Faculty Profiles - YASUI Kazuya

Papers - YASUI Kazuya

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ADAR1-high tumor-associated macrophages induce drug resistance and are therapeutic targets in colorectal cancer. International journal

Hibiki Umeda, Kunitoshi Shigeyasu, Toshiaki Takahashi, Kazuya Moriwake, Yoshitaka Kondo, Kazuhiro Yoshida, Sho Takeda, Shuya Yano, Yuki Matsumi, Hiroyuki Kishimoto, Tomokazu Fuji, Kazuya Yasui, Hideki Yamamoto, Kosei Takagi, Masashi Kayano, Hiroyuki Michiue, Keiichiro Nakamura, Yoshiko Mori, Fuminori Teraishi, Hiroshi Tazawa, Yuzo Umeda, Shunsuke Kagawa, Ajay Goel, Toshiyoshi Fujiwara

Molecular cancer 24 ( 1 ) 116 - 116 2025.4

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

BACKGROUND: Colorectal cancer (CRC) is considered the third most common type of cancer worldwide. Tumor-associated macrophages (TAMs) have been shown to promote drug resistance. Adenosine-to-inosine RNA-editing, as regulated by adenosine deaminase acting on RNA (ADAR), is a process that induces the posttranscriptional modification of critical oncogenes. The aim of this study is to determine whether the signals from cancer cells would induce RNA-editing in macrophages. METHODS: The effects of RNA-editing on phenotypes in macrophages were analyzed using clinical samples and in vitro and in vivo models. RESULTS: The intensity of the RNA-editing enzyme ADAR1 (Adenosine deaminase acting on RNA 1) in cancer and mononuclear cells indicated a strong positive correlation between the nucleus and cytoplasm. The ADAR1-positive mononuclear cells were positive for CD68 and CD163, a marker for M2 macrophages. Cancer cells transport pro-inflammatory cytokines or ADAR1 protein directly to macrophages via the exosomes, promoting RNA-editing in AZIN1 (Antizyme Inhibitor 1) and GLI1 (Glioma-Associated Oncogene Homolog 1) and resulting in M2 macrophage polarization. GLI1 RNA-editing in the macrophages induced by cancer cells promotes the secretion of SPP1, which is supplied to the cancer cells. This activates the NFκB pathway in cancer cells, promoting oxaliplatin resistance. When the JAK inhibitors were administered, oncogenic RNA-editing in the macrophages was suppressed. This altered the macrophage polarization from M2 to M1 and decreased oxaliplatin resistance in cancer cells. CONCLUSIONS: This study revealed that ADAR1-high TAMs are crucial in regulating drug resistance in CRC and that targeting ADAR1 in TAMs could be a promising treatment approach for overcoming drug resistance in CRC.

DOI： 10.1186/s12943-025-02312-y

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Impact of robotic surgery on postoperative pancreatic fistula for high-risk pancreaticojejunostomy after pancreatoduodenectomy. International journal

Tomokazu Fuji, Kosei Takagi, Yuzo Umeda, Kazuya Yasui, Motohiko Yamada, Yasuo Nagai, Toshiyoshi Fujiwara

Digestive surgery 1 - 21 2025.1

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

BACKGROUND: The safety and feasibility of robotic pancreatoduodenectomy (RPD) in high-risk patients with postoperative pancreatic fistula (POPF) have rarely been investigated, although the rate of POPF is lower than in open pancreatoduodenectomy (OPD). This study aimed to examine the impact of robotic surgery on POPF in high-risk patients after pancreatoduodenectomy (PD). METHODS: This retrospective analysis included 204 patients who underwent RPD between January 2018 and June 2023. Of the 204 patients, 126 with high-risk POPF were included. The outcomes of RPD and OPD were compared. Multivariate analyses were conducted to identify risk factors associated with the development of clinically relevant POPF (CR-POPF) after surgery. RESULTS: Of the 126 patients, 50 underwent RPD and 76 underwent OPD. The incidence of CR-POPF was significantly lower in the RPD group than in the OPD group (6.0% vs. 38.2%, P < 0.001). Multivariate analyses identified OPD as an independent risk factor associated with CR-POPF (odds ratio [OR]: 7.87, 95% confidence interval [CI]: 2.11-29.4, P = 0.002). CONCLUSIONS: This study demonstrated the impact of robotic surgery on POPF in high-risk patients after PD. These results suggest that RPD may be significantly associated with a decreased incidence of CR-POPF in high-risk anastomoses.

DOI： 10.1159/000543737

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Hemodynamic Assessment Using SPY Laser Fluorescence Imaging During Pancreatoduodenectomy with Common Hepatic Artery Resection. International journal

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

Annals of surgical oncology 2024.12

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

BACKGROUND: Pancreatectomies combined with arterial resection can be indicated for pancreatic cancer. In a pancreatectomy with arterial resection, intraoperative confirmation of blood flow through reconstructed vessels is crucial. This study highlights the usefulness of SPY laser fluorescence imaging during a pancreatoduodenectomy with common hepatic artery resection (PD-CHAR). PATIENT AND METHODS: A 55-year-old man with borderline resectable pancreatic head cancer underwent a PD-CHAR. After confirming tumor resectability, reconstruction of the CHA to the proper hepatic artery was performed. Subsequently, the superior mesenteric vein was reconstructed. RESULTS: SPY laser fluorescence imaging demonstrated arterial blood perfusion to the liver through the reconstructed hepatic artery, followed by perfusion from the portal vein. The operation lasted 493 min, with an estimated blood loss of 400 mL. The postoperative course was uneventful with good arterial blood flow. CONCLUSION: The SPY Portable Handheld Imager could be valuable for visualizing blood flow in reconstructed vessels and assessing tissue perfusion during a pancreatectomy combined with vascular reconstruction.

DOI： 10.1245/s10434-024-16659-x

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Rare internal hernia following pancreatoduodenectomy: A case report. International journal

Teruyuki Tsujii, Kosei Takagi, Yasuo Nagai, Kazuya Yasui, Tomokazu Fuji, Toshiyoshi Fujiwara

International journal of surgery case reports 126 110673 - 110673 2024.11

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

INTRODUCTION: Pancreatoduodenectomy (PD) is a complex procedure with a high morbidity rate. Internal hernia following PD is a rare but potentially life-threatening complication. Herein, we describe a rare case of internal hernia after PD. PRESENTATION OF CASE: A 76-year-old man who underwent subtotal stomach-preserving PD 7 years ago presented with vomiting and abdominal pain. Abdominal computed tomography revealed an internal hernia. Because conservative treatment failed, surgical intervention was performed. Intraoperative findings revealed efferent loop herniation in the space between the afferent loop near the Braun anastomosis and transverse mesocolon. The hernia was repositioned and the mesenteric defect was closed. DISCUSSION: This is an extremely rare case of an internal hernia that developed 7 years after PD. As conservative management provides a little chance for improvement, precise diagnosis and prompt re-intervention are essential for the management of internal hernia. In this case, the hernial orifice developed in the space between the afferent and efferent loops and the transverse mesocolon. Internal hernia could be a differential diagnosis in patients with ileus after PD. CONCLUSION: This study provided a detailed description of an extremely rare case of internal hernia following PD. Therefore, internal hernias should be considered in patients undergoing PD.

DOI： 10.1016/j.ijscr.2024.110673

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The required experience of open pancreaticoduodenectomy before becoming a specialist in hepatobiliary and pancreatic surgeons: a multicenter, cohort study of 334 open pancreaticoduodenectomies. International journal

Tomokazu Fuji, Yuzo Umeda, Kosei Takagi, Masayoshi Hioki, Ryuichi Yoshida, Yoshikatsu Endo, Kazuya Yasui, Daisuke Nobuoka, Toshiharu Mitsuhashi, Toshiyoshi Fujiwara

BMC surgery 24 ( 1 ) 366 - 366 2024.11

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

BACKGROUND: Open pancreaticoduodenectomy (OPD) is an essential surgical procedure for expert hepato-biliary-pancreatic (HBP) surgeons. However, there is no standard for how many surgeries must be performed by a surgeon in training before they are considered to have enough experience to ensure surgical safety. METHODS: Cumulative Sum (CUSUM) analysis was performed using the surgical data of OPDs performed during the training period of board-certified expert surgeons of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. RESULTS: Fourteen HBP surgeons participated in this study and performed 334 OPDs during their training period. The median (interquartile range) values for operative time, blood loss, and length of hospital stay were 455 (397-519) minutes, 450 (234--716) ml, and 28 (21-38) days, respectively. CUSUM analysis showed inflection points at 20 surgeries performed for operative time. After 20 procedures, operative time was significantly shorter (461 min vs. 425 min, p = 0.021) and blood loss was significantly lower (470 ml vs. 340 ml, p = 0.038). No significant differences between within 20 and after 21 procedures were found in the complication rate (53% vs. 48%, p = 0.424) and rate of in-hospital deaths (1.5% vs.1.4%. p = 0.945). Up to 20 surgeries, PDAC and another malignant tumor had longer operative time than benign/low malignant diseases (486 min vs. 472 min vs. 429 min, p < 0.001), and higher blood loss (500 ml vs. 502 ml vs. 355 ml, p < 0.001). Mortality rate was higher at PDAC cases (5% vs. 0% vs. 0%, p = 0.01). After the 21 procedures, these outcomes were improved and no differences in by primary disease were observed. Multivariable analysis showed that within 20 surgeries were independent risk factors of longer operative time (HR2.6, p = 0.013) and higher blood loss (HR2.0, p = 0.049). CONCLUSIONS: To stabilize the surgical outcome of OPD for malignant disease, at least 20 surgeries should be performed at a certified institution during surgeon training. TRIAL REGISTRATION: Clinical trial number: Not applicable.

DOI： 10.1186/s12893-024-02677-9

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Risk model for predicting failure to rescue after hepatectomy: Cohort study of 1371 consecutive patients. International journal

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

Hepatology research : the official journal of the Japan Society of Hepatology 2024.11

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

AIM: Although hepatectomy is a complex surgical procedure, its incidence among older patients has increased due to global aging. However, few studies have focused on the association between age and failure to rescue (FTR) posthepatectomy. This study aimed to investigate the association between age and FTR and develop a risk model for FTR following hepatectomy. METHODS: We analyzed a total of 1371 consecutive patients who underwent primary hepatectomy between July 2003 and September 2022. The patients were divided into three groups according to their age: young-old (<65 years), pre-old (65-74 years), and old group (≥75 years). Additionally, the associations among age, FTR, and risk factors for FTR were investigated. Subsequently, a risk model was developed to predict the FTR. RESULTS: Of the 1371 patients, 373 (27.2%) experienced major complications, and FTR occurred in 15 patients. The older group showed a higher FTR rate (8.4%) than the young-old (1.3%) and pre-old (4.3%) groups (p = 0.03). Multivariate analyses indicated that older age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.00-1.15; p = 0.045) and American Society of Anesthesiologists Physical Status score ≥3 (OR 4.35; 95% CI 1.24-15.2; p = 0.02) were independent predictive factors for FTR. The risk model exhibited an accuracy with an area under the curve of 0.80 (95% CI 0.69-0.92). Calibration plots of the model revealed a concordance index of 0.73. CONCLUSIONS: This study identified an association between age, FTR, and risk factors for FTR posthepatectomy. Together, our risk model is a clinically relevant, internally validated, and useful tool for predicting FTR posthepatectomy.

DOI： 10.1111/hepr.14134

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RNA編集酵素ADAR1に基づく大腸癌肝転移の残肝再発リスク層別化の検討

高橋利明, 重安邦俊, 中村峻輔, 高橋政史, 萱野真史, 新田薫, 森分和也, 安井和也, 松三雄騎, 藤智和, 近藤喜太, 寺石文則, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 P80 - 2 2024.10

膵癌の更なる早期発見、早期診断に向けて Ct-DNA内KRAS mutation profileとCA19-9値による膵癌予後予測診断と治療戦略

安井和也, 吉田龍一, 宮本耕吉, 重安邦俊, 高木弘誠, 藤智和, 黒田新士, 藤原俊義

日本癌治療学会学術集会抄録集 62回 OSY9 - 4 2024.10

RNA編集酵素ADAR1に基づく大腸癌肝転移の残肝再発リスク層別化の検討

高橋利明, 重安邦俊, 中村峻輔, 高橋政史, 萱野真史, 新田薫, 森分和也, 安井和也, 松三雄騎, 藤智和, 近藤喜太, 寺石文則, 田澤大, 藤原俊義

日本癌治療学会学術集会抄録集 62回 P80 - 2 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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Central pancreatectomy of the remnant pancreas without reconstruction after pancreatoduodenectomy. Reviewed 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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切除不能大腸癌肝転移に対する肝移植における至適適応の検討

藤智和, 高木弘誠, 安井和也, 西山岳芳, 山田元彦, 永井康雄, 金平典之, 藤原俊儀

移植 59 ( 総会臨時 ) 269 - 269 2024.9

The state of robotic vs. open pancreatoduodenectomy. Reviewed 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

Usefulness of robotic-arm hopping technique in robotic left hemihepatectomy. Reviewed International journal

Kosei Takagi, Kazuya Yasui, Tomokazu Fuji

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 28 ( 7 ) 1214 - 1217 2024.7

伊藤孝司, 清水誠一, 澤田雄, 眞田幸弘, 安井和也, 大平真裕, 長谷川康, 中沼伸一, 蔵満薫, 曽山明彦, 嶋村剛, 小寺由人, 種村彰洋, 小川晃平, 吉住朋晴, 嶋田圭太, 中川健, 江川裕人

移植 59 ( 1 ) 15 - 26 2024.7

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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浸潤性膵管癌に対する膵切除断端の検討

永井康雄, 安井和也, 山田元彦, 木村次郎, 高木弘誠, 藤智和, 黒田新士, 野間和広, 楳田祐三, 藤原俊義

日本消化器外科学会総会 79回 1865 - 1865 2024.7

切除可能膵癌に対する術前化学療法は高齢者に本当に必要か?

安井和也, 永井康雄, 木村次郎, 山田元彦, 高木弘誠, 藤智和, 黒田新士, 野間和広, 楳田祐三, 藤原俊義

日本消化器外科学会総会 79回 1161 - 1161 2024.7

肝胆膵高難度腹腔鏡・ロボット支援下膵頭十二指腸切除術の現状と今後の展望 Two-surgeon techniqueを用いたロボット支援下膵頭十二指腸切除術

藤智和, 高木弘誠, 楳田祐三, 安井和也, 山田元彦, 永井康雄, 黒田新士, 野間和広, 寺石文則, 藤原俊義

日本消化器外科学会総会 79回 466 - 466 2024.7

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Papers - YASUI Kazuya