研究者詳細 - 山元　英崇

論文 - 山元　英崇

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Expression of CD5 in salivary gland tumors: an ancillary marker for carcinoma showing thymus-like differentiation (CASTLE) of the major salivary gland. 査読国際誌

Eiichi Sasaki, Hoshino Terada, Naoki Oishi, Akari Iwakoshi, Katsuhiro Masago, Hirokazu Matsushita, Hidetaka Yamamoto, Nobuhiro Hanai, Hisashi Tateyama

Virchows Archiv : an international journal of pathology 484 ( 6 ) 945 - 950 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Recently, cases of carcinoma showing thymus-like differentiation (CASTLE) occurring in major salivary glands have been identified. To assess the diagnostic value of CD5 immunohistochemistry in distinguishing salivary CASTLE from other types of salivary gland tumors, we evaluated CD5 expression in 109 salivary gland tumors, encompassing 23 different histological types, including salivary CASTLE. In addition, we reviewed 10 previously reported cases of salivary CASTLE. Most salivary CASTLE cases (10/11, 91%) showed strong CD5 expression. In contrast, 104 of 108 (96%) non-salivary CASTLE tumors were negative for CD5, while the remaining four tumors (3.7%), all of which were histologically Warthin tumors, showed focal positivity for CD5 with weak to moderate intensity. In conclusion, the findings in this study support the potential use of CD5 immunohistochemistry for distinguishing salivary CASTLE from other histological types of salivary gland tumors. Aberrant CD5 expression in this tumor may be linked to the tumor microenvironment.

DOI： 10.1007/s00428-023-03701-8

Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan 査読国際誌

Kenji Tsuchihashi, Mamoru Ito, Shuji Arita, Hitoshi Kusaba, Wataru Kusano, Takashi Matsumura, Takafumi Kitazono, Shohei Ueno, Ryosuke Taguchi, Tomoyasu Yoshihiro, Yasuhiro Doi, Kohei Arimizu, Hirofumi Ohmura, Tatsuhiro Kajitani, Kenta Nio, Michitaka Nakano, Kotoe Oshima, Shingo Tamura, Tsuyoshi Shirakawa, Hozumi Shimokawa, Keita Uchino, Fumiyasu Hanamura, Yuta Okumura, Masato Komoda, Taichi Isobe, Hiroshi Ariyama, Taito Esaki, Kazuki Hashimoto, Noritaka Komune, Mioko Matsuo, Keiji Matsumoto, Kaori Asai, Tadamasa Yoshitake, Hidetaka Yamamoto, Yoshinao Oda, Koichi Akashi, Eishi Baba

BMC Cancer 23 ( 1 ) 1046 - 1046 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Background

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy.

Methods

We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy.

Results

Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions.

Conclusion

The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

DOI： 10.1186/s12885-023-11528-4

その他リンク： https://link.springer.com/article/10.1186/s12885-023-11528-4/fulltext.html

An invasive presentation of parotid lymphadenoma: A first reported case. 査読国際誌

Hideoki Uryu, Minako Fujiwara, Ryutarou Uchi, Hidetaka Yamamoto, Torahiko Nakashima

Pathology, research and practice 250 154823 - 154823 2023年10月

記述言語：英語

Lymphadenoma, a rare benign tumor recognized in the WHO salivary gland tumor classification of 2005, poses diagnostic and treatment challenges due to its rarity and distinct histopathological characteristics. We report a unique case of lymphadenoma in a 45-year-old male patient who presented with a hard, painless tumor in the right parotid gland that had been present since he was 15 years old. Distinctively, MRI and CT imaging revealed signs of infiltration into the surrounding muscle tissues, challenging the traditional notion of lymphadenomas as tumors with clear boundaries. The histopathological examination identified the characteristic epithelial and lymphoid cell proliferation, suggestive of a lymphadenoma. However, the possibility of sebaceous differentiation due to faintly pale cells within the epithelial component was inconclusive. The tumor's invasive nature and the high risk of facial nerve paralysis associated with surgical resection led to the patient's decision against treatment. Findings from this case underline the need for caution in diagnosing lymphadenoma, given its potential to show invasive images and the risks associated with a malignant diagnosis based solely on these images. Furthermore, the observations from this case present new insights into the FDG-PET findings of lymphadenoma, contributing to the overall understanding of this rare tumor's clinical implications. Future studies are warranted to provide more clarity on this condition.

DOI： 10.1016/j.prp.2023.154823

HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx with Multisite Involvement 査読国際誌

Ryosuke Kuga, Hidetaka Yamamoto, Rina Jiromaru, Takahiro Hongo, Ryuji Yasumatsu, Mioko Matsuo, Kazuki Hashimoto, Midori Taniguchi, Takashi Nakagawa, Yoshinao Oda

American Journal of Surgical Pathology 47 ( 9 ) 955 - 966 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis (P=0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis (P=0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.

DOI： 10.1097/PAS.0000000000002086

Single-cell transcriptomics reveals granzyme K-expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD. 査読国際誌

Ryuichi Aoyagi, Takashi Maehara, Risako Koga, Ryusuke Munemura, Tadashi Tomonaga, Yuka Murakami, Atsushi Doi, Hidetaka Yamamoto, Tamotsu Kiyoshima, Shintaro Kawano, Seiji Nakamura

The Journal of allergy and clinical immunology 153 ( 2 ) 513 - 520 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Germinal center (GC) responses controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are crucial for the generation of high-affinity antibodies. Acquired immune responses to tissue-released antigens might be mainly induced in tertiary lymphoid organs (TLOs) with GCs in affected tissues. IgG4-related disease (IgG4-RD) demonstrates polarized isotype switching and TLOs in affected tissues. We performed single-cell transcriptomics of tissue-infiltrating T cells from these TLOs to obtain a comprehensive, unbiased view of tissue-infiltrating GC-Tfh cells. OBJECTIVE: To identify GC-Tfh-cell subsets in TLOs in patients with IgG4-RD using single-cell transcriptomics. METHODS: Single-cell RNA sequencing of sorted CD3+ T cells and multicolor immunofluorescence analysis were used to investigate CD4+CXCR5+Bcl6+ GC-Tfh cells in affected lesions from patients with IgG4-RD. RESULTS: Infiltrating CD4+CXCR5+Bcl6+ Tfh cells were divided into 5 main clusters. We detected HLA+ granzyme K+ (GZMK+) Tfh cells with cytotoxicity-associated features in patients with IgG4-RD. We also observed abundant infiltrating Tfr cells with suppressor-associated features in patients with IgG4-RD. These GZMK+ Tfh cells and Tfr cells clustered together in affected tissues from patients with IgG4-RD. CONCLUSIONS: This single-cell data set revealed a novel subset of HLA+GZMK+ cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting that infiltrating Tfr cells might suppress cytotoxic Tfh cells.

DOI： 10.1016/j.jaci.2023.08.019

Preferential B cell differentiation by combined immune checkpoint blockade for renal cell carcinoma is associated with clinical response and autoimmune reactions. 査読国際誌

Koki Uehara, Kenro Tanoue, Kyoko Yamaguchi, Hirofumi Ohmura, Mamoru Ito, Yuzo Matsushita, Kenji Tsuchihashi, Shingo Tamura, Hozumi Shimokawa, Taichi Isobe, Yoshihiro Shibata, Hiroshi Ariyama, Risa Tanaka, Hitoshi Kusaba, Hidetaka Yamamoto, Yoshinao Oda, Koichi Akashi, Eishi Baba

Cancer immunology, immunotherapy : CII 72 ( 11 ) 3543 - 3558 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Combined immune checkpoint blockade (ICB) is effective therapy for renal cell carcinoma (RCC). However, the dynamic changes in circulating B cells induced by combined ICB have not been clarified. The present study prospectively examined 22 patients scheduled to receive ICB for unresectable or metastatic RCC between March 2018 and August 2021. Eleven patients received combined therapy with anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab), and the other 11 patients received nivolumab monotherapy. Comprehensive phenotypes of circulating immune cells obtained prior to and after ICB therapy were analyzed by flow cytometry. Although the proportion of naïve B cells among total B cells was significantly decreased, that of switched memory B cells was significantly increased after combined therapy. In responders, the proportion of B cells among peripheral blood mononuclear cells was significantly higher prior to ICB therapy, and the proportion of switched memory B cells among total B cells tended to increase after ICB therapy. Of note, the proportion of plasmablasts among total B cells was significantly increased after ICB therapy in patients who developed severe immune-related adverse events (irAEs), and the proportion of B cells among peripheral blood decreased significantly. Furthermore, in four of five patients who developed immune-related hypophysitis following combined therapy, anti-pituitary antibody was detected in the serum. These results suggested that immune-related hypophysitis was closely related to the increase in circulating plasmablasts. Collectively, this study suggests that combined ICB promotes the differentiation of B cell populations, which is associated with efficient tumor suppression and development of irAEs.

DOI： 10.1007/s00262-023-03505-4

Predicting TERT promoter mutation status using 1H-MR spectroscopy and stretched-exponential model of diffusion-weighted imaging in IDH-wildtype diffuse astrocytic glioma without intense enhancement. 査読国際誌

Koji Yamashita, Ryusuke Hatae, Kazufumi Kikuchi, Daisuke Kuga, Nobuhiro Hata, Hidetaka Yamamoto, Makoto Obara, Koji Yoshimoto, Kousei Ishigami, Osamu Togao

Neuroradiology 65 ( 8 ) 1205 - 1213 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Isocitrate dehydrogenase (IDH)-wildtype diffuse astrocytic glioma with telomerase reverse transcriptase (TERT) promoter mutation is defined as glioblastoma by the WHO 2021 criteria, revealing that TERT promotor mutation is highly associated with tumor aggressiveness. The aim of this study was to identify features from MR spectroscopy (MRS) and multi-exponential models of DWI distinguishing wild-type TERT (TERTw) from TERT promoter mutation (TERTm) in IDH-wildtype diffuse astrocytic glioma. METHODS: Participants comprised 25 adult patients with IDH-wildtype diffuse astrocytic glioma. Participants were classified into TERTw and TERTm groups. Point-resolved spectroscopy sequences were used for MRS data acquisition. DWI was performed with 13 different b-factors. Peak height ratios of NAA/Cr and Cho/Cr were calculated from MRS data. Mean apparent diffusion coefficient (ADC), perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), distributed diffusion coefficient (DDC), and heterogeneity index (α) were obtained using multi-exponential models from DWI data. Each parameter was compared between TERTw and TERTm using the Mann-Whitney U test. Correlations between parameters derived from MRS and DWI were also evaluated. RESULTS: NAA/Cr and Cho/Cr were both higher for TERTw than for TERTm. The α of TERTw was smaller than that of TERTm, while the f of TERTw was higher than that of TERTm. NAA/Cr correlated negatively with α, but not with other DWI parameters. Cho/Cr did not show significant correlations with any DWI parameters. CONCLUSION: The combination of NAA/Cr and α may have merit in clinical situation to predict the TERT mutation status of IDH-wildtype diffuse astrocytic glioma without intense enhancement.

DOI： 10.1007/s00234-023-03177-y

Evaluation of appropriate conditions for Oncomine DxTT testing of FFPE specimens for driver gene alterations in non-small cell lung cancer. 査読国際誌

Eiji Iwama, Hidetaka Yamamoto, Fumihiko Okubo, Kayo Ijichi, Ritsu Ibusuki, Yoshimasa Shiaraishi, Yasuto Yoneshima, Kentaro Tanaka, Yoshinao Oda, Isamu Okamoto

Thoracic cancer 14 ( 23 ) 2288 - 2296 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The Oncomine Dx Target Test Multi-CDx System (ODxTT) is a next-generation sequencing panel approved as a companion diagnostic for drugs targeted to corresponding gene alterations in non-small cell lung cancer. However, appropriate slide conditions for ODxTT have remained unclear. METHODS: We focused on the production of the number of tumor cells on a formalin-fixed paraffin-embedded (FFPE) section and the number of prepared slides, designated the TS value, and determined a TS value of ≥4000 as a target slide condition for ODxTT. We evaluated the impact of this condition on ODxTT testing with tumor specimens found to have a TS of <4000 (n = 23) or a TS of ≥4000 (n = 142). RESULTS: A positive correlation was apparent between the TS value and the concentrations of both DNA and RNA. Among the 142 samples with a TS of ≥4000, a sufficient concentration of DNA or RNA for ODxTT analysis was achieved in 100% and 98% samples, respectively. Among samples explored for driver gene alterations after determination of the target slide condition (TS ≥4000), most (84.9%) had a TS of ≥4000 and were submitted for ODxTT analysis. CONCLUSION: Our findings indicate that a TS of ≥4000 is a feasible and relevant criterion for ODxTT testing, and its adoption should help to improve the success rate of such testing in clinical practice.

DOI： 10.1111/1759-7714.15014

Prognostic scores for patients with salivary adenoid cystic carcinoma without lymph node metastasis. 査読国際誌

Hikari Shimoda, Masanori Teshima, Takayuki Murase, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Ken-Ichi Taguchi, Hidetaka Yamamoto, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Daisuke Kawakita, Kazuo Sakurai, Nobuhiro Hanai, Toru Nagao, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Hiroshi Inagaki

Oral oncology 145 106491 - 106491 2023年7月

記述言語：英語

Adenoid cystic carcinoma (AdCC) of salivary gland grows relatively slowly, but occasionally develops distant metastasis. Although cervical lymph node metastasis (LNM) has been reported as a strong prognostic factor, most of AdCC do not have LNM. In this study, we investigated the prognostic factors to predict disease free survival (DFS), distant metastasis free survival (DMFS), and overall survival (OS) for 175 patients surgically treated for AdCC without LNM, and developed prognostic score (PS) determined as number of positive prognostic factors. The following emerged as significant prognostic factors: positive surgical margin in DFS, pT3/4 and positive surgical margin in DMFS, and positive surgical margin and high-histological grade in OS. 10-year DFS rates were 56.4% in PS0, and 19.1% in PS1 (p < 0.0001). 10-year DMFS rates were 86.3% in PS0, 56.4% in PS1, and 30.7% in PS2 (p < 0.0001). 10-year OS rates were 100% in PS0, 73.3% in PS1, and 38.8% in PS2 (p < 0.0001).

DOI： 10.1016/j.oraloncology.2023.106491

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma. 査読国際誌

Kaori Ueda, Takayuki Murase, Daisuke Kawakita, Toshitaka Nagao, Kimihide Kusafuka, Masato Nakaguro, Makoto Urano, Hidetaka Yamamoto, Ken-Ichi Taguchi, Satoshi Kano, Yuichiro Tada, Kiyoaki Tsukahara, Kenji Okami, Tetsuro Onitsuka, Yasushi Fujimoto, Kazuo Sakurai, Nobuhiro Hanai, Toru Nagao, Ryo Kawata, Naohito Hato, Ken-Ichi Nibu, Hiroshi Inagaki

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 36 ( 10 ) 100274 - 100274 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

DOI： 10.1016/j.modpat.2023.100274

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study 査読

Ryosuke Otsuji, Nobuhiro Hata, Yusuke Funakoshi, Daisuke Kuga, Osamu Togao, Ryusuke Hatae, Yuhei Sangatsuda, Yutaka Fujioka, Kosuke Takigawa, Aki Sako, Kazufumi Kikuchi, Tadamasa Yoshitake, Hidetaka Yamamoto, Masahiro Mizoguchi, Koji Yoshimoto

NEUROLOGIA MEDICO-CHIRURGICA 63 ( 8 ) 364 - 374 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN NEUROSURGICAL SOC

We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of pa-tients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre-and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger co-horts.

DOI： 10.2176/jns-nmc.2022-0351

The T2-FLAIR mismatch sign in glioblastoma, isocitrate dehydrogenase wild-type A case report. 査読国際誌

Shunsuke Nishimura, Koji Yamashita, Osamu Togao, Kazufumi Kikuchi, Daisuke Kuga, Hidetaka Yamamoto, Koji Yoshimoto, Kousei Ishigami

Acta radiologica open 12 ( 6 ) 20584601231184565 - 20584601231184565 2023年6月

記述言語：英語

We present a case of the T2-FLAIR mismatch sign in glioblastoma, isocitrate dehydrogenase (IDH)-wild type. The T2-FLAIR mismatch sign is known as a highly specific imaging finding of astrocytoma, IDH-mutant. Meanwhile, IDH-wildtype diffuse astrocytic gliomas with telomerase reverse transcriptase (TERT) promoter mutation in adults are defined as glioblastoma in the 2021 World Health Organization Classification of Tumors of the Central Nervous System, fifth edition (2021 WHO classification), which underscores the importance of molecular information in central nervous system tumors. This indicates even glioblastoma, IDH-wild type may be masquerading as lower-grade glioma in histology. The reasons for the discrepancy between tumors with less aggressive histology and poor prognosis caused by telomerase reverse transcriptase promoter mutation of IDH-wildtype diffuse glioma remain unclear. However, glioblastoma, IDH-wildtype should be considered as a potential differential diagnosis even in patients with the T2-FLAIR mismatch sign in diffuse gliomas.

DOI： 10.1177/20584601231184565

Prognostic implications of the immunohistochemical expression of perilipin 1 and adipophilin in high-grade liposarcoma. 査読国際誌

Kengo Kawaguchi, Kenichi Kohashi, Taro Mori, Hidetaka Yamamoto, Takeshi Iwasaki, Izumi Kinoshita, Yosuke Susuki, Hiroshi Furukawa, Makoto Endo, Yoshihiro Matsumoto, Yasuharu Nakashima, Yoshinao Oda

Journal of clinical pathology 2023年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma. METHODS: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS. RESULTS: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively). CONCLUSIONS: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

DOI： 10.1136/jcp-2023-208814

Gastric cancer in Lynch syndrome observed by image-enhanced endoscopy. 査読国際誌

Keisuke Kawasaki, Shinichiro Kawatoko, Chiaki To, Hidetaka Yamamoto, Takehiro Torisu

Gastrointestinal endoscopy 98 ( 2 ) 259 - 260 2023年5月

TRK-inhibitor control of an NTRK-rearranged spindle cell tumor with malignant transformation in an adolescent. 査読国際誌

Naoko Higuchi, Yuko Honda, Yuhki Koga, Hiroshi Asai, Hiroaki Ono, Wakako Kato, Kentaro Nakashima, Esther De La Cuesta, Toshiaki Tsujino, Hidetaka Yamamoto, Koichi Kusuhara, Masanori Hisaoka, Shouichi Ohga

Pediatric blood & cancer e30379 2023年5月

Amide proton transfer (APT) imaging of breast cancers and its correlation with biological status. 査読国際誌

Takeshi Kamitani, Koji Sagiyama, Yuzo Yamasaki, Takuya Hino, Tatsuhiro Wada, Makoto Kubo, Sayuri Akiyoshi, Hidetaka Yamamoto, Hidetake Yabuuchi, Kousei Ishigami

Clinical imaging 96 38 - 43 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To assess the usefulness of amide proton transfer (APT) imaging to predict the biological status of breast cancers. METHOD: Sixty-six patients (age range 31-85 years, mean 58.9 years) with histopathologically proven invasive ductal carcinomas of 2 cm or larger in diameter were included in this study. 3D APT weighted imaging was conducted on a 3 T scanner. Mean APT signal intensity (SI) was analyzed in relation to biological subtypes, Ki-67 labeling index, and nuclear grades (NGs). RESULTS: The triple-negative (TN) cancers (n = 10; 2.75 ± 0.42%) showed significantly higher APT SI than the luminal type cancers (n = 48; 1.74 ± 0.83) and HER2 cancers (n = 8; 1.83 ± 0.21) (P = 0.0007, 0.03). APT SI had weakly positive correlation with the Ki-67 labeling index (r = 0.38, P = 0.002). The mean APT SIs were significantly higher for high-Ki-67 (>30%) (n = 31; 2.25 ± 0.70) than low-Ki-67 (≤30%) cancers (n = 35; 1.60 ± 0.79) (P = 0.0007). There was no significant difference in the APT SIs between NG 1-2 (n = 31; 1.71 ± 0.84) and NG 3 (n = 35; 2.08 ± 0.76%) cancers (P = 0.06). CONCLUSIONS: TN and high-Ki-67 breast cancers showed high APT SIs. APT imaging can help to predict the biological status of breast cancers.

DOI： 10.1016/j.clinimag.2023.02.002

High-risk HPV-related squamous cell carcinoma in the temporal bone: a rare but noteworthy subtype. 国際誌

Takahiro Hongo, Hidetaka Yamamoto, Ryosuke Kuga, Noritaka Komune, Masaru Miyazaki, Nana Akagi Tsuchihashi, Teppei Noda, Nozomu Matsumoto, Yoshinao Oda, Takashi Nakagawa

Virchows Archiv : an international journal of pathology 482 ( 3 ) 539 - 550 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

High-risk human papillomavirus (HPV) is a risk factor for the development of several head and neck squamous cell carcinomas (SCCs). However, there have been few reports of high-risk HPV infection in temporal bone squamous cell carcinomas (TBSCCs), and thus the prevalence and clinicopathologic significance of high-risk HPV in TBSCCs are still unclear. We retrospectively collected 131 TBSCCs and analyzed them for transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization; we also assessed the utility of p16-immunohistochemistry (IHC) and Rb-IHC to predict HPV infection. Eighteen (13.7%) of the 131 TBSCCs were positive for p16-IHC, and five of them were positive for high-risk HPV infection (the estimated high-risk HPV positivity rate was 3.8% [5/131]). Interestingly, all five HPV-positive patients were male and had TBSCC on the right side. In the p16-IHC+/HPV+ cases (n = 5), the Rb-IHC showed a partial loss pattern (n = 4) or complete loss pattern (n = 1). In contrast, all p16-IHC-negative cases (n = 113) showed an Rb-IHC preserved pattern. The positive predictive value (PPV) of p16-IHC positivity for high-risk HPV infection was low at 27.8%, while the combination of p16-IHC+/Rb-IHC partial loss pattern showed excellent reliability with a PPV of 100%. The prognostic significance of high-risk HPV infection remained unclear. High-risk HPV-related TBSCC is an extremely rare but noteworthy subtype.

DOI： 10.1007/s00428-023-03497-7

Evaluation of the one-step nucleic acid amplification assay for detecting lymph node metastasis in patients with cervical and endometrial cancer: A multicenter prospective study. 国際誌

Shinichi Togami, Akihide Tanimoto, Shintaro Yanazume, Hideki Tokunaga, Tomoyuki Nagai, Mika Watanabe, Hideaki Yahata, Kazuo Asanoma, Hidetaka Yamamoto, Tomohito Tanaka, Masahide Ohmichi, Takashi Yamada, Yukiharu Todo, Ryutaro Yamada, Hidenori Kato, Wataru Yamagami, Kenta Masuda, Miho Kawaida, Hitoshi Niikura, Takuya Moriya, Hiroaki Kobayashi

Gynecologic oncology 170 70 - 76 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-μm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.

DOI： 10.1016/j.ygyno.2022.12.016

Virtual monochromatic spectral CT imaging in preoperative evaluations for intraductal spread of breast cancer: comparison with conventional CT and MRI.

Yuko Matsuura, Takeshi Kamitani, Koji Sagiyama, Yuzo Yamasaki, Takuya Hino, Makoto Kubo, Hideki Ijichi, Hidetaka Yamamoto, Hidetake Yabuuchi, Kousei Ishigami

Japanese journal of radiology 41 ( 7 ) 733 - 740 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: To investigate the efficacy of virtual monochromatic spectral computed tomography imaging (VMI) in the preoperative evaluation for intraductal spread of breast cancer. MATERIALS AND METHODS: Twenty-four women who underwent spectral CT and were pathologically diagnosed with ductal carcinoma with a ≥ 2-cm noninvasive component were retrospectively enrolled in Group 1. Twenty-two women with 22 lesions pathologically diagnosed with ductal carcinoma in situ or microinvasive carcinoma were enrolled in Group 2. We compared the contrast-to-noise ratios (CNRs) of the lesions on conventional 120-kVp CT images and 40-keV VMIs in Group 1. Two board-certified radiologists measured the maximum diameters of enhancing areas on 120-kVp CT, 40-keV VMI, and MRI in Group 2 and compared with histopathological sizes. RESULTS: The quantitative assessment of Group 1 revealed that the mean ± SD of the CNRs in the 40-keV images were significantly greater than those in the 120-kVp images (5.5 ± 1.9 vs. 3.6 ± 1.5, p < 0.0001). The quantitative assessment of Group 2 demonstrated that the lesion size observed in the conventional 120-kVp CT images by both readers was significantly underestimated as compared to the histopathological size (p = 0.017, 0.048), whereas both readers identified no significant differences between the lesion size measured on 40-keV VMI and the histopathological data. In a comparison with MRI, 40-keV VMI provided measurement within a 10-mm error range in more lesions as compared to the conventional 120-kVp CT. CONCLUSION: VMI improves the evaluation of intraductal spread and is useful for the preoperative evaluations of breast cancer.

DOI： 10.1007/s11604-023-01392-4

The Expression of Insulin-Like Growth Factor II Messenger RNA-Binding Protein 3 Upregulated in Intradural Extramedullary Schwannomas.

Hirofumi Bekki, Yoshihiro Matsumoto, Masato Yoshimoto, Shin Ishihara, Kenichi Kawaguchi, Hidetaka Yamamoto, Yoshinao Oda, Yasuharu Nakashima, Katsumi Harimaya

Spine surgery and related research 7 ( 1 ) 36 - 41 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Tumor size is an important factor in determining the appropriate clinical management of intradural-extramedullary schwannoma. A tumor volume reduction may be achieved by conservative targeted therapy instead of invasive surgery if a molecular event related to tumor size is discovered. Insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an oncofetal tumor-associated antigen that is expected to be a target for immunotherapy, was focused on in this study. METHODS: The IMP3 status was assessed by immunohistochemistry in 64 samples of intradural-extramedullary schwannoma, and the correlation between IMP3 expression and tumor size was evaluated. RESULTS: Immunohistochemically, high IMP3 expression was observed in ～85% of schwannomas. The maximum tumor diameter of the high IMP3 expression group was significantly larger than that of the low IMP3 expression group (34.3 mm vs 18.5 mm, p=0.002). The receiver operating characteristic curve demonstrated that a maximum tumor diameter of 24 mm was a predictable factor for IMP3 expression (sensitivity, 0.7; 1-specificity, 0.2; area under the curve, 0.82). CONCLUSIONS: Upregulated IMP3 expression was associated with large tumor size, suggesting a possible therapeutic approach.

DOI： 10.22603/ssrr.2022-0063

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