| 1. |
Ogihara Kumi, Isomoto Hajime, Ishii Hiroyuki, Minami Hitomi, Akazawa Yuko, Yamaguchi Naoyuki, Ohnita Ken, Takeshima Fuminao, Hidaka Shigekazu, Matsushima Kayoko, Hashisako Mikiko, Tabata Kazuhiro, Nagayasu Takeshi, Fukuoka Junya, Nakao Kazuhiko, Expression of CPOX and PEPT1 Is Associated With Detection of Upper Gastrointestinal Carcinomas By 5-Aminolevlinic Acid Induced-Photodynamic Diagnosis, GASTROINTESTINAL ENDOSCOPY, 10.1016/j.gie.2016.03.687, 83, 5, AB488-AB488, 2016.05. |
| 2. |
Tomoyuki Fujisawa, Yasuoki Horiike, Ryoko Egashira, Hiromitsu Sumikawa, Tae Iwasawa, Shoichiro Matsushita, Hiroaki Sugiura, Kensuke Kataoka, Mikiko Hashisako, Hideki Yasui, Hironao Hozumi, Masato Karayama, Yuzo Suzuki, Kazuki Furuhashi, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Takafumi Suda, Radiological pleuroparenchymal fibroelastosis-like lesion in idiopathic interstitial pneumonias., Respiratory research, 10.1186/s12931-021-01892-9, 22, 1, 290-290, 2021.11, BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is characterised by predominant upper lobe pleural and subpleural lung parenchymal fibrosis. Radiological PPFE-like lesion has been associated with various types of interstitial lung diseases. However, the prevalence and clinical significance of radiological PPFE-like lesion in patients with idiopathic interstitial pneumonias (IIPs) are not fully understood. We aimed to determine the prevalence and clinical impact on survival of radiological PPFE-like lesion in patients with IIPs. METHODS: A post-hoc analysis was conducted using data from the Japanese nationwide cloud-based database of patients with IIPs. All the patients in the database were diagnosed as having IIPs by multidisciplinary discussion. Patients diagnosed with idiopathic PPFE were excluded. Clinical data and chest computed tomography (CT) image of 419 patients with IIPs were analysed. The presence of radiological PPFE-like lesion was independently evaluated by two chest radiologists blind to the clinical data. RESULTS: Of the 419 patients with IIPs, radiological PPFE-like lesions were detected in 101 (24.1%) patients, mainly in idiopathic pulmonary fibrosis (IPF) and unclassifiable IIPs, but less in idiopathic nonspecific interstitial pneumonia. Prognostic analyses revealed that radiological PPFE-like lesion was significantly associated with poor outcome in patients with IIPs, which was independent of age, IPF diagnosis and %FVC. In survival analyses, the patients with radiological PPFE-like lesions had poor survival compared with those without (log-rank, p |
| 3. |
Yuichi Yamada, Izumi Kinoshita, Yoshiko Miyazaki, Yuki Tateishi, Yusuke Kuboyama, Takeshi Iwasaki, Kenichi Kohashi, Hidetaka Yamamoto, Shin Ishihara, Yu Toda, Yoshihiro Ito, Yosuke Susuki, Kengo Kawaguchi, Mikiko Hashisako, Yui Yamada-Nozaki, Daisuke Kiyozawa, Taro Mori, Takeo Yamamoto, Kenji Tsuchihashi, Kazumi Kuriwaki, Munenori Mukai, Masataka Kawai, Keiko Suzuki, Hirotake Nishimura, Kenji Bando, Junya Masumoto, Mana Fukushima, Junichi Motoshita, Hiroki Mori, Akira Shiose, Yoshinao Oda, Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases., Virchows Archiv : an international journal of pathology, 10.1007/s00428-022-03293-9, 480, 4, 919-925, 2022.04, Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.. |
| 4. |
Ritsu Ibusuki, Yasuto Yoneshima, Mikiko Hashisako, Norikazu Matsuo, Taishi Harada, Yuko Tsuchiya-Kawano, Junji Kishimoto, Keiichi Ota, Yoshimasa Shiraishi, Eiji Iwama, Kentaro Tanaka, Yoshinao Oda, Isamu Okamoto, Association of thyroid transcription factor-1 (TTF-1) expression with efficacy of PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in advanced non-squamous non-small cell lung cancer., Translational lung cancer research, 10.21037/tlcr-22-393, 11, 11, 2208-2215, 2022.11, BACKGROUND: Thyroid transcription factor-1 (TTF-1) expression in advanced non-squamous non-small cell lung cancer (NSCLC) has been associated with the efficacy of pemetrexed plus platinum chemotherapy. However, the relation between TTF-1 expression and efficacy of the combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors plus pemetrexed and platinum chemotherapy, a standard first-line treatment regimen for advanced non-squamous NSCLC, has remained unclear. METHODS: We retrospectively evaluated TTF-1 expression in tumor tissue of patients with advanced or recurrent non-squamous NSCLC treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting. Clinical characteristics and pathological data for each patient were assessed, and progression-free survival (PFS) was evaluated. Bias due to patient background was minimized by application of inverse probability of treatment weighting (IPTW) analysis. RESULTS: A total of 122 patients, 75 (61.5%) of whom were positive for TTF-1 immunostaining in tumor specimens, was included in this multicenter study. At the time of analysis, 89 (73.0%) patients had experienced progression events and 44 (36.1%) had died [median follow-up 14.6 months (range, 0.53-29.5 months)]. PFS was longer for TTF-1-positive patients than for TTF-1-negative patients [median, 12.2 vs. 6.0 months; hazard ratio (HR) =0.63 (95% CI: 0.37-1.06); log-rank P=0.028]. IPTW-adjusted PFS was significantly longer for TTF-1-positive than for TTF-1-negative patients [HR =0.62 (95% CI: 0.46-0.83); log-rank P=0.024]. CONCLUSIONS: TTF-1 expression in advanced non-squamous NSCLC can serve as a basis for prediction of PFS in patients treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy in the first-line setting.. |
| 5. |
Takayuki Nakanishi, Yasuto Yoneshima, Koji Okamura, Toyoshi Yanagihara, Mikiko Hashisako, Takeshi Iwasaki, Naoki Haratake, Shun Mizusaki, Keiichi Ota, Eiji Iwama, Tomoyoshi Takenaka, Kentaro Tanaka, Tomoharu Yoshizumi, Yoshinao Oda, Isamu Okamoto, MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma., Cancer science, 10.1111/cas.15921, 2023.08, Treatment with immune checkpoint inhibitors induces a durable response in some patients with non-small-cell lung cancer, but eventually gives rise to drug resistance. Upregulation of CD155 expression is implicated as one mechanism of resistance to programmed death receptor-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors, and it is therefore important to characterize the mechanisms underlying regulation of CD155 expression in tumor cells. The aim of this study was to identify microRNAs (miRNAs) that might regulate CD155 expression at the posttranscriptional level in lung cancer. Comprehensive miRNA screening with target prediction programs and a dual-luciferase reporter assay identified miR-346, miR-328-3p, miR-326, and miR-330-5p as miRNAs that bind to the 3'-UTR of CD155 mRNA. Forced expression of these miRNAs suppressed CD155 expression in lung cancer cell lines. Immunohistochemical staining of CD155 in tissue specimens from 57 patients with lung adenocarcinoma revealed the median tumor proportion score for CD155 to be 68%. The abundance of miR-326 in these specimens with a low level of CD155 expression was significantly greater than in specimens with a high level (p |
| 6. |
Mikiko Hashisako, Takeshi Iwasaki, Takamasa Matsumoto, Yuichi Yamada, Takumi Miyamoto, Midori Taniguchi, Chiemi Oishi, Yoshinao Oda, Comparison of Akt/mammalian target of rapamycin/4E-binding protein 1 pathway signal activation in round stromal and surface cells in patients with sclerosing pneumocytoma., Pathology, research and practice, 10.1016/j.prp.2023.154384, 244, 154384-154384, 2023.04, Sclerosing pneumocytoma (SP) is a rare benign epithelial tumor of the lung, and approximately 40 % of patients with SP present with AKT1 E17K mutation. SP cells comprise proliferated surface and round stromal cells. To elucidate the role of signal transductions and to identify the difference between surface and stromal cells, the current study aimed to investigate the activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 signaling pathway in SP. METHODS: The molecular and pathological characteristics of SP in 12 patients were analyzed. AKT1 gene analysis revealed AKT1 E17K mutation in four cases. Immunohistochemical analysis revealed that tumor cells were cytoplasmic positive for pAkt, pmTOR, p4EBP1, and pS6RP. The surface cells had a significantly higher expression of pmTOR (p = 0.002) and a significantly lower expression of p4EBP1 (p = 0.017) than stromal cells. SP without AKT1 E17K mutation had a higher positive correlation with pacts, p4EBP1, pmTOR, and pS6RP expression than SP with AKT1 E17K mutation. These findings may be attributed to the aberrant activation of the Akt/mTOR pathway due to AKT1 E17K mutations. Hence, both surface and round stromal cells have tumorigenic characteristics, and differences in these characteristics may contribute to variations in tumor growth and the morphology and angiogenesis of SP.. |
| 7. |
Satoshi Anai, Mikiko Hashisako, Satoshi Ikegame, Kentarou Wakamatsu, Nobuhiko Nagata, Yoichi Nakanishi, Akira Kajiki, Mantle cell lymphoma involvement of the pleura and tuberculous pleurisy with pulmonary tuberculosis: a case report and literature review., Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 10.1007/s10156-011-0308-0, 18, 2, 258-64, 2012.04, A 78-year-old Japanese woman was admitted to our hospital for fever, dry cough, and right pleural effusion. She was diagnosed with mantle cell lymphoma (MCL) at 73 years of age and was treated with carcinostatics, but MCL was refractory. Chest computed tomography (CT) on admission revealed a localized trabecular shadow in the middle lobe of the right lung and right pleural effusion with thickened visceral pleura. Right pleural effusion was exudative, lymphocytes were dominant, and adenosine deaminase isoenzymes were elevated. (18)F-fluorodeoxyglucose positron emission tomography/CT revealed positive findings in the right thickened visceral pleura and right middle lobe. We suspected tuberculosis, but bronchoscopy revealed that the washing fluid was negative for Ziehl-Neelsen staining. Thoracoscopy under local anesthesia revealed redness on the parietal and visceral pleura and fibrin network. Pathological findings from pleural biopsy included granulomas, Langhans-type giant cells, and diffuse invasion of lymphocytes with atypical nuclei. Immunophenotypes were CD5(+), CD10(-), CD19(+), CD20(+), λ(+), CD25(+) by flow cytometry and CD20(+), CD45RO(-), cyclin D1(+), bcl2(+), bcl6(-) by immunohistochemistry. We diagnosed MCL involvement of the pleura, and highly suspected tuberculous pleurisy. The patient received antituberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol. After 4 weeks, culture of bronchoscopy washing fluid was positive for Mycobacterium tuberculosis. We diagnosed pulmonary tuberculosis. Patients with malignant lymphoma are vulnerable to tuberculosis. In addition to diagnosing MCL involvement of the pleura, it is important to consider the possibility of complication with tuberculosis.. |
| 8. |
Mikiko Hashisako, Kentarou Wakamatsu, Satoshi Ikegame, Hiroyuki Kumazoe, Nobuhiko Nagata, Akira Kajiki, Flare phenomenon following gefitinib treatment of lung adenocarcinoma with bone metastasis., The Tohoku journal of experimental medicine, 228, 2, 163-8, 2012.10, The skeleton is the most common site for distant metastasis in patients with cancer. To detect bone metastasis and evaluate the efficacy of treatment, we usually use bone scintigraphy and check serum alkaline phosphatase (ALP). However, such evaluation is sometimes difficult due to flare phenomenon. A 61-year-old male was referred to our department with a suspected diagnosis of lung cancer. Following thorough examinations, he was diagnosed with primary lung cancer (adenocarcinoma, Stage IV) and found to have a mutation in the epidermal growth factor receptor gene at exon 21 (L858R). After initiating treatment with oral gefitinib, ALP increased and peaked at 3,592 U/L by 3 weeks and decreased thereafter. At 4 weeks following treatment initiation, bone scintigraphy revealed a marked increase in abnormal accumulation of (99m)Tc-polyphosphate, but the primary tumor and metastases in regions other than the bone were reduced. At 9 weeks after treatment initiation, abnormal accumulations was improved in bone scintigraphy, and computed tomography revealed osteoblastic changes consistent with the accumulated lesion observed by bone scintigraphy. After initiating cancer treatment for bone metastasis, it is not uncommon to observe transient asynchronous accumulation in bone scintigraphy or transient increases in ALP in patients who ultimately respond to the treatment. These changes are called flare phenomenon, and documented in patients with prostate cancer or breast cancer receiving treatment. When determining the efficacy of treatments that target carcinomas with bone metastases, it is important to note that flare phenomenon is often indistinguishable from disease progression indicators.. |
| 9. |
Shiho Toyama, Ayuko Takatani, Tomohiro Koga, Mizuna Eguchi, Momoko Okamoto, Sosuke Tsuji, Yushiro Endo, Toshimasa Shimizu, Remi Sumiyoshi, Takashi Igawa, Shin-Ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Hideki Nakamura, Tomoki Origuchi, Masako Furuyama, Maiko Tabuchi, Shinichiro Kobayashi, Kengo Kanetaka, Mikiko Hashisako, Kuniko Abe, Daisuke Niino, Shinya Sato, Yasushi Miyazaki, Atsushi Kawakami, Gastric Perforation due to Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder during the Treatment of Rheumatoid Arthritis., Internal medicine (Tokyo, Japan), 10.2169/internalmedicine.2782-19, 58, 22, 3331-3336, 2019.11, A 71-year-old woman being treated with methotrexate (MTX) and tacrolimus (TAC) for rheumatoid arthritis (RA) was admitted to our hospital and underwent surgery for gastric perforation and peritonitis. An endoscopic examination six days post-surgery showed an extensive ulcer in the stomach, and a biopsy revealed diffused large B-cell lymphoma. We diagnosed her with immunodeficiency-associated lymphoproliferative disorder (LPD) and discontinued the MTX and TAC. She underwent gastrectomy due to stenosis approximately two months after the first operation, but the histopathological findings of lymphoma had disappeared. LPD should be considered as a potential cause of gastric perforation during RA treatment.. |
| 10. |
Midori Akagi, Masataka Umeda, Mikiko Hashisako, Kazusato Hara, Sousuke Tsuji, Yushiro Endo, Ayuko Takatani, Toshimasa Shimizu, Shoichi Fukui, Tomohiro Koga, Shin-Ya Kawashiri, Naoki Iwamoto, Takashi Igawa, Kunihiro Ichinose, Mami Tamai, Hideki Nakamura, Tomoki Origuchi, Daisuke Niino, Atsushi Kawakami, Drop Head Syndrome as a Rare Complication in Mixed Connective Tissue Disease., Internal medicine (Tokyo, Japan), 10.2169/internalmedicine.3626-19, 59, 5, 729-732, 2020.03, A 54-year-old woman developed drop head syndrome (DHS), Raynaud's phenomenon and creatine kinase (CK) elevation. She did not meet the international classification criteria of dermatomyositis/polymyositis, as we observed no muscle weakness, grasping pain or electromyography abnormality in her limbs, and anti-aminoacyl tRNA synthetase (ARS) antibody was negative. Cervical magnetic resonance imaging and a muscle biopsy of the trapezius muscle revealed myositis findings as the only clinical observations in muscle. These findings, along with her anti-U1-ribonucleoprotein (RNP) antibody positivity and leukopenia, resulted in a diagnosis of mixed connective tissue disease (MCTD). Prednisolone treatment significantly improved her myositis. To our knowledge, this is the first report of DHS as the only muscle complication of MCTD.. |
| 11. |
Yuki Tateishi, Yuichi Yamada, Masato Katsuki, Takuya Nagata, Hidetaka Yamamoto, Kenichi Kohashi, Yutaka Koga, Mikiko Hashisako, Daisuke Kiyozawa, Taro Mori, Yusuke Kuboyama, Ayumi Kakinokizono, Yoshiko Miyazaki, Aina Yamaguchi, Hiroyuki Tsutsui, Toshiharu Ninomiya, Hironobu Naiki, Yoshinao Oda, Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution., Pathology, research and practice, 10.1016/j.prp.2021.153635, 227, 153635-153635, 2021.09, AIM: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type. MATERIALS AND METHODS: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and β2-microglobulin was performed for all cases. RESULTS: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of β2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern. CONCLUSION: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies.. |
| 12. |
Shohei Yoshiya, Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Takeshi Kurihara, Takeo Toshima, Noboru Harada, Mikiko Hashisako, Hirotoshi Yonemasu, Kengo Fukuzawa, Yoshinao Oda, Masaki Mori, Impact of Capicua on Pancreatic Cancer Progression., Annals of surgical oncology, 10.1245/s10434-020-09339-z, 28, 6, 3198-3207, 2021.06, BACKGROUND: The transcription factor capicua (CIC) regulates mammalian development and homeostasis. Growing evidence shows that CIC suppresses various human cancers by directly repressing the downstream cancer-related target genes. This study investigated the clinical and biologic significance of CIC expression in pancreatic cancer (PC). METHODS: The study reviewed 132 patients with PC who underwent curative resection. The patients were divided into two groups according to CIC immunoreactivity score by immunohistochemistry, and the associations between CIC expression, clinicopathologic characteristics, and postoperative prognosis were investigated. Moreover, the influence of CIC expression on the malignant potential of PC cells was assessed with cell proliferation, motility assays, and use of quantitative real time-polymerase chain reaction and Western blot on the downstream target genes of CIC in knockdown experiments. RESULTS: The low-CIC expression group showed a higher proportion of lymphatic invasion (72.9% vs. 53.1%; p = 0.024), intrapancreatic neural invasion (94.1% vs. 81.3%; p = 0.021), and extrapancreatic plexus invasion (30.9% vs. 7.8%; p = 0.0006) than the high-CIC expression group as well as significantly worse overall survival (p = 0.0002) and recurrence-free survival (p = 0.0041) rates. Low CIC expression was an independent risk factor for poor prognosis (p = 0.038). Pancreatic cancer cells with knockdown CIC significantly enhanced cell motilities and cell cycle progression, promoted expression levels of ETV4 and MMP-9, and induced EMT. CONCLUSIONS: The study elucidated the association of low CIC expression with a poor prognosis for patients with PC and suggested that the CIC-ETV4-MMP-9 axis might control PC progression.. |
| 13. |
Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Ito, Yuki Kuma, Yui Yamada-Nozaki, Yutaka Koga, Mikiko Hashisako, Daisuke Kiyozawa, Daichi Kitahara, Fumiya Narutomi, Yusuke Kuboyama, Takahito Nakamura, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Fumiyoshi Fushimi, Kenichi Taguchi, Kenichi Nishiyama, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, Toru Iwaki, Yoshinao Oda, Histological background of dedifferentiated solitary fibrous tumour., Journal of clinical pathology, 10.1136/jclinpath-2020-207311, 75, 6, 397-403, 2021.05, AIMS: Dedifferentiation is a histological phenomenon characterised by abrupt transition of histology to a sarcomatous component with high-grade malignant potential in solitary fibrous tumour (SFT). The authors histologically reviewed SFT cases to reveal the histological background of dedifferentiated SFTs. METHODS: Clinicopathological and histopathological findings of 145 SFT cases were reviewed. Immunohistochemical staining and genetic analysis were also performed. RESULTS: The non-dedifferentiated components showed a cellular component in 45 of 145 (31%), high mitotic rate (≥4/10 high-powered field) in 12 of 145 (8.2%) tumours, necrosis in 7 of 145 (4.8%) tumours, multinodular growth pattern in 39 of 132 (29.5%) available tumours and intratumoural fibrous septa in 37 of 131 (28.2%). Immunohistochemically, the non-dedifferentiated components were positive for CD34 in 128 of 141 (90.7%), bcl-2 in 101 of 133 (75.9%), nuclear pattern of β-catenin in 64 of 127 (50.3%) and p16 in 22 of 140 (15.7%). Loss of Rb protein expression was detected in 17 of 110 (15.4%) cases. Statistically, cellular component, multinodular structure, p16 overexpression and Rb protein loss were significantly associated with dedifferentiation. Moreover, cellular component and multinodular structure were significantly associated with p16 overexpression and Rb protein loss. All the non-deddifferentiated components showed wild type of p53 expression. The dedifferentiated components of all 10 dedifferentiated tumours presented positivity for p16 in 9 of 10 (90%) and mutational type of p53 in 5 of 10 (50%). Loss of Rb protein expression was detected in 6 of 10 (60%). CONCLUSIONS: The authors propose that cellular or multinodular transformation may be associated with dedifferentiation. They also suggest that cellular and multinodular transformation may be associated with p16 overexpression and Rb downregulation.. |
| 14. |
Masahiro Tahara, Yoshihisa Fujino, Kei Yamasaki, Keishi Oda, Takashi Kido, Noriho Sakamoto, Toshinori Kawanami, Kensuke Kataoka, Ryoko Egashira, Mikiko Hashisako, Yuzo Suzuki, Tomoyuki Fujisawa, Hiroshi Mukae, Takafumi Suda, Kazuhiro Yatera, Exposure to PM2.5 is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case-control study., Respiratory research, 10.1186/s12931-021-01671-6, 22, 1, 80-80, 2021.03, BACKGROUND: Short-term exposure to ozone and nitrogen dioxide is a risk factor for acute exacerbation (AE) of idiopathic pulmonary fibrosis (AE-IPF). The comprehensive roles of exposure to fine particulate matter in AE-IPF remain unclear. We aim to investigate the association of short-term exposure to fine particulate matter with the incidence of AE-IPF and to determine the exposure-risk time window during 3 months before the diagnosis of AE-IPF. METHODS: IPF patients were retrospectively identified from the nationwide registry in Japan. We conducted a case-control study to assess the correlation between AE-IPF incidence and short-term exposure to eight air pollutants, including particulate matter |
| 15. |
Junya Tominaga, Tae Iwasawa, Makiko Murota, Hiroaki Arakawa, Takeshi Johkoh, Yasuhiko Yamano, Yoshiaki Zaizen, Kazuya Ichikado, Mikiko Hashisako, Yasuhiro Kondoh, Kensuke Kataoka, Masaki Okamoto, Kiminori Fujimoto, Junya Fukuoka, Computed tomography findings of current nonspecific interstitial pneumonia based on the 2013 updated classification of idiopathic interstitial pneumonias: What is a characteristic of previously diagnosed nonspecific interstitial pneumonia excluded from the updated classification., Japanese journal of radiology, 10.1007/s11604-020-01036-x, 39, 1, 47-55, 2021.01, PURPOSE: To evaluate computed tomography (CT) findings of nonspecific interstitial pneumonia (NSIP) based on the current classification of idiopathic interstitial pneumonias (IIPs) and elucidate a characteristic of previously diagnosed NSIP excluded from the current classification. MATERIALS AND METHODS: The study included 74 patients with biopsy-proven NSIP (idiopathic NSIP [I-NSIP], 39 patients; NSIP associated with connective tissue disease [CTD-NSIP], 35 patients). Among patients who were compatible with the current classification of IIPs, 29 and 21 were categorized as having current I-NSIP and current CTD-NSIP, respectively. The remaining 24 patients were categorized as having previous I-NSIP or previous CTD-NSIP due to the primary pathologic diagnosis of cellular NSIP or associated findings of acute inflammatory changes. CT findings were evaluated and compared among the four groups. RESULTS: Current I-NSIP was indicated by ground-glass attenuation and reticulation with traction bronchiectasis/bronchiolectasis in predominantly peribronchovascular areas of the lower lung zone. The previous I-NSIP group tended to show broader airspace consolidation than the current I-NSIP group (p = 0.068). The previous CTD-NSIP group showed significantly broader airspace consolidation than the current I-NSIP group (p = 0.035). CONCLUSION: Broad airspace consolidation is a characteristic of previously diagnosed CTD-NSIP excluded from the current classification of IIPs.. |
| 16. |
Masahiro Tahara, Yoshihisa Fujino, Kei Yamasaki, Keishi Oda, Takashi Kido, Noriho Sakamoto, Toshinori Kawanami, Kensuke Kataoka, Ryoko Egashira, Mikiko Hashisako, Yuzo Suzuki, Tomoyuki Fujisawa, Hiroshi Mukae, Takafumi Suda, Kazuhiro Yatera , Exposure to PM 2.5 is a risk factor for acute exacerbation of surgically diagnosed idiopathic pulmonary fibrosis: a case-control study, Respiratory Research, 10.1186/s12931-021-01671-6, 2021.03. |
| 17. |
Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Ito, Yuki Kuma, Yui Yamada-Nozaki, Yutaka Koga, Mikiko Hashisako, Daisuke Kiyozawa, Daichi Kitahara, Fumiya Narutomi, Yusuke Kuboyama, Takahito Nakamura, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Fumiyoshi Fushimi, Kenichi Taguchi, Kenichi Nishiyama, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, Toru Iwaki, Yoshinao Oda, Histological background of dedifferentiated solitary fibrous tumour., Journal of clinical pathology, 10.1136/jclinpath-2020-207311, 2021.05. |
| 18. |
Noriyuki Enomoto, Ryoko Egashira, Kazuhiro Tabata, Mikiko Hashisako, Masashi Kitani, Yuko Waseda, Tamotsu Ishizuka, Satoshi Watanabe, Kazuo Kasahara, Shinyu Izumi, Akira Shiraki, Atsushi Miyamoto, Kazuma Kishi, Tomoo Kishaba, Chikatosi Sugimoto, Yoshikazu Inoue, Kensuke Kataoka, Yasuhiro Kondoh, Yutaka Tsuchiya, Tomohisa Baba, Hiroaki Sugiura, Tomonori Tanaka, Hiromitsu Sumikawa, Takafumi Suda, Analysis of systemic lupus erythematosus-related interstitial pneumonia a retrospective multicentre study, Scientific reports, 10.1038/s41598-019-43782-7, 9, 1, 7355-7355, 2019.12, Thoracic diseases in patients with systemic lupus erythematosus (SLE), especially interstitial pneumonia (SLE-IP), are rare and have been poorly studied. The aims of this multicentre study were to evaluate SLE-IP and elucidate its clinical characteristics and prognosis. Fifty-five patients with SLE-IP who had attended the respiratory departments of participating hospitals were retrospectively evaluated in this multicentre study. Clinical information, high-resolution computed tomography (HRCT), and surgical lung biopsy/autopsy specimens were analysed by respiratory physicians, pulmonary radiologists, and pulmonary pathologists. IP patterns on HRCT and lung specimens were classified based on the international classification statement/guideline for idiopathic interstitial pneumonias. The most frequent form of SLE-IP at diagnosis was chronic IP (63.6%), followed by subacute (20.0%), and acute IP (12.7%). Radiologically, the most common HRCT pattern was “Unclassifiable” (54%). Histologically, “Unclassifiable” was the most frequently found (41.7%) among 12 patients with histologically proven IP. Interestingly, accompanying airway diseases were present in nine of these patients (75%). In multivariate analysis, current smoking (hazard ratio [HR] 6.105, p = 0.027), thrombocytopenia (HR 7.676, p = 0.010), anti-double-strand DNA titre (HR 0.956, p = 0.027), and nonspecific interstitial pneumonia (NSIP) + organizing pneumonia (OP) pattern on HRCT (vs. NSIP, HR 0.089, p = 0.023) were significant prognostic factors. In conclusion, chronic IP was the most frequent form of IP in patients with SLE-IP, and “Unclassifiable” was the commonest pattern radiologically and histologically.. |
| 19. |
Yuichi Yamada, Kenichi Kohashi, Izumi Kinoshita, Hidetaka Yamamoto, Takeshi Iwasaki, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yoshihiro Itou, Yutaka Koga, Mikiko Hashisako, Yui Nozaki, Daisuke Kiyozawa, Daichi Kitahara, Takeshi Inoue, Munenori Mukai, Yumi Honda, Gouji Toyokawa, Kenji Tsuchihashi, Yoshifumi Matsushita, Fumiyoshi Fushimi, Kenichi Taguchi, Sadafumi Tamiya, Yumi Oshiro, Masutaka Furue, Yasuharu Nakashima, Satoshi Suzuki, Toru Iwaki, Yoshinao Oda, Clinicopathological review of solitary fibrous tumors dedifferentiation is a major cause of patient death, Virchows Archiv, 10.1007/s00428-019-02622-9, 475, 4, 467-477, 2019.10, Solitary fibrous tumor (SFT) is a soft-tissue neoplasm of intermediate malignant potential, presenting a wide histopathological spectrum. Poorer prognosis of hemangiopericytoma of the central nervous system (CNS), hypoglycemic SFT, and dedifferentiation are well-known characters of SFT, but their clinical significance were not demonstrated enough by large-sized study. Here, the clinicopathological features of SFTs are reviewed and the relationship between genetics and clinicopathological features is examined using 145 SFT cases. All cases were STAT6 IHC-positive and/or NAB2-STAT6 fusion gene-positive. Tumor location was classified into three categories: 30 pleuropulmonary, 96 non-pleuropulmonary/non-central nervous system (CNS), and 18 CNS tumors. The tumor developed recurrence in 21 of 93 available cases (22.5%), metastasis in 11 of 93 (11.8%), and tumor death in 9 of 93 (9.6%). Hypoglycemia occurred in 2 primary tumors and 1 metastatic tumor among 63 reviewable cases, and dedifferentiation occurred in 10 cases (6.8%) including 6 primary tumors, 2 recurrent tumors, and 2 metastatic tumors. Recurrence was positively associated with CNS location (p = 0.0109) and hypoglycemia (p = 0.001); metastasis was positively associated with CNS location (p = 0.0231), hypoglycemia (p |
| 20. |
Tomoyuki Fujisawa, Kazutaka Mori, Masashi Mikamo, Takashi Ohno, Kensuke Kataoka, Chikatoshi Sugimoto, Hideya Kitamura, Noriyuki Enomoto, Ryoko Egashira, Hiromitsu Sumikawa, Tae Iwasawa, Shoichiro Matsushita, Hiroaki Sugiura, Mikiko Hashisako, Tomonori Tanaka, Yasuhiro Terasaki, Shinobu Kunugi, Masashi Kitani, Ryo Okuda, Yasuoki Horiike, Yasunori Enomoto, Hideki Yasui, Hironao Hozumi, Yuzo Suzuki, Yutaro Nakamura, Junya Fukuoka, Takeshi Johkoh, Yasuhiro Kondoh, Takashi Ogura, Yoshikazu Inoue, Yoshinori Hasegawa, Naohiko Inase, Sakae Homma, Takafumi Suda, Nationwide cloud-based integrated database of idiopathic interstitial pneumonias for multidisciplinary discussion, The European respiratory journal, 10.1183/13993003.02243-2018, 53, 5, 2019.05, Multidisciplinary discussion (MDD) requiring close communication between specialists (clinicians, radiologists and pathologists) is the gold standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). However, MDD by specialists is not always feasible because they are often separated by time and location. An online database would facilitate data sharing and MDD. Our aims were to develop a nationwide cloud-based integrated database containing clinical, radiological and pathological data of patients with IIPs along with a web-based MDD system, and to validate the diagnostic utility of web-based MDD in IIPs.Clinical data, high-resolution computed tomography images and lung biopsy slides from patients with IIPs were digitised and uploaded to separate servers to develop a cloud-based integrated database. Web-based MDD was performed using the database and video-conferencing to reach a diagnosis.Clinical, radiological and pathological data of 524 patients in 39 institutions were collected, uploaded and incorporated into the cloud-based integrated database. Subsequently, web-based MDDs with a pulmonologist, radiologist and pathologist using the database and video-conferencing were successfully performed for the 465 cases with adequate data. Overall, the web-based MDD changed the institutional diagnosis in 219 cases (47%). Notably, the MDD diagnosis yielded better prognostic separation among the IIPs than did the institutional diagnosis.This is the first study of developing a nationwide cloud-based integrated database containing clinical, radiological and pathological data for web-based MDD in patients with IIPs. The database and the web-based MDD system that we built made MDD more feasible in practice, potentially increasing accurate diagnosis of IIPs.. |
| 21. |
Mio Mori, Hideyuki Hayashi, Minoru Fukuda, Sumihisa Honda, Takeshi Kitazaki, Kazuto Shigematsu, Naohiro Matsuyama, Mayumi Otsubo, Takeshi Nagayasu, Mikiko Hashisako, Kazuhiro Tabata, Masataka Uetani, Kazuto Ashizawa, Clinical and computed tomography characteristics of non-small cell lung cancer with ALK gene rearrangement Comparison with EGFR mutation and ALK/EGFR-negative lung cancer, Thoracic Cancer, 10.1111/1759-7714.13017, 10, 4, 872-879, 2019.04, Background: The study was conducted to evaluate the clinical and computed tomography (CT) findings of non-small cell lung cancer (NSCLC) patients to distinguish between ALK gene rearrangement, EGFR mutation, and non-ALK/EGFR (no genetic abnormalities). Methods: We enrolled 201 patients with primary NSCLC who had undergone molecular testing for both ALK gene rearrangement and EGFR mutation. The clinical features and CT findings of the main lesion and associated pulmonary abnormalities were investigated. Results: Female gender (P = 0.0043 vs. non-ALK/EGFR), young age (P = 0.0156 vs. EGFR), and a light or never smoking history (P = 0.0039 vs. non-ALK/EGFR) were significant clinical characteristics of NSCLC with ALK gene rearrangement. The significant CT characteristics compared to NSCLC with EGFR mutation were a large mass (P = 0.0155), solid mass (P = 0.0048), and no air bronchogram (P = 0.0148). A central location (P = 0.0322) and lymphadenopathy (P = 0.0353) were also more frequently observed. Coexisting emphysema was significantly less frequent in NSCLC patients with ALK gene rearrangement (P = 0.0135) than non-ALK/EGFR. Conclusions: NSCLC with ALK gene rearrangement was more likely to develop in younger women with a light or never smoking history. The characteristic CT findings of NSCLC with ALK gene rearrangement were a large solid mass, less air bronchogram, a central location, and lymphadenopathy.. |
| 22. |
Yuri Tachibana, Hiroyuki Taniguchi, Yasuhiro Kondoh, Kensuke Kataoka, Naoki Hamada, Toshihiro Hashiguchi, Kazuya Ichikado, Tomoo Kishaba, Shuntaro Sato, Emiko Udo, Mikiko Hashisako, Junya Fukuoka, Pulmonary interstitial emphysema is a risk factor for poor prognosis and a cause of air leaks, Respiratory Investigation, 10.1016/j.resinv.2019.03.008, 57, 5, 444-450, 2019.01, Background: Pulmonary interstitial emphysema is a rare, abnormal condition in which air pressure from the alveolar airspace tears the adjacent interstitial tissues of the lung and causes the formation of cystic spaces. Pulmonary interstitial emphysema is a known indication for mechanical ventilation in premature infants with neonatal respiratory distress syndrome, and it can be observed in various types of interstitial lung disease. Nevertheless, its pathogenesis and clinical impact remain unknown. Methods: We reviewed data from 433 cases of interstitial lung disease from an external consultation archive. Multidisciplinary diagnosis along with clinical and follow-up data, including events of air leaks such as pneumothorax and mediastinal emphysema, were obtained and compared to those of 150 control cases of interstitial lung disease without pulmonary interstitial emphysema. Results: We found 22 (5.1%)cases of interstitial lung disease with pulmonary interstitial emphysema. The diagnoses included idiopathic pulmonary fibrosis (5/22 [22.7%]), pleuroparenchymal fibroelastosis (4/22 [18.2%]), chronic hypersensitivity pneumonia (4/22 [18.2%]), and others (9/22 [40.9%]). Cases involving pulmonary interstitial emphysema demonstrated a significantly higher frequency of air leaks than did those without pulmonary interstitial emphysema (12/22 [54.5%]versus 23/150 [15.3%]; P |
| 23. |
Kumi Ogihara, Hajime Isomoto, Hiroki Kurumi, Tsutomu Kanda, Mikiko Hashisako, Kazuhiro Tabata, Hiroyuki Ishii, Ken Ohnita, Naoyuki Yamaguchi, Yuko Akazawa, Kayoko Matsushima, Fuminao Takeshima, Masaki Kunizaki, Shigekazu Hidaka, Atsushi Nanashima, Junya Fukuoka, Takeshi Nagayasu, Kazuhiko Nakao, Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis, Photodiagnosis and Photodynamic Therapy, 10.1016/j.pdpdt.2017.04.003, 19, 15-21, 2017.09, Background 5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. Methods Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. Results Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. Conclusion Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.. |
| 24. |
Mikiko Hashisako, Tomonori Tanaka, Yasuhiro Terasaki, Toshimasa Uekusa, Rosane D. Achcar, Bassam I. Aswad, Hanaa S. Bamefleh, Vera L. Capelozzi, John C. English, Alexandre T. Fabro, Kensuke Kataoka, Tomayoshi Hayashi, Yasuhiro Kondoh, Hiroyuki Taniguchi, Junya Fukuoka, Interobserver agreement of usual interstitial pneumonia diagnosis correlated with patient outcome, Archives of Pathology and Laboratory Medicine, 10.5858/arpa.2016-0012-OA, 140, 12, 1375-1382, 2016.12, Context. - The histopathologic criteria for idiopathic pulmonary fibrosis were revised in the American Thoracic Society/European Respiratory Society/Japan Respiratory Society/Latin American Thoracic Association guidelines in 2011. However, the evidence of diagnosis based on the guidelines needs further investigation. Objective. - To examine whether the revised histopathologic criteria for idiopathic pulmonary fibrosis improved interobserver agreement among pathologists and the predicted prognosis in patients with interstitial pneumonia. Design. - Twenty, consecutive, surgical lung-biopsy specimens from cases of interstitial pneumonia were examined for histologic patterns by 11 pathologists without knowledge of clinical and radiologic data. Diagnosis was based on American Thoracic Society/European Respiratory Society guidelines of 2002 and 2011. Pathologists were grouped by cluster analysis, and interobserver agreement and association to the patient prognosis were compared with the diagnoses for each cluster. Results. - The generalized κ coefficient of diagnosis for all pathologists was 0.23. If the diagnoses were divided into 2 groups: usual interstitial pneumonia (UIP)/probable UIP (the UIP group) or possible/not UIP (the non-UIP group), according to the 2011 guidelines, the κ improved to 0.37. The pathologists were subdivided into 2 clusters in which 1 showed an association between UIP group diagnosis and patient prognosis (P |
| 25. |
Akira Yoshikawa, Shuntaro Sato, Tomonori Tanaka, Mikiko Hashisako, Yukio Kashima, Tomoshi Tsuchiya, Naoya Yamasaki, Takeshi Nagayasu, Hiroshi Yamamoto, Junya Fukuoka, Breakdown of lung framework and an increase in pores of kohn as initial events of emphysema and a cause of reduction in diffusing capacity, International Journal of COPD, 10.2147/COPD.S114281, 11, 1, 2287-2294, 2016.09, Purpose: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. Conclusion: A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.. |
| 26. |
Hajime Isomoto, Atsushi Nanashima, Takemasa Senoo, Kumi Ogiwara, Mikiko Hashisako, Ken Ohnita, Naoyuki Yamaguchi, Masaki Kunizaki, Shigekazu Hidaka, Hiroko Fukuda, Hiroyuki Ishii, Kayoko Matsushima, Hitomi Minami, Yuko Akazawa, Fuminao Takeshima, Junya Fukuoka, Takeshi Nagayasu, Kazuhiko Nakao, In vivo fluorescence navigation of gastric and upper gastrointestinal tumors by 5-aminolevulinic acid mediated photodynamic diagnosis with a laser-equipped video image endoscope, Photodiagnosis and Photodynamic Therapy, 10.1016/j.pdpdt.2015.03.006, 12, 2, 201-208, 2015.06, Photodynamic diagnosis (PDD) is an imaging technology that is based on the fundamental biological features of cancer cells. Five-aminolevulinic acid (ALA), a precursor of photosensitizing protoporphyrin IX (PpIX) has been applied. In fact, ALA-mediated PDD provides good visualization for certain tumors. However, there have been few studies on clinical application of PDD for gastrointestinal (GI) cancers. This study was aimed to investigate the feasibility of ALA-mediated PDD for navigation of upper GI tumors. Materials and methods: Using a newly developed endoscope equipped with a blue laser light excitation, ALA-mediated PDD was conducted in 27 lesions from 23 patients with upper GI tumors including 2 Barrett's intramucosal cancers. ALA solution was given orally 3. h before PDD. All the adenocarcinomas came under clinical stage I, and the tumors were resected endoscopic submucosal dissection and/or laparoscopic surgery. Red fluorescence signal and intensity was assessed as for clinicopathological features of the cases. Results: The laser-based endoscopy could detect upper GI tumors as red fluorescent navigation (PDD-positive) in 23 of the 27 lesions. All but one intestinal typed tumors in histopathology were significantly PDD-positive, whereas each signet ring cell carcinoma was PDD-negative. There was a significant difference in tumor size between the PDD-positive and -negative tumors. The elevated lesions emitted significantly more intense fluorescence. Conclusions: Fluorescence navigation by ALA-mediated PDD provided sufficient detection of upper GI tumors in particular for the intestinal typed tumors. Thus, ALA-PDD using the blue laser-equipped endoscope offers a promising diagnostic tool.. |
