Faculty Profiles - FUJIWARA Toshiyoshi

Papers - FUJIWARA Toshiyoshi

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高齢がん患者に対するがん診療高齢大腸癌患者における主観的包括的栄養評価(SGA)の有用性単施設前向き観察研究

寺石文則, 吉田有佑, 庄司良平, 松三雄騎, 重安邦俊, 近藤喜太, 香川俊輔, 田村利枝, 松岡義和, 藤原俊義

日本癌治療学会学術集会抄録集 62回 CCWS1 - 6 2024.10

Robot-Assisted Pancreaticoduodenectomy Using the Anterior Superior Mesenteric Artery-First Approach for Pancreatic Cancer. International journal

Kosei Takagi, Tomokazu Fuji, Kazuya Yasui, Motohiko Yamada, Takeyoshi Nishiyama, Yasuo Nagai, Noriyuki Kanehira, Toshiyoshi Fujiwara

Annals of surgical oncology 2024.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The superior mesenteric artery (SMA)-first approach for pancreatic cancer (PC) is common surgical technique in pancreaticoduodenectomy. To date, few studies have reported SMA-first approach in robot-assisted pancreaticoduodenectomy (RPD). Herein, we present the anterior SMA-first approach for PC during RPD. PATIENT AND METHOD: A 75-year-old man with resectable PC underwent RPD after neoadjuvant chemotherapy. As pancreatic head tumor contacted with the superior mesenteric vein (SMV), the anterior SMA approach was applied. After the mesenteric Kocher maneuver, the jejunum was divided and the left side of the SMA was dissected. Subsequently, the anterior plane of the SMA was dissected. Following the division of branches from the mesenteric vessels, the SMA was taped, and the circumferential dissection around the SMA was performed to detach the pancreatic neck from the SMA completely. Finally, the dissection between the SMV and the tumor was performed under vascular control to remove the specimen. CONCLUSIONS: The anterior SMA-first approach can be optional in patients with PC undergoing RPD. This unique approach allows for the circumferential dissection around the SMA during RPD.

DOI： 10.1245/s10434-024-16305-6

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The Liver Transection Area Is a Novel Predictor for Surgical Difficulty in Laparoscopic Liver Resection. International journal

Motohiko Yamada, Kosei Takagi, Tomokazu Fuji, Kazuya Yasui, Jiro Kimura, Takeyoshi Nishiyama, Yasuo Nagai, Noriyuki Kanehira, Toshiyoshi Fujiwara

Journal of clinical medicine 13 ( 19 ) 2024.9

Language：English Publishing type：Research paper (scientific journal)

Background: A difficulty scoring system was developed to estimate the surgical outcomes of laparoscopic liver surgery (LLS); however, the effect of the liver transection area (LTA) on LLS outcomes have not been previously examined. Therefore, this study investigated the predictive significance of the LTA for LLS. Methods: This retrospective study included 106 patients who underwent LLS in our hospital between January 2012 and December 2023. The association of the LTA with the surgical difficulty level and operative time was investigated. Multivariate analyses were performed to identify factors predicting surgical difficulty in LLS. Results: The median LTA and operative time were 62.5 (IQR, 36.0-91.8) cm2 and 250 (IQR, 195-310) minutes, respectively. The LTA was significantly associated with surgical difficulty as evaluated using the IWATE Criteria. Moreover, the LTA significantly correlated with operative time (r2 = 0.19, p < 0.001). The multivariable analyses found that the LTA (≥59 cm2) (odds ratio [OR], 6.07; 95% confidence interval [CI], 2.38-16.6; p < 0.001) and the type of LLS (≥segmentectomy) (OR, 3.79; 95% CI, 1.35-11.4; p = 0.01) were significant factors associated with surgical difficulty. Conclusions: The LTA is a useful parameter that reflects the difficulty of LLS.

DOI： 10.3390/jcm13195686

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p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. Reviewed International journal

Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Molecular therapy. Oncology 32 ( 3 ) 200845 - 200845 2024.9

Language：English Publishing type：Research paper (scientific journal)

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

DOI： 10.1016/j.omton.2024.200845

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Central pancreatectomy of the remnant pancreas without reconstruction after pancreatoduodenectomy. International journal

Kinji Hirono, Kosei Takagi, Motohiko Yamada, Jiro Kimura, Tomokazu Fuji, Kazuya Yasui, Takeyoshi Nishiyama, Yasuo Nagai, Noriyuki Kanehira, Toshiyoshi Fujiwara

Surgical case reports 10 ( 1 ) 214 - 214 2024.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: There are several reports on the safety and feasibility of pancreatoduodenectomy (PD) without reconstruction of the small remnant pancreas. However, a few studies have explored central pancreatectomy (CP) for non-reconstructed small remnant pancreases after PD. This study presents a case of CP without pancreatic reconstruction after PD. CASE PRESENTATION: A 58-year-old man with cerebral palsy underwent PD for distal cholangiocarcinoma. Three years postoperatively, a 12-mm tumor was detected in the remnant pancreatic body and diagnosed as a pancreatic neuroendocrine neoplasm. Surgical resection was performed, because the tumor was enlarged and chemotherapy resistant. The afferent loop with pancreatojejunostomy anastomosis was dissected, and CP, including pancreatojejunostomy anastomosis, was performed. Given the remnant pancreas was hard and atrophic, the pancreatic tail was transected using a stapler without reconstructing the small remnant pancreas. The patient experienced no postoperative complications including postoperative pancreatic fistula, and the endocrine function of the pancreas was preserved. CONCLUSIONS: We present a case of remnant pancreatic CP that did not require reconstruction after PD. Preservation of the small remnant pancreas without reconstruction during CP may be feasible to maintain endocrine function in select patients after PD.

DOI： 10.1186/s40792-024-02018-1

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Ramucirumab in second‑line advanced colorectal cancer therapy: A study on therapeutic outcomes and hepatic sinusoidal platelet aggregation. Reviewed International journal

Keisuke Kimura, Yosuke Katata, Yuzo Umeda, Takehiro Tanaka, Shuya Yano, Kazuhiro Yoshida, Toshiyoshi Fujiwara, Yoshiko Mori, Takeshi Yamada, Takeshi Nagasaka

Oncology letters 28 ( 3 ) 439 - 439 2024.9

Language：English Publishing type：Research paper (scientific journal)

The present study investigated the role of ramucirumab (RAM) in treating liver metastases (LMs) as a second-line or salvage treatment in patients with advanced CRC. Of the 36 patients, 21 (58%) received RAM plus folinic acid, fluorouracil and irinotecan (FOLFIRI) as second-line treatment, whereas 15 (42%) received it in a salvage setting. The median overall survival time was 23 months [95% confidence interval (CI), 12-34 months] for those in the second-line treatment group and 8 months (95% CI, 5-19 months) for those in the salvage treatment group. Of the 36 patients, 14 (39%) underwent surgical resection of LMs during chemotherapy. A total of 6 patients underwent surgical resection for LMs for the first time during second-line RAM plus FOLFIRI (RAM-LM); of the remaining 8 patients, 6 underwent resection of LMs during first-line bevacizumab (BEV)-based chemotherapy (BEV-LM). Immunohistochemical analysis of CD42b showed that the platelet aggregation score (CD42b score), which ranges from 0 (absence of deposition) to 3 (presence of linear deposition), tended to decrease with the increasing duration of treatment with both RAM and BEV. Although there was no significant difference in the mean duration of anti-VEGF antibody treatment between the BEV-LM and RAM-LM groups, the median CD42b score was higher in the RAM-LM group (median CD42b score, 3; range, 0-3) compared with that in the BEV-LM group (median CD42b score, 1; range, 0-3; P=0.01), suggesting that RAM induces a different degree of platelet aggregation in liver sinusoids compared to BEV.

DOI： 10.3892/ol.2024.14572

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間質のコラーゲン産生は胃癌における腫瘍融解ウイルス療法の治療抵抗性を増強する(Stromal collagen type 1 deposition promotes resistance to oncolytic virotherapy in gastric cancer)

大倉友博, 田澤大, 菊地覚次, 黒田新士, 大原利章, 野間和広, 大塚旬子, 大木理恵子, 浦田泰生, 香川俊輔, 藤原俊義, 藤原俊義

日本癌学会総会記事 83回 P - 2252 2024.9

HIF-PHD阻害薬による偽性低酸素はMSS大腸癌の充腫瘍免疫応答を増強する(Pseudohypoxia by HIF-PHD inhibitors activates tumor immune response for MSS colorectal cancer)

大原利章, 陳悦華, 濱田祐輔, 賀島肇, 菊地覚次, 野間和広, 田澤大, 藤澤真義, 藤原俊義, 松川昭博

日本癌学会総会記事 83回 E - 2017 2024.9

【免疫療法のバイオマーカー探索】PD-L1陽性癌関連線維芽細胞の免疫チェックポイント阻害剤のバイオマーカーとしての可能性

河崎健人, 野間和広, 藤原俊義

癌と化学療法 51 ( 9 ) 865 - 868 2024.9

Language：Japanese Publisher：(株)癌と化学療法社

近年は本邦でも食道癌に対する免疫チェックポイント阻害剤(immune checkpoint inhibitors:ICIs)の適応が拡がっており,切除不能進行・再発食道癌に対する一次治療からのICIsの使用が推奨されている。一方で,癌関連線維芽細胞(cancer-associated fibroblasts:CAFs)は癌微小環境を構成する主要な細胞であり,その存在は予後不良因子として報告されている。CAFsは腫瘍促進的な機能を有しており,近年では腫瘍免疫との関連も報告されている。われわれは,食道癌臨床検体においてprogrammed cell death ligand 1(PD-L1)陽性CAFsの存在を確認し,予後不良因子であることを報告した。また,癌細胞とCAFsは互いにPD-L1発現を上昇させ,腫瘍内を免疫抑制状態へ誘導していることを示した。このような癌微小環境下においては,PD-L1陽性CAFsを治療標的とすることで,より効率よく腫瘍縮小効果を期待できる可能性がある。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00296&link_issn=&doc_id=20240920170003&doc_link_id=%2Fab8gtkrc%2F2024%2F005109%2F003%2F0865-0868%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2024%2F005109%2F003%2F0865-0868%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

The state of robotic vs. open pancreatoduodenectomy. International journal

Kosei Takagi, Tomokazu Fuji, Kazuya Yasui, Motohiko Yamada, Takeyoshi Nishiyama, Yasuo Nagai, Noriyuki Kanehira, Toshiyoshi Fujiwara

Gland surgery 13 ( 8 ) 1344 - 1348 2024.8

Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT). Reviewed International journal

Takuya Fujimoto, Osamu Yamasaki, Noriyuki Kanehira, Hirokazu Matsushita, Yoshinori Sakurai, Naoya Kenmotsu, Ryo Mizuta, Natsuko Kondo, Takushi Takata, Mizuki Kitamatsu, Kazuyo Igawa, Atsushi Fujimura, Yoshihiro Otani, Makoto Shirakawa, Kunitoshi Shigeyasu, Fuminori Teraishi, Yosuke Togashi, Minoru Suzuki, Toshiyoshi Fujiwara, Hiroyuki Michiue

Cancer science 2024.8

Language：English Publishing type：Research paper (scientific journal)

Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.

DOI： 10.1111/cas.16298

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Comprehensive geriatric assessment as an indicator of postoperative recovery in older patients with colorectal cancer. Reviewed International journal

Fuminori Teraishi, Ryohei Shoji, Yoshitaka Kondo, Shunsuke Kagawa, Rie Tamura, Yoshikazu Matsuoka, Hiroshi Morimatsu, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

Journal of geriatric oncology 101837 - 101837 2024.7

Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody. Reviewed International journal

Teruki Kobayashi, Kazuhiro Noma, Seitaro Nishimura, Takuya Kato, Noriyuki Nishiwaki, Toshiaki Ohara, Tomoyoshi Kunitomo, Kento Kawasaki, Masaaki Akai, Satoshi Komoto, Hajime Kashima, Satoru Kikuchi, Hiroshi Tazawa, Yasuhiro Shirakawa, Peter L Choyke, Hisataka Kobayashi, Toshiyoshi Fujiwara

Molecular cancer therapeutics 23 ( 7 ) 1031 - 1042 2024.7

Language：English Publishing type：Research paper (scientific journal)

Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line-derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.

DOI： 10.1158/1535-7163.MCT-23-0527

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BRAF-mutant microsatellite-stable rectal cancer with acquired KRAS mutation leading to drug resistance in liver metastasis. Reviewed International journal

Kunitoshi Shigeyasu, Hideki Yamamoto, Toshiaki Takahashi, Kazuya Moriwake, Masashi Kayano, Sho Takeda, Yuki Matsumi, Yuzo Umeda, Yoshitaka Kondo, Fuminori Teraishi, Kazuya Yasui, Tomokazu Fuji, Shunsuke Kagawa, Toshiyoshi Fujiwara

International cancer conference journal 13 ( 3 ) 189 - 192 2024.7

Language：English Publishing type：Research paper (scientific journal)

BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.

DOI： 10.1007/s13691-024-00678-2

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Rare case of rectal carcinoid with synchronous primary carcinoid tumors of the lung misdiagnosed as lung metastases. Reviewed International journal

Fuminori Teraishi, Rhohei Shoji, Toshiyoshi Fujiwara

JGH open : an open access journal of gastroenterology and hepatology 8 ( 7 ) e70003 2024.7

Language：English Publishing type：Research paper (scientific journal)

A 68-year-old woman was referred to our hospital for rectal surgery after a pathological diagnosis of rectal carcinoid with venous invasion following endoscopic submucosal dissection of a 5 mm-sized submucosal tumor in the lower rectum. Chest CT showed nodules in the left upper lobe and right lower lobe, but positron emission tomography and somatostatin receptor scintigraphy showed no hyperaccumulation in the lung nodules. CT-guided needle biopsy was performed on the nodular lesion in the left upper lobe, which showed focal growth of tumor cells with a high N/C ratio and positive synaptophysin, leading to a diagnosis of pulmonary metastasis of rectal carcinoid. Since the patient was asymptomatic and did not wish to undergo surgery or chemotherapy, she was followed up strictly with sufficient informed consent. Three years have passed since the diagnosis, and there is no tendency for the lung metastasis to increase, and no other new lesions have been observed. The disease had not progressed and remained stable. Therefore, immunohistological analysis of the lung biopsy specimen was performed again, which was positive for TTF-1 and negative for CDX2. Consequently, the diagnosis was changed to primary lung carcinoid tumors, and the patient remains under follow-up with no disease progression.

DOI： 10.1002/jgh3.70003

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下部消化管新規内科治療が台頭する時代の炎症性腸疾患に対する外科治療の意義手術適応クローン病患者において術前の栄養学的・免疫学的指標の改善が術後合併症を軽減する

Moriwake Kazuya, Kondo Yoshitaka, Sakamoto Masaki, Kanaya Nobuhiko, Kakiuchi Yoshihiko, Shigeyasu Kunitoshi, Kuroda Shinji, Teraishi Fuminori, Kagawa Shunsuke, Fujiwara Toshiyoshi

日本消化器外科学会総会 79回 345 - 345 2024.7

当院におけるMSI-high大腸癌に対するPembrolizumabの使用経験

松三雄騎, 重安邦俊, 庄司良平, 近藤喜太, 寺石文則, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 2231 - 2231 2024.7

下部消化管大腸癌集学的治療について高齢化社会における大腸癌患者の長期生存を目指した遠隔転移制御戦略

重安邦俊, 高橋利明, 楳田祐三, 垣内慶彦, 松三雄騎, 近藤喜太, 寺石文則, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 596 - 596 2024.7

若手外科医に対する外科手術教育に対しCadaver Surgical Trainingが果たす役割

近藤喜太, 金谷信彦, 重安邦俊, 前田直見, 田辺俊介, 黒田新士, 野間和広, 寺石文則, 楳田祐三, 藤原俊義

日本消化器外科学会総会 79回 2356 - 2357 2024.7

術前治療後の局所進行直腸癌に対するロボット支援手術の短期～中期治療成績

寺石文則, 庄司良平, 賀島肇, 垣内慶彦, 松三雄騎, 重安邦俊, 近藤喜太, 黒田新士, 香川俊輔, 藤原俊義

日本消化器外科学会総会 79回 2317 - 2317 2024.7

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Papers - FUJIWARA Toshiyoshi