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6. Parathyroid Hormone-Related Protein-Producing Adenocarcinoma Suspicious of Lung Cancer: A Case Report.

Author

Hirabayashi, Masahiro, Koizumi, Tomonobu, Nakajima, Daichi, Azegami, Shuko, Midorikawa, Hajime, Kitagawa, Nami, Hamano, Hideaki, Chino, Tatsunori, and Ohya, Maki

Subjects
*PARATHYROID hormone-related protein, *CARCINOEMBRYONIC antigen, *COMPUTED tomography, *LUNG cancer, *GENETIC transcription
Abstract

Introduction: Lung adenocarcinoma with parathyroid hormone (PTH)-related hypercalcemia is uncommon. Case Presentation: A 69-year-old man was admitted to our hospital due to anorexia and fatigue. Serum calcium (15.0 mg/dL) and carcinoembryonic antigen (361.7 ng/mL) were extremely high, and PTH-related protein (PTH-rP) also elevated (16.7 pmol/L). Systemic computed tomography revealed multiple enlarged lymph nodes and disseminated peritoneal nodules, with irregularly shaped nodules in the upper lobe in the left lung. Ultrasound-guided biopsy from the axillary lymph node revealed adenocarcinoma. Immunohistological staining showed the tumor cells to be positive for cytokeratin 7 and PTH-rP and negative for cytokeratin 20 and thyroid transcription factor-1. Although the primary origin remains undetermined despite detailed examinations, possible primary tumor was considered to be lung adenocarcinoma in the present case. The serum calcium level was reduced by denosumab, but the patient died 20 days after admission. Conclusion: The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Salivary cytokine panel indicative of non-small cell lung cancer

Author

Koizumi, Tomonobu, Shetty, Vivek, and Yamaguchi, Masaki

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Dental/Oral and Craniofacial Disease, Clinical Research, Cancer, Lung Cancer, Lung, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Case-Control Studies, Cytokines, Early Detection of Cancer, Female, Humans, Lung Neoplasms, Male, Middle Aged, Saliva, Cytokine, saliva, non-small cell lung cancer, logistic regression analysis, oral mucosal transudate, combinatorial panel, multiplex analysis, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC.

Published
2018

9. Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study)

Author

Araki, Taisuke, primary, Kanda, Shintaro, additional, Komatsu, Masamichi, additional, Sonehara, Kei, additional, Tateishi, Kazunari, additional, Takada, Munetake, additional, Kato, Akane, additional, Yamamoto, Manabu, additional, Nishie, Kenichi, additional, Hama, Mineyuki, additional, Agatsuma, Toshihiko, additional, Kakizaki, Yumiko, additional, Yoshiike, Fumiaki, additional, Matsuo, Akemi, additional, Chiaki, Tomoshige, additional, Samizo, Kanae, additional, Takagi, Yoshiko, additional, Yamaura, Maki, additional, Hanaoka, Masayuki, additional, and Koizumi, Tomonobu, additional

Published
2023
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13. EGFR inhibition in EGFR ‐mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment

Author

Shiiya, Akihiko, primary, Noguchi, Takuro, additional, Tomaru, Utano, additional, Ariga, Shin, additional, Takashima, Yuta, additional, Ohhara, Yoshihito, additional, Taguchi, Jun, additional, Takeuchi, Satoshi, additional, Shimizu, Yasushi, additional, Kinoshita, Ichiro, additional, Koizumi, Tomonobu, additional, Matsuno, Yoshihiro, additional, Shinagawa, Naofumi, additional, Sakakibara‐Konishi, Jun, additional, and Dosaka‐Akita, Hirotoshi, additional

Published
2022
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16. Successful resection after first‐line lenvatinib therapy in an advanced thymic carcinoma.

Author

Shimura, Masatoshi, Miura, Kentaro, Koizumi, Tomonobu, Kanda, Shintaro, Mishima, Shuji, Hara, Daisuke, Matsuoka, Shunichiro, Eguchi, Takashi, Hamanaka, Kazutoshi, Uehara, Takeshi, and Shimizu, Kimihiro

Subjects
THERAPEUTIC use of antineoplastic agents, THYMOMA, PROTEIN kinase inhibitors, PERICARDIAL effusion, METASTASIS, TREATMENT effectiveness, MEDIASTINAL tumors, SALVAGE therapy, PROGRESSION-free survival
Abstract

Thymic carcinoma is a highly malignant tumor and treatment options are limited. Lenvatinib, a novel multitargeted kinase inhibitor, has recently been approved for the treatment of unresectable thymic carcinoma. There are no reports of complete surgical resection after the administration of first‐line lenvatinib in advanced thymic carcinoma. A 50‐year‐old man visited our hospital because a computed tomography (CT) scan of the chest showed a large thymic squamous cell carcinoma. We suspected malignant pericardial effusion, invasion of the left upper lobe of the lung, and left mediastinal lymph node metastases. The patient was diagnosed with WHO classification stage IVb disease. Lenvatinib therapy was started at 24 mg/day as first‐line therapy. Gradual dose reduction to 16 mg/day was required because of hypertension, diarrhea, and palmar‐plantar erythrodysesthesia syndrome as side effects. Chest CT findings after 6 months of lenvatinib therapy showed reduction of the main tumor, disappearance of the mediastinal lymph node metastases, and pericardial effusion. Complete salvage resection was successfully performed a month after discontinuation of lenvatinib. The patient has been disease‐free for 1 year without adjuvant therapy. Lenvatinib therapy is one of the promising therapeutic options for thymic carcinoma and may make salvage surgery increasingly useful for advanced thymic carcinoma. [ABSTRACT FROM AUTHOR]

Published
2023
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17. A case of mediastinal mesenchymal tumor with pericytic neoplasm feature that responded to radiation therapy.

Author

Muramoto, Miho, Kanda, Shintaro, Kobayashi, Takashi, Tamada, Hisashi, Fukazawa, Ayumu, Koiwai, Keiichirou, and Koizumi, Tomonobu

Subjects
BIOPSY, DIGESTIVE system endoscopic surgery, MEDIASTINAL tumors, SOFT tissue tumors, TREATMENT effectiveness, RESPIRATORY obstructions, CHEST pain, COMPUTED tomography, VIDEO-assisted thoracic surgery, SYMPTOMS
Abstract

Here, we report a case of mediastinal mesenchymal tumor with a pericytic neoplasm feature that responded to radiation therapy. A 43‐year‐old man visited our hospital with a complaint of esophageal obstruction and chest pain. Chest computed tomography revealed a middle mediastinal tumor and a mesenchymal tumor was diagnosed with a pericytic neoplasm feature by video‐assisted thoracoscopic biopsy. The definitive treatment for soft tissue tumor is surgical resection; however, the mediastinal tumor was unresectable because of esophageal and tracheal invasion. Radiation therapy was administered and there was a partial tumor response and 2 years disease‐free status. With a review of the literature, we discuss the clinical and pathological characteristics of this rare tumor and its treatment. [ABSTRACT FROM AUTHOR]

Published
2023
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18. EGFR inhibition in EGFR‐mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment.

Author

Shiiya, Akihiko, Noguchi, Takuro, Tomaru, Utano, Ariga, Shin, Takashima, Yuta, Ohhara, Yoshihito, Taguchi, Jun, Takeuchi, Satoshi, Shimizu, Yasushi, Kinoshita, Ichiro, Koizumi, Tomonobu, Matsuno, Yoshihiro, Shinagawa, Naofumi, Sakakibara‐Konishi, Jun, and Dosaka‐Akita, Hirotoshi

Abstract

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR‐mutant non–small‐cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR‐mutant cells. Using EGFR‐mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR‐TKI treatment, we found that EGFR‐mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first‐generation EGFR‐TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre‐treatment samples. Monocyte‐derived macrophages facilitated antibody‐dependent cellular phagocytosis when EGFR‐TKI‐treated EGFR‐mutant cells were incubated with anti‐CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR‐mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell‐free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP‐1 monocytes in a stimulator of interferon genes‐dependent manner. Our study indicates that EGFR inhibition in EGFR‐mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR‐mutant NSCLC. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Predictive value of post‐treatment C‐reactive protein‐to‐albumin ratio in locally advanced non–small cell lung cancer patients receiving durvalumab after chemoradiotherapy

Author

Araki, Taisuke, primary, Tateishi, Kazunari, additional, Komatsu, Masamichi, additional, Sonehara, Kei, additional, Wasamoto, Satoshi, additional, Koyama, Shigeru, additional, Yoshiike, Fumiaki, additional, Hama, Mineyuki, additional, Nishie, Kenichi, additional, Kondo, Daichi, additional, Agatsuma, Toshihiko, additional, Kato, Akane, additional, Takata, Munetake, additional, Kanda, Shintaro, additional, Hanaoka, Masayuki, additional, and Koizumi, Tomonobu, additional

Published
2022
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24. Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study

Author

Mimori, Tomoyasu, primary, Shukuya, Takehito, additional, Ko, Ryo, additional, Okuma, Yusuke, additional, Koizumi, Tomonobu, additional, Imai, Hisao, additional, Takiguchi, Yuichi, additional, Miyauchi, Eisaku, additional, Kagamu, Hiroshi, additional, Sugiyama, Tomohide, additional, Azuma, Keisuke, additional, Namba, Yukiko, additional, Yamasaki, Masahiro, additional, Tanaka, Hisashi, additional, Takashima, Yuta, additional, Soda, Sayo, additional, Ishimoto, Osamu, additional, Koyama, Nobuyuki, additional, Kobayashi, Kunihiko, additional, and Takahashi, Kazuhisa, additional

Published
2022
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32. Development of angiosarcoma in a mediastinal non‐seminomatous germ cell tumor that exhibited growing teratoma syndrome during chemotherapy

Author

Matsuoka, Shunichiro, Koyama, Tsutomu, Takeda, Tetsu, Yamada, Kyoko, Hyogotani, Akira, Hamanaka, Kazutoshi, Sekiguchi, Nodoka, and Koizumi, Tomonobu

Subjects
sarcoma, Case Report, germ cell tumor, somatic type, Case Reports, BEP chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, neoplasms, lcsh:RC254-282
Abstract

Herein, we report a case of an angiosarcoma in a mediastinal non‐seminomatous germ cell tumor that exhibited growing teratoma syndrome during chemotherapy. A 26‐year‐old man presented with a giant anterior mediastinal mass, which was diagnosed as a non‐seminomatous germ cell tumor. The patient was administered three cycles of chemotherapy (bleomycin, etoposide, and cisplatin), but the mass grew despite normalization of tumor markers. Massive bleeding during thoracic surgery resulted in incomplete resection, and the mass was clinically and pathologically diagnosed as growing teratoma syndrome (only mature teratoma). The residual mass continued to grow, and complete resection was subsequently achieved after a detailed analysis of its vascular anatomy using angiography. The final pathological findings revealed angiosarcoma, which indicated a rare somatic type of mediastinal non‐seminomatous germ cell tumor.

Published
2019

33. Primary mediastinal dedifferentiated liposarcoma: Five case reports and a review

Author

Miura, Kentaro, Hamanaka, Kazutoshi, Matsuoka, Shunichiro, Takeda, Tetsu, Agatsuma, Hiroyuki, Hyogotani, Akira, Ito, Ken‐ichi, Nishimaki, Fumihiro, Koizumi, Tomonobu, and Uehara, Takeshi

Subjects
Aged, 80 and over, Male, Biopsy, Original Articles, Liposarcoma, Middle Aged, mediastinum, Immunohistochemistry, Mediastinal Neoplasms, Tumor Burden, Dedifferentiated liposarcoma, Positron Emission Tomography Computed Tomography, Biomarkers, Tumor, Humans, Original Article, Female, local recurrence, Neoplasm Grading, Tomography, X-Ray Computed, Aged
Abstract

Background Liposarcoma has been subclassified histologically into well‐differentiated, myxoid, pleomorphic, and dedifferentiated types. The dedifferentiated type generally shows poorer prognosis than the well‐differentiated type. Because of its rarity, the clinicopathological features and clinical outcomes of primary mediastinal dedifferentiated liposarcoma remain unclear. Methods Five patients with primary mediastinal dedifferentiated liposarcoma were treated at Shinshu University Hospital between January 2012 and August 2017. We investigated the clinical characteristics, including age, gender, radiographic findings, pathological status, and clinical and treatment outcomes. Results Four of the five patients initially underwent radical surgical resection. One patient was disease‐free after surgery, but the remaining three patients developed local recurrence in the mediastinum after surgical resection. Two of these patients underwent repeat surgical resection, resulting in long survival (60 and 40 months, respectively), while the other underwent proton beam therapy and showed no evidence of recurrence as of 17 months after treatment. The remaining patient was treated with chemotherapy using doxorubicin because of advanced inoperable disease, but failed to show a response and died within a month of the initiation of chemotherapy. Although the maximum standardized uptake values on fluorodeoxyglucose‐computed tomography were relatively low, there was a slight positive relation between these values and the Ki‐67‐positive ratio in the tumor. Conclusion Aggressive treatment by surgical resection should be considered for mediastinal dedifferentiated liposarcoma, even in cases with local recurrence.

Published
2018

37. CCR4-positive peripheral T-cell lymphoma presenting as eosinophilic pneumonia and developing from prolonged pustular psoriasis

Author

Sekiguchi, Nodoka, primary, Komatsu, Masamichi, additional, Ichiyama, Takashi, additional, Kobayashi, Aya, additional, Gomi, Daisuke, additional, Fukushima, Toshirou, additional, Kobayashi, Takashi, additional, Noguchi, Takuro, additional, Nakazawa, Hideyuki, additional, Asano, Naoko, additional, Ishida, Fumihiro, additional, and Koizumi, Tomonobu, additional

Published
2021
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47. Twenty-year Follow-up of the First Bilateral Living-donor Lobar Lung Transplantation in Japan

Author

Komatsu, Masamichi, primary, Yamamoto, Hiroshi, additional, Shomura, Toshitaka, additional, Sonehara, Kei, additional, Ichiyama, Takashi, additional, Urushihata, Kazuhisa, additional, Ushiki, Atsuhito, additional, Yasuo, Masanori, additional, Wakamatsu, Toshihide, additional, Sugimoto, Seiichiro, additional, Oto, Takahiro, additional, Date, Hiroshi, additional, Koizumi, Tomonobu, additional, Hanaoka, Masayuki, additional, and Kubo, Keishi, additional

Published
2019
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49. Successful treatment with doxorubicin and ifosfamide for mediastinal malignant peripheral nerve sheath tumor with loss of H3K27me3 expression

Author

Seno, Noriko, Fukushima, Toshirou, Gomi, Daisuke, Kobayashi, Takashi, Sekiguchi, Nodoka, Matsushita, Hidehiro, Ozawa, Takesumi, Tsukahara, Yoshiko, Mamiya, Keiko, Koizumi, Tomonobu, and Sano, Kenji

Subjects
ifosfamide, mediastinal tumor, Chemotherapy, Case Report, Case Reports, doxorubicin
Abstract

Malignant peripheral nerve sheath tumor (MPNST) in the thorax is an extremely rare disease, and half of all cases of MPNST are associated with neurofibromatosis type I. Sporadic intrathoracic MPNST is difficult to diagnose and treat. Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. Herein, we present a case of inoperable mediastinal MPNST, in which the diagnosis was immunohistochemically made by the loss of H3K27me3 expression in a transbronchial needle biopsy specimen. The patient showed a good response to doxorubicin plus ifosfamide chemotherapy. The present case highlights that MPNST should be included in the differential diagnosis of non‐posterior mediastinum thoracic lesions, and that appropriate diagnosis and treatment for intrathoracic MPNST should be considered in patients with a thoracic mass.

Published
2017

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