tanaka; Taichi Takashina; Kyoji Tsurumi; Jun Sugisaka; Yoko Tsukita; Satoshi Konno; Satoshi Oizumi
  Cancer science, 115, 4, 1273, 1282, 2024年04月, ［国際誌］
  英語, 研究論文（学術雑誌）, Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients.
• Extended ICI treatment after first-line chemoimmunotherapy could predict the clinical benefit of ramucirumab plus docetaxel in advanced non-small lung cancer: Post hoc analysis from NEJ051 (REACTIVE study).
  Ou Yamaguchi; Keita Mori; Saori Takata; Kazuhiko Shibata; Kenichi Chikamori; Nozomu Kimura; Yoshiaki Nagai; Taku Nakagawa; Satoshi Igawa; Taishi Harada; Hiroshige Yoshioka; Hisashi Tanaka; Hitomi Nogawa; Hiroaki Satoh; Toshihiro Shiozawa; Kosuke Tsuji; Kunihiko Kobayashi; Kyoichi Kaira
  Thoracic cancer, 15, 2, 163, 171, 2024年01月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The factors that predict the clinical response to ramucirumab plus docetaxel (RD) after first-line chemoimmunotherapy are unresolved. We explored whether the therapeutic efficacy of prior chemoimmunotherapy could predict the outcome of RD as sequential therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Our study comprised 288 patients with advanced NSCLC who received RD as the second-line treatment after first-line chemoimmunotherapy at 62 Japanese institutions. Chemoimmunotherapy consisted of a platinum-based regimen and immune checkpoint inhibitors (ICIs). The association between several variables and the therapeutic outcome of RD was determined via logistic regression analysis. RESULTS: Of the 288 patients, 225 (78.1%) received maintenance therapy and 108 (37.5%) received both ICI treatment for >180 days and maintenance therapy. All of 108 patients having ICIs for >180 days received maintenance therapy. Univariate analysis identified performance status, histology (adenocarcinoma), maintenance therapy, and ICI treatment >180 days as significant predictors of better progression-free survival (PFS) and overall survival (OS) after RD administration. Multivariate analysis confirmed that these factors independently predicted favorable PFS and OS. The therapeutic response and PD-L1 expression were not closely associated with outcome after RD treatment. In particular, maintenance therapy >4 cycles was more predictive of the better prognosis for RD treatment. CONCLUSION: Extended ICI treatment after chemoimmunotherapy and maintenance therapy enhanced the efficacy of second-line RD treatment in patients with advanced NSCLC.
• Inhibition of non-homologous end joining mitigates paclitaxel resistance resulting from mitotic slippage in non-small cell lung cancer.
  Kosuke Tsuji; Eiki Kikuchi; Yuta Takashima; Tetsuaki Shoji; Hirofumi Takahashi; Shotaro Ito; Daisuke Morinaga; Masahiro Kashima; Makie Maeda; Hidenori Kitai; Junko Kikuchi; Jun Sakakibara-Konishi; Satoshi Konno
  Cell cycle (Georgetown, Tex.), 22, 17, 1854, 1864, 2023年09月, ［国際誌］
  英語, 研究論文（学術雑誌）, Mitotic slippage, which enables cancer cells to bypass cell death by transitioning from mitosis to the G1 phase without undergoing normal cytokinesis, is one likely mechanism of paclitaxel (PTX) resistance. DNA double-strand breaks (DSBs) in the G1 phase are mainly repaired through non-homologous end joining (NHEJ). Therefore, inhibiting NHEJ could augment the PTX-induced cytotoxicity by impeding the repair of PTX-induced DSBs during the G1 phase following mitotic slippage. We aimed to evaluate the effects of NHEJ inhibition on mitotic slippage after PTX treatment in non-small cell lung cancer (NSCLC). H1299, A549, H1975, and H520 NSCLC cell lines were employed. In addition, A-196 and JQ1 were used as NHEJ inhibitors. H1299 cells were PTX-resistant and exhibited an increased frequency of mitotic slippage upon PTX treatment. NHEJ inhibitors significantly augmented the PTX-induced cytotoxicity, DSBs, and apoptosis in H1299 cells. The newly generated PTX-resistant cells were even more prone to mitotic slippage following PTX treatment and susceptible to the combined therapy. Docetaxel further demonstrated synergistic effects with the NHEJ inhibitor in PTX-resistant cells. NHEJ inhibition may overcome intrinsic or acquired PTX resistance resulting from mitotic slippage by synergistically increasing the cytotoxic effects of antimitotic drugs in NSCLC.
• Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer.
  Hirofumi Takahashi; Jun Sakakibara-Konishi; Megumi Furuta; Tetsuaki Shoji; Kosuke Tsuji; Daisuke Morinaga; Eiki Kikuchi; Junko Kikuchi; Takuro Noguchi; Kanako C Hatanaka; Yutaka Hatanaka; Naofumi Shinagawa; Satoshi Konno
  Cancer science, 114, 4, 1635, 1650, 2023年04月, ［国際誌］
  英語, 研究論文（学術雑誌）, Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has shown marked antitumor activity in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, these effects are transient and most patients develop resistance. Reversible drug-tolerant persister (DTP) cells are defined as a small subpopulation of cells with markedly reduced sensitivity and non-genetic acquired resistance to EGFR-TKIs. Notch is a transmembrane receptor that plays an important role in tumorigenesis. We previously reported that there is significant crosstalk between the Notch and EGFR pathways in NSCLC. Moreover, the Notch pathway is associated with resistance to previous-generation EGFR-TKIs. However, the role of Notch in osimertinib resistance is not fully understood. In this study, we evaluated whether Notch is involved in osimertinib resistance. We show that NOTCH1 and Notch target genes are upregulated in osimertinib DTP cells, and that the addition of a γ-secretase inhibitor (GSI), a Notch inhibitor, impairs drug-tolerant persistence in vitro and in vivo. Compared with osimertinib, combined GSI and osimertinib suppress phospho-ERK partly by enhancing DUSP1 expression. Furthermore, Notch1 and HES1 were upregulated after EGFR-TKI treatment in half of human EGFR-mutated NSCLC tumor tissues. These results suggest that the combination of GSI and osimertinib may be a potential therapy for EGFR-mutated NSCLC.
• Proposal of COVID-19 Clinical Risk Score for the management of suspected COVID-19 cases: a case control study.
  Sho Nakakubo; Masaru Suzuki; Keisuke Kamada; Yu Yamashita; Junichi Nakamura; Hiroshi Horii; Kazuki Sato; Munehiro Matsumoto; Yuki Abe; Kosuke Tsuji; Nobuhisa Ishiguro; Yasuyuki Nasuhara; Satoshi Konno
  BMC infectious diseases, 20, 1, 858, 858, 2020年11月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: No clinical scoring system has yet been established to estimate the likelihood of coronavirus disease (COVID-19) and determine the suitability of diagnostic testing in suspected COVID-19 patients. METHODS: This was a single-center, retrospective, observational study of patients with suspected COVID-19 and confirmed COVID-19. Patient background, clinical course, laboratory and computed tomography (CT) findings, and the presence of alternative diagnoses were evaluated. Clinical risk scores were developed based on clinical differences between patients with and without COVID-19. RESULTS: Among 110 patients suspected of having COVID-19, 60.9% underwent polymerase chain reaction (PCR) testing based on the judgment of physicians. Two patients were found to have COVID-19. The clinical characteristics of 108 non-COVID-19 patients were compared with those of 23 confirmed COVID-19 patients. Patients with COVID-19 were more likely to have a history of high-risk exposures and an abnormal sense of taste and smell. The COVID-19 group had significantly higher rates of subnormal white blood cell counts, lower eosinophil counts, and lower procalcitonin levels than the non-COVID-19 group. When blood test results, CT findings, and the presence of alternative diagnoses were scored on an 11-point scale (i.e., "COVID-19 Clinical Risk Score"), the COVID-19 group scored significantly higher than the non-COVID-19 group, more than four points in the COVID-19 group. All non-COVID patients who did not undergo PCR had a score of 4 or less. CONCLUSIONS: The COVID-19 Clinical Risk Score may enable the risk classification of patients suspected of having COVID-19 and can help in decision-making in clinical practice, including appropriateness of diagnostic testing. Further studies and prospective validation with an increased sample size are required.
• Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer.
  Tetsuaki Shoji; Eiki Kikuchi; Junko Kikuchi; Yuta Takashima; Megumi Furuta; Hirofumi Takahashi; Kosuke Tsuji; Makie Maeda; Ichiro Kinoshita; Hirotoshi Dosaka-Akita; Jun Sakakibara-Konishi; Satoshi Konno
  Cancer chemotherapy and pharmacology, 85, 5, 843, 853, 2020年05月, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: We evaluated the expression of proteasome subunits to assess whether the proteasome could be a therapeutic target in cisplatin-resistant lung cancer cells. METHODS: Cisplatin-resistant (CR) variants were established from three non-small cell lung cancer (NSCLC) cell lines (A549, H1299, and H1975) and two small cell lung cancer (SCLC) cell lines (SBC3 and SBC5). The expression of proteasome subunits, the sensitivity to immunoproteasome inhibitors, and 20S proteasomal proteolytic activity were examined in the CR variants of the lung cancer cell lines. RESULTS: All five CR cell lines highly expressed one or both of the immunoproteasome subunit genes, PSMB8 and PSMB9, while no clear trend was observed in the expression of constitutive proteasome subunits. The CR cells expressed significantly higher levels of PSMB8 and PSMB9 proteins, as well. The CR variants of the H1299 and SBC3 cell lines were more sensitive to immunoproteasome inhibitors, and had significantly more proteasomal proteolytic activity than their parental counterparts. CONCLUSIONS: The immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC.
• Lung metastasis from gastric cancer presenting as diffuse ground-glass opacities.
  Yuki Abe; Masaru Suzuki; Kosuke Tsuji; Mineyoshi Sato; Hirokazu Kimura; Hiroki Kimura; Kentaro Nagaoka; Emi Takakuwa; Yoshihiro Matsuno; Satoshi Konno
  Respiratory medicine case reports, 30, 101104, 101104, 2020年, ［国際誌］
  英語, 研究論文（学術雑誌）, Most metastatic lung tumors display well-defined, round, multiple nodular shadows, whereas the presence of diffuse ground-glass opacities on chest computed tomography generally suggests non-malignant conditions. Here, we report an unusual case of pulmonary metastasis from gastric cancer in which diffuse ground-glass opacities were observed in all lung segments. A 59-year-old man with a 3-month history of worsening chest pain and shortness of breath was referred to the pulmonary clinic. Chest computed tomography revealed low attenuation areas, suggesting emphysema, along with diffuse ground-glass opacities and interlobular septal thickening in both lungs. A transbronchial lung biopsy specimen revealed signet-ring cell carcinoma infiltrating the alveolar septa. Immunohistochemical staining of the cancer cells was positive for CDX-2, cytokeratin 7, and cytokeratin 20, and negative for surfactant apoprotein-A, TTF-1, and Napsin A. Gastrointestinal endoscopy revealed an ulcerative tumor in the stomach, and a biopsy from the tumor demonstrated malignant cells with similar morphology and immunophenotypes as those in the lungs. The final diagnosis was diffuse lung metastasis from gastric cancer. Our case shows that although multiple, well-defined nodules are typically considered to be the classic presentation of pulmonary metastasis, clinicians should also be aware of the possibility of pulmonary metastasis presenting as diffuse ground-glass opacities.