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4. Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Author

Shi, Jianxin, Shiraishi, Kouya, Choi, Jiyeon, Matsuo, Keitaro, Chen, Tzu-Yu, Dai, Juncheng, Hung, Rayjean J, Chen, Kexin, Shu, Xiao-Ou, Kim, Young Tae, Landi, Maria Teresa, Lin, Dongxin, Zheng, Wei, Yin, Zhihua, Zhou, Baosen, Song, Bao, Wang, Jiucun, Seow, Wei Jie, Song, Lei, Chang, I-Shou, Hu, Wei, Chien, Li-Hsin, Cai, Qiuyin, Hong, Yun-Chul, Kim, Hee Nam, Wu, Yi-Long, Wong, Maria Pik, Richardson, Brian Douglas, Funderburk, Karen M, Li, Shilan, Zhang, Tongwu, Breeze, Charles, Wang, Zhaoming, Blechter, Batel, Bassig, Bryan A, Kim, Jin Hee, Albanes, Demetrius, Wong, Jason YY, Shin, Min-Ho, Chung, Lap Ping, Yang, Yang, An, She-Juan, Zheng, Hong, Yatabe, Yasushi, Zhang, Xu-Chao, Kim, Young-Chul, Caporaso, Neil E, Chang, Jiang, Ho, James Chung Man, Kubo, Michiaki, Daigo, Yataro, Song, Minsun, Momozawa, Yukihide, Kamatani, Yoichiro, Kobayashi, Masashi, Okubo, Kenichi, Honda, Takayuki, Hosgood, Dean H, Kunitoh, Hideo, Patel, Harsh, Watanabe, Shun-ichi, Miyagi, Yohei, Nakayama, Haruhiko, Matsumoto, Shingo, Horinouchi, Hidehito, Tsuboi, Masahiro, Hamamoto, Ryuji, Goto, Koichi, Ohe, Yuichiro, Takahashi, Atsushi, Goto, Akiteru, Minamiya, Yoshihiro, Hara, Megumi, Nishida, Yuichiro, Takeuchi, Kenji, Wakai, Kenji, Matsuda, Koichi, Murakami, Yoshinori, Shimizu, Kimihiro, Suzuki, Hiroyuki, Saito, Motonobu, Ohtaki, Yoichi, Tanaka, Kazumi, Wu, Tangchun, Wei, Fusheng, Dai, Hongji, Machiela, Mitchell J, Su, Jian, Kim, Yeul Hong, Oh, In-Jae, Lee, Victor Ho Fun, Chang, Gee-Chen, Tsai, Ying-Huang, Chen, Kuan-Yu, Huang, Ming-Shyan, Su, Wu-Chou, Chen, Yuh-Min, Seow, Adeline, Park, Jae Yong, and Kweon, Sun-Seog

Subjects
Genetics, Cancer, Clinical Research, Human Genome, Prevention, Lung, Lung Cancer, Tobacco, Tobacco Smoke and Health, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Adenocarcinoma of Lung, Asia, Eastern, Lung Neoplasms, Polymorphism, Single Nucleotide
Abstract

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Published
2023

13. Epithelial granuloma occurring on the staple‐stump after segmentectomy for ovarian cancer lung metastasis.

Author

Kuriyama, Shoji, Imai, Kazuhiro, Nanjo, Hiroshi, Takashima, Shinogu, Iwai, Hidenobu, Demura, Ryo, Suzuki, Haruka, Harata, Yuzu, Shibano, Sumire, and Minamiya, Yoshihiro

Subjects
BIOPSY, STAPLERS (Surgery), RADIOPHARMACEUTICALS, GRANULOMA, CANCER relapse, OVARIAN tumors, DEOXY sugars, COMPUTED tomography, POSITRON emission tomography computed tomography, TUMOR markers, DIAGNOSTIC errors, FOREIGN bodies, METASTASIS, SURGICAL complications, LUNG tumors
Abstract

When a mass occurs at the staple line following lung resection, it can be difficult to distinguish between local cancer recurrence and granuloma. We present a case of a staple‐line granuloma with 18F‐fluorodeoxyglucose‐positron emission tomography uptake and elevated serum carbohydrate antigen 19–9 (CA19‐9) in a patient with ovarian cancer lung metastasis. After granuloma resection, serum CA19‐9 levels normalized, and CA19‐9 positive cells were identified in the resected tumor. Therefore, serum CA19‐9 elevation does not rule out a staple‐line granuloma. Whereas granulomas on computed tomography (CT) scans tend to show smooth shadows along the staple line unilaterally, detailed CT evaluation may help diagnostic differentiation. Differentiation based on imaging and tumor markers has limitations. However, core needle biopsy has the risk of misdiagnosis and tumor cell dissemination, therefore surgical resection should be considered when comprehensive findings indicate a potential recurrence. [ABSTRACT FROM AUTHOR]

Published
2024
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26. A Prospective Cohort Study Assessing the Relationship between Plasma Levels of Osimertinib and Treatment Efficacy and Safety

Author

Fukuhara, Tatsuro, primary, Imai, Kazuhiro, additional, Nakagawa, Taku, additional, Igusa, Ryotaro, additional, Yokota, Hayato, additional, Watanabe, Kana, additional, Suzuki, Aya, additional, Morita, Mami, additional, Onodera, Ren, additional, Inoue, Akira, additional, Miura, Masatomo, additional, Minamiya, Yoshihiro, additional, and Maemondo, Makoto, additional

Published
2023
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27. Impact of the COVID‐19 pandemic on the primary lung cancer screening program in Akita Prefecture, a region with the fastest aging population in Japan

Author

Okuda, Yuji, primary, Sato, Kazuhiro, additional, Asano, Mariko, additional, Kudoh, Kentaroh, additional, Omoto, Eiki, additional, Izumiya, Yuka, additional, Sakamoto, Sho, additional, Takeda, Masahide, additional, Shimizu, Tatsunori, additional, Ota, Hidetaka, additional, Kurokawa, Hirokazu, additional, Minamiya, Yoshihiro, additional, and Nakayama, Katsutoshi, additional

Published
2023
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31. High TLR6 Expression Status Predicts a More Favorable Prognosis after Esophagectomy for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Author

Sato, Yusuke, primary, Wakita, Akiyuki, additional, Maeda, Eri, additional, Nagaki, Yushi, additional, Sasamori, Ryohei, additional, Kemuriyama, Kohei, additional, Nozaki, Shu, additional, Ito, Satoru, additional, Terata, Kaori, additional, Imai, Kazuhiro, additional, Nanjo, Hiroshi, additional, Nomura, Kyoko, additional, and Minamiya, Yoshihiro, additional

Published
2023
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35. Preoperative neoadjuvant chemoradiotherapy provides borderline resectable thoracic esophageal cancer with equivalent treatment results as clinically T3 thoracic esophageal cancer.

Author

Wakita, Akiyuki, Motoyama, Satoru, Sato, Yusuke, Nagaki, Yushi, Fujita, Hiromu, Kemuriyama, Kohei, Hayashi, Kenjiro, Imai, Kazuhiro, Nanjo, Hiroshi, and Minamiya, Yoshihiro

Abstract

Aim: Because the optimal treatment strategy for borderline resectable (cT3br) thoracic esophageal cancer patients remains unclear, it is of great interest whether preoperative neoadjuvant therapy for cT3br could achieve results comparable to those seen with resectable T3 cancer (cT3r). We speculated that preoperative neoadjuvant chemoradiotherapy (NACRT) would be particularly effective in cT3br thoracic esophageal cancer patients and compared to cT3br and cT3r. Methods: Of 186 cT3 thoracic esophageal cancer patients treated with intended NACRT, 162 received radical esophagectomy. More than 97% were squamous cell carcinomas. Patients were partitioned into two groups according to whether invasion of adjacent organs was suspected (cT3br and cT3r). Treatment outcomes and survival were analyzed. Results: Sixty‐eight patients (36.6%) were classified as cT3br and 118 (63.4%) as cT3r. The cT3br group had significantly more tumors in the upper and middle mediastinum (p < 0.0001) and more cases with cM1 (lymph node) (p = 0.0104) than the cT3r group. In addition, the cT3br patients receiving esophagectomy exhibited a significantly lower pathological complete response rate than the cT3r patients (p = 0.0374). However, the R0 resection rate did not differ between the cT3br and cT3r patients (p = 0.0978), and the two groups treated with intended NACRT had similar 5‐year overall (OS) and disease‐specific survival (DSS) (p = 0.3831 and p = 0.9020). In addition, the incidence and patterns of recurrence did not differ between the cT3br and cT3r patients receiving esophagectomy (p = 0.8109 and p = 0.3128). Conclusions: Preoperative neoadjuvant chemoradiotherapy appears to be a promising treatment for patients with borderline resectable thoracic esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Published
2023
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37. A Retrospective Cohort Study Comparing Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Patients with Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Author

Sato, Yusuke, Motoyama, Satoru, Maeda, Eri, Wada, Yuki, Wakita, Akiyuki, Nagaki, Yushi, Fujita, Hiromu, Kemuriyama, Kohei, Hayashi, Kenjiro, Nomura, Kyoko, and Minamiya, Yoshihiro

Subjects
neoadjuvant treatment, esophagectomy, prognosis, esophageal squamous cell carcinoma, chemoradiotherapy
Abstract

Background : Based on results from the Japan Clinical Oncology Group (JCOG) 9204 and JCOG 9907 trials, neoadjuvant-CF (cisplatin+5-fluorouracil) followed by esophagectomy with extended lymphadenectomy is the standard treatment for patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) in Japan. Recently, however, results from the JCOG 1109 trial revealed that neoadjuvant-DCF (docetaxel+cisplatin+5-fluorouracil) provides significantly better overall survival (OS) than neoadjuvant-CF, whereas neoadjuvant chemoradiotherapy (NACRT) did not produce significantly better outcomes than neoadjuvant-CF.Methods : We retrospectively identified 225 ESCC patients treated between December 2008 and December 2021 who received esophagectomy at Akita University Hospital. These patients were divided into neoadjuvant-CF (NAC, n=30) and NACRT (NACRT, n=195) groups before esophagectomy. Using the Kaplan-Meier method, we compared OS and disease-specific survival (DSS) between the two groups.Results : The pathological response to treatment was significantly better in the NACRT than the NAC group. Although 5-year OS and DSS were better in the NACRT than NAC group, these differences did not reach statistical significance.Conclusion : Among patients with locally advanced thoracic ESCC, NACRT produced a significantly better pathological response than NAC. However, NACRT did not produce significantly better long-term survival than NAC, which is consistent with the results of JCOG 1109.

Published
2022

40. Pulmonary Artery Intimal Sarcoma in a Patient with Lynch Syndrome: Response to an Immune Checkpoint Inhibitor

Author

Mounai, Yue, primary, Yoshida, Taichi, additional, Ito, Shogo, additional, Fukuda, Koji, additional, Shimazu, Kazuhiro, additional, Taguchi, Daiki, additional, Shinozaki, Hanae, additional, Takagi, Daichi, additional, Imai, Kazuhiro, additional, Yamamoto, Hiroshi, additional, Minamiya, Yoshihiro, additional, Nanjyo, Hiroshi, additional, and Shibata, Hiroyuki, additional

Published
2023
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43. Squamous cell carcinoma‐derived G‐CSF promotes tumor growth and metastasis in mice through neutrophil recruitment and tumor cell proliferation, associated with poor prognosis of the patients.

Author

Kemuriyama, Kohei, An, Jianbo, Motoyama, Satoru, Nagaki, Yushi, Yamaguchi, Tomokazu, Sato, Yusuke, Wakita, Akiyuki, Minamiya, Yoshihiro, and Kuba, Keiji

Subjects
TUMOR growth, METASTASIS, CELL proliferation, PROGNOSIS, NEUTROPHILS
Abstract

Tumor‐derived G‐CSF is a well‐known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G‐CSF in squamous cell carcinoma (SCC). High expression of G‐CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR‐S1M cells produce considerable amount of G‐CSF, which expression is correlated with its metastatic potentials. Deletion of G‐CSF in NR‐S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR‐S1M tumors in the mice. Mechanistically, G‐CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR‐S1M tumor‐bearing mice, accumulation of plasma G‐CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8+ T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G‐CSF produced by NR‐S1M cells facilitates tumor progression in mice through bi‐functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G‐CSF expression. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Changes in Serum Trace Element Concentrations Before and After Surgery in Resectable Breast Cancer

Author

TAKAHASHI, ERIKO, primary, IMAI, KAZUHIRO, additional, FUKUYAMA, MAYUKO, additional, TERATA, KAORI, additional, NANJO, HIROSHI, additional, ISHIYAMA, KOICHI, additional, HIROSHIMA, YUKO, additional, YATSUYANAGI, MISAKO, additional, KUDO, CHIAKI, additional, MORISHITA, AOI, additional, WAKITA, AKIYUKI, additional, TAKASHIMA, SHINOGU, additional, SATO, YUSUKE, additional, NOMURA, KYOKO, additional, and MINAMIYA, YOSHIHIRO, additional

Published
2022
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49. Clinical implications of antegrade diastolic pulmonary artery flow in adults

Author

Fujita, Hiromu, Motoyama, Satoru, An, Jianbo, Nagakai, Yushi, Yamaguchi, Tomokazu, Koyota, Souichi, Sato, Yusuke, Wakita, Akiyuki, Imai, Kazuhiro, Kuba, Keiji, and Minamiya, Yoshihiro

Subjects
Adult, medicine.medical_specialty, Pulmonary valve, medicine.medical_treatment, Ventricular Dysfunction, Right, Diastole, Heart failure, Pulmonary Artery, medicine.artery, Internal medicine, medicine, Humans, Right ventricular dysfunction, Child, business.industry, Mortality rate, medicine.disease, medicine.anatomical_structure, Blood pressure, Echocardiography, Ventricular assist device, Pulmonary artery, Cardiology, Ventricular Function, Right, Population study, Cardiology and Cardiovascular Medicine, business
Abstract

BACKGROUND End-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PURPOSE To clarify the clinical implications of ADPAF in adults. METHODS AND RESULTS The study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSE

Published
2021

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