Faculty Profiles - Otsuka Motoyuki

Papers - Otsuka Motoyuki

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Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up. International journal

Ryosuke Sato, Katsuyuki Hotta, Toshio Kubo, Shigeru Horiguchi, Hironari Kato, Kazuyuki Matsumoto, Toshiyuki Kozuki, Heiichiro Udono, Katsuyuki Kiura, Motoyuki Otsuka

Cureus 17 ( 2 ) e79001 2025.2

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

We report a case of poorly differentiated pancreatic cancer that showed an exceptional response to combination therapy with nivolumab and metformin. A 58-year-old man presented with epigastric pain and was diagnosed with locally advanced pancreatic cancer with para-aortic lymph node metastasis. After disease progression following modified FOLFIRINOX therapy (a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin), the patient was enrolled in a phase Ib clinical trial of nivolumab (3 mg/kg biweekly) combined with metformin (750 mg/day). Post-treatment imaging showed marked tumor shrinkage with normalization of the tumor markers. During treatment, the patient was diagnosed with early-stage lung cancer and underwent successful left S1+S2 segmentectomy with temporary suspension of immunotherapy. The therapeutic response of pancreatic cancer has been sustained for seven years, with minimal residual disease. This unprecedented response duration is particularly noteworthy considering his microsatellite stability, which typically predicts a limited response to immune checkpoint inhibition. This case demonstrates an exceptional response to nivolumab and metformin combination therapy in poorly differentiated pancreatic cancer. The remarkable durability of the response suggests the need for further investigation to identify patients most likely to benefit from this therapeutic approach.

DOI： 10.7759/cureus.79001

WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.

Genso Notoya, Takahiro Kishikawa, Kengo Yasugi, Takuma Iwata, Takahiro Seimiya, Koji Miyabayashi, Ryota Takahashi, Keisuke Yamamoto, Hideaki Ijichi, Motoyuki Otsuka, Mitsuhiro Fujishiro

Journal of gastroenterology 2024.12

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

BACKGROUND: The proto-oncogene WWP1 is overexpressed in various cancers and contributes to tumor growth and poor prognosis. Recently, WWP1 inhibition was reported to suppress tumor development and cell proliferation by activating the PTEN function. However, the expression profiles and clinical significance of WWP1 in pancreatic ductal adenocarcinoma (PDAC) tissues remain undetermined. Therefore, this study aimed to evaluate the WWP1 expression in PDAC and investigate the therapeutic potential of WWP1 inhibition. METHODS: Cellular proliferation assays were performed using a doxycycline-inducible shWWP1 expression system. Transcriptome analyses were conducted to identify the altered pathways in WWP1-depleted cells. PTEN ubiquitination by WWP1 was confirmed using immunoprecipitation assays. In vivo xenograft and drug screening assays were performed to evaluate the clinical significance of WWP1 inhibition. RESULTS: WWP1 was significantly upregulated in PDAC tissues and associated with poor prognosis. WWP1 depletion significantly reduced the proliferation of PDAC cell lines, correlating with the suppression of the PI3K-AKT pathway. Mechanistically, as reported in other cancer types, PTEN is a target of WWP1 in PDAC cells. PTEN silencing abrogated the growth-inhibitory effects in WWP1-depleted cells, suggesting that the anti-tumor effects of WWP1 inhibition are mediated through PTEN activation. In vivo xenograft studies confirmed that WWP1 depletion substantially inhibited tumor growth. Moreover, drug screening assays revealed that WWP1 depletion had an additive effect with the PI3K-AKT pathway inhibitors on hindering tumor growth. CONCLUSION: WWP1 inhibition enhances the anti-tumor effects of PI3K-AKT pathway inhibitors through PTEN activation. Thus, WWP1 could be a potential therapeutic target in PDAC.

DOI： 10.1007/s00535-024-02192-x

Analysis of painful situations during unsedated esophagogastroduodenoscopy. International journal

Hiromitsu Kanzaki, Sakiko Kuraoka, Takuya Satomi, Shotaro Okanoue, Kenta Hamada, Yoshiyasu Kono, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada, Motoyuki Otsuka

Endoscopy international open 12 ( 11 ) E1267-E1276 2024.11

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

Background and study aims Although esophagogastroduodenoscopy (EGD) is a widely used technique, the procedure is often associated with discomfort. This study aimed to analyze painful situations, their frequency, and factors associated with patient discomfort during EGD. Patients and methods This prospective observational study included patients scheduled to undergo EGD. Seven endoscopists recruited patients scheduled for EGD screening or surveillance. Each endoscopist enrolled 20 patients, performing 10 EGD procedures using ultraslim endoscopes and 10 with standard-sized endoscopes. Data regarding painful situations and frequency were collected using specialized buttons pressed by the patients during EGD. A survey about overall discomfort was conducted after the procedure. Results We analyzed data from 140 patients. Esophageal insertion and duodenal observation were associated with the highest incidence of pressing the pain button, accounting for 59.3% and 40.7% of the cases, respectively. The factor associated with pressing the pain button during esophageal insertion was endoscopist experience (< 10 years). In contrast, younger age and female sex were the factors associated with pressing the pain button during duodenal observation. In the post-procedure survey, 63.6% of patients reported discomfort. Factors associated with patient discomfort included pressing the pain button during esophageal insertion (odds ratio [OR]: 2.84, P = 0.01) and previous painful EGD experience (OR: 2.41, P = 0.03). Concusions This study provides objective data on painful situations, their frequency, and related factors during EGD. Further research and interventions focusing on pain reduction during endoscopic procedures are warranted. The results of this study will help endoscopists manage painful situations and potentially improve skills.

DOI： 10.1055/a-2401-6804

Efficacy and Safety of Endoscopic Ultrasonography-Guided Ethanol Injections of Small Pancreatic Neuroendocrine Neoplasms: a prospective, multicenter study. International journal

Kazuyuki Matsumoto, Hironari Kato, Takao Itoi, Masayuki Kitano, Kazuo Hara, Masaki Kuwatani, Mamoru Takenaka, Reiko Ashida, Shuntaro Mukai, Nozomi Okuno, Kazumichi Kawakubo, Tatsuhiro Yamazaki, Jun Sakurai, Yuki Nakatsuka, Michihiro Yoshida, Motoyuki Otsuka

Endoscopy 2024.10

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

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS)-guided ethanol injection (EI) has recently been introduced as one of the management strategies for pancreatic neuroendocrine neoplasms (PNENs). However, its role as a surgical alternative is unclear. We evaluated the efficacy and safety of EUS-EI in treating small PNENs through a prospective multicentre study. PATIENTS AND METHODS: Patients with Grade 1 tumours of ≤15 mm confirmed by pathology were included. The primary endpoint assessed efficacy and safety, measuring complete ablation using computed tomography at 1 and 6 months, prevention of adverse events (AEs) within 1 month, severe pancreatic fistula at 1 month, and diabetes mellitus (DM) incidence/worsening at 6 months. The composite endpoint of EUS-EI was compared with that of historical results of a study based on surgical treatment. RESULTS: Twenty-five patients with PNENs, with a median tumour size of 10.1 mm, were treated using EUS-EI. Seventy-six percent of the patients achieved the composite primary endpoint (19/25) (95% confidence interval [CI]=54.9%-90.6%), a proportion significantly higher than that of surgical treatment (P=0.0083). Regarding efficacy, 88% (22/25) of the patients achieved complete ablation at 1 and 6 months (95% CI=68.8%-97.5%). Regarding safety, 96% (24/25) of the patients had no severe AEs within 1 month (95% CI=79.7%-99.9%). No patients had severe pancreatic fistulas at 1 month, and 84% (21/25) of the patients had no incidence or exacerbation, or both, of DM at 6 months (95% CI=63.9%-95.5%). CONCLUSION: EUS-EI is safe and could be a potent treatment option for patients with small PNENs.

DOI： 10.1055/a-2452-4607

増大号炎症性腸疾患2024 主題炎症性腸疾患の内科治療基本治療薬(5-ASA製剤,副腎皮質ステロイド,チオプリン製剤)

平岡佐規子, 石黒美佳子, 豊澤惇希, 青山祐樹, 井川翔子, 竹内桂子, 山崎泰史, 井口俊博, 衣笠秀明, 髙原政宏, 大塚基之, 金谷信彦, 近藤喜太, 田中健大

胃と腸 59 ( 10 ) 1453 - 1461 2024.10

Short- and longer-term learning effects from virtual scale endoscopy videos: a useful tool for colorectal lesion size estimation (with video). International journal

Ryosuke Hirai, Hideaki Kinugasa, Mikako Ishiguro, Junki Toyosawa, Yuki Aoyama, Shoko Igawa, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Seiji Kawano, Sakiko Hiraoka, Motoyuki Otsuka

Gastrointestinal endoscopy 2024.10

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

BACKGROUND AND AIMS: Accurate assessment of colorectal polyp size is crucial for determining treatment and surveillance policies. However, visual estimation of lesion diameter is often inaccurate, making simple and effective educational tools essential. We aimed to evaluate the learning effects of virtual scale endoscopy (VSE). METHODS: Thirty-three endoscopists first watched pre-learning videos for SET1. They then estimated the diameters of 20 lesions and referred to instructional videos with VSE for self-study. Subsequently, they watched the post-learning videos for SET2 and estimated the lesion diameters. The error between the estimated and correct lesion sizes of both sets was compared. To evaluate longer-term learning effects, participants answered SET3 and SET4, which consisted of the same questions as SET2 and SET1, respectively, 2-3 months later without watching the instructional video for SET2. RESULTS: The error in the participants' estimation of the correct lesion diameter improved from SET1 to SET2 (34.7 mm ± 6.6 vs. 30.7 mm ± 7.7; p = 0.048), with a significant learning effect and error improvement specifically among non-experts (35.2 mm ± 5.3 vs. 30 mm ± 6.8; p = 0.028). In the SET3 and SET4, participants' errors indicated that the learning effect was well maintained (SET2 vs. SET3; 30.7 mm ± 7.7 vs. 28.6 mm ± 7.2; p = 0.1, and SET1 and SET4: 34.7 mm ± 6.6 vs. 31.7 mm ± 7.1; p = 0.025). CONCLUSIONS: VSE videos are a valuable learning tool for estimating lesion diameter, particularly for novice endoscopists, both in the short- and longer-term.

DOI： 10.1016/j.gie.2024.10.038

Characteristics of diabetes mellitus patients with nonviral chronic liver disease who developed hepatocellular carcinoma. International journal

Kyo Sasaki, Miwa Kawanaka, Yasuyuki Tomiyama, Akinobu Takaki, Motoyuki Otsuka, Fusao Ikeda, Naoko Yoshioka, Hideaki Kaneto, Jun Wada, Tetsuya Fukuda, Keisuke Hino, Sohji Nishina

Hepatology research : the official journal of the Japan Society of Hepatology 2024.10

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

AIM: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for hepatocellular carcinoma (HCC). However, HCC is often diagnosed at an advanced stage in patients with diabetes because of the lack of the best criteria for surveillance candidates. The aim of this study was to identify risk factors for HCC development in patients with diabetes with nonviral chronic liver disease. METHOD: Three hundred thirty T2DM patients with nonviral chronic liver disease who underwent surveillance for HCC by imaging techniques between 2009 and 2020 were enrolled in this multicenter cross-sectional retrospective study. The clinical and laboratory parameters of patients with and without HCC were compared. RESULTS: Age ≥65 years, alcohol intake, lack of hepatic steatosis, triglyceride level <111 mg/dL, Mac2 binding protein glycosylation isomer (M2BPGi) ≥0.9 cut-off index (COI), α-fetoprotein concentration ≥5 ng/mL, and des-γ-carboxy prothrombin concentration ≥26 mAU/mL were independently associated with HCC development. When stratified by age, only alcohol intake (odds ratio [OR] 114.19, p < 0.001) was associated with HCC development in patients aged <65 years, and medication for diabetes mellitus (OR 5.72, p = 0.001), lack of hepatic steatosis (OR 4.47, p = 0.002), lactate dehydrogenase ≥198 IU/L (OR 2.751, p = 0.031), M2BPGi ≥1.18 COI (OR 9.05, p < 0.001), and FIB-4 index ≥2.59 (OR 3.22, p = 0.017) were associated with HCC development in patients aged ≥65 years. CONCLUSIONS: In addition to age and advanced liver fibrosis, alcohol intake in younger T2DM patients and medication for DM and lack of hepatic steatosis in older T2DM patients should be considered for HCC surveillance by imaging.

DOI： 10.1111/hepr.14124

Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study. International journal

Yuka Obayashi, Shoichiro Hirata, Yoshiyasu Kono, Makoto Abe, Koji Miyahara, Masahiro Nakagawa, Michihiro Ishida, Yasuhiro Choda, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Motoyuki Otsuka

Drugs - real world outcomes 2024.10

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

BACKGROUND AND OBJECTIVE: Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer. METHODS: This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups. RESULTS: Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group. CONCLUSIONS: The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.

DOI： 10.1007/s40801-024-00460-z

Long-term outcomes of endoscopic resection of superficial esophageal squamous cell carcinoma in late-elderly patients. International journal

Katsunori Matsueda, Seiji Kawano, Keisuke Fukui, Shoichiro Hirata, Takuya Satomi, Shoko Inoo, Kenta Hamada, Yoshiyasu Kono, Masaya Iwamuro, Yoshiro Kawahara, Motoyuki Otsuka

Journal of gastroenterology and hepatology 2024.10

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

BACKGROUND AND AIM: As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy. METHODS: Patients aged ≥75 years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS). RESULTS: Two hundred eight consecutive patients were enrolled. The patients' median age was 78 years (range, 75-89 years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6 years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2-84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98-1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16-5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38-5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0-92.9), and 5-year net survival was 1.08 (95% CI, 1.02-1.14). CONCLUSIONS: ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI.

DOI： 10.1111/jgh.16764

Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants. International journal

Shoichiro Hirata, Kenta Hamada, Masaya Iwamuro, Hirokazu Mouri, Koji Miyahara, Takao Tsuzuki, Kenji Yamauchi, Sayo Kobayashi, Sakuma Takahashi, Ryuta Takenaka, Shinichiro Hori, Masafumi Inoue, Tatsuya Toyokawa, Mamoru Nishimura, Shuhei Ishiyama, Jiro Miyaike, Ryo Kato, Minoru Matsubara, Naoko Yunoki, Hiromitsu Kanzaki, Yoshiro Kawahara, Hiroyuki Okada, Hideki Ishikawa, Motoyuki Otsuka

Journal of gastroenterology and hepatology 2024.10

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

BACKGROUND AND AIM: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. METHODS: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. RESULTS: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. CONCLUSIONS: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.

DOI： 10.1111/jgh.16757

Effectiveness of data-augmentation on deep learning in evaluating rapid on-site cytopathology at endoscopic ultrasound-guided fine needle aspiration. International journal

Yuki Fujii, Daisuke Uchida, Ryosuke Sato, Taisuke Obata, Matsumi Akihiro, Kazuya Miyamoto, Kosaku Morimoto, Hiroyuki Terasawa, Tatsuhiro Yamazaki, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hironari Kato, Hirofumi Inoue, Ten Cho, Takayoshi Tanimoto, Akimitsu Ohto, Yoshiro Kawahara, Motoyuki Otsuka

Scientific reports 14 ( 1 ) 22441 - 22441 2024.9

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

Rapid on-site cytopathology evaluation (ROSE) has been considered an effective method to increase the diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA); however, ROSE is unavailable in most institutes worldwide due to the shortage of cytopathologists. To overcome this situation, we created an artificial intelligence (AI)-based system (the ROSE-AI system), which was trained with the augmented data to evaluate the slide images acquired by EUS-FNA. This study aimed to clarify the effects of such data-augmentation on establishing an effective ROSE-AI system by comparing the efficacy of various data-augmentation techniques. The ROSE-AI system was trained with increased data obtained by the various data-augmentation techniques, including geometric transformation, color space transformation, and kernel filtering. By performing five-fold cross-validation, we compared the efficacy of each data-augmentation technique on the increasing diagnostic abilities of the ROSE-AI system. We collected 4059 divided EUS-FNA slide images from 36 patients with pancreatic cancer and nine patients with non-pancreatic cancer. The diagnostic ability of the ROSE-AI system without data augmentation had a sensitivity, specificity, and accuracy of 87.5%, 79.7%, and 83.7%, respectively. While, some data-augmentation techniques decreased diagnostic ability, the ROSE-AI system trained only with the augmented data using the geometric transformation technique had the highest diagnostic accuracy (88.2%). We successfully developed a prototype ROSE-AI system with high diagnostic ability. Each data-augmentation technique may have various compatibilities with AI-mediated diagnostics, and the geometric transformation was the most effective for the ROSE-AI system.

DOI： 10.1038/s41598-024-72312-3

Gastric adenocarcinoma and proximal polyposis of the stomachに対する内視鏡診療の現状と今後の課題

川野誠司, 田中健大, 大塚基之

Gastroenterological Endoscopy 66 ( 9 ) 1663 - 1671 2024.9

Adverse events after different endoscopic resection procedures for small and intermediate-sized colorectal polyps. Reviewed International journal

Junki Toyosawa, Yasushi Yamasaki, Yuki Aoyama, Kensuke Takei, Shoko Igawa, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Hiroyuki Okada, Motoyuki Otsuka

Digestive diseases (Basel, Switzerland) 1 - 9 2024.8

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

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) have been developed recently, in addition to conventional methods, but adverse events of each method have not been fully clarified. We compared outcomes of each method for the appropriate choice. PATIENTS AND METHODS: Patients who underwent CSP, endoscopic mucosal resection (EMR)/hot snare polypectomy (HSP) or UEMR for small and intermediate-sized colorectal polyps between April 2017 and June 2020 were retrospectively examined. The rate of adverse events and recurrences due to each method were determined as main outcomes. Clinical factors related with adverse events were examined. RESULTS: A total of 1,025 patients with 3,163 polyps underwent polypectomy using any of the methods. CSP, EMR/HSP and UEMR were performed for 704 (22.2%), 2,145 (67.8%) and 314 polyps (9.9%), and median size for each method was 4, 6 and 7 mm, respectively. Delayed bleeding for CSP, EMR/HSP and UEMR was 0%, 0.2% and 0.6% (P = 0.15), and perforation was 0%, 0.1% and 0%, respectively (P = 0.62). Recurrence after CSP, EMR/HSP and UEMR was 0.1%, 0.04% and 1.0%, respectively (P < 0.01). Recurrence for UEMR was significantly higher in the early stage of procedure introduction (P = 0.001). Oral anticoagulants were the risk factor for delayed bleeding (P < 0.01, respectively). CONCLUSIONS: There was no significant difference regarding adverse events among each method for small and intermediate-sized polyps, although recurrence rate after UEMR was higher than other methods.

DOI： 10.1159/000540365

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice. Reviewed International journal

Shigeo Shimose, Issei Saeki, Tetsu Tomonari, Takanori Ito, Joji Tani, Yasuto Takeuchi, Naoki Yoshioka, Takehito Naito, Mamiko Takeuchi, Satoru Kakizaki, Takeshi Hatanaka, Kyo Sasaki, Tetsuya Yasunaka, Masahiro Sakata, Hideki Iwamoto, Satoshi Itano, Tomotake Shirono, Norikazu Tanabe, Takafumi Yamamoto, Atsushi Naganuma, Soji Nishina, Motoyuki Otsuka, Hiroki Kawashima, Tetsuji Takayama, Taro Takami, Takumi Kawaguchi

Oncology letters 28 ( 2 ) 397 - 397 2024.8

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

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

DOI： 10.3892/ol.2024.14530

Gastric syphilis displaying multiple annular lesions. Reviewed International journal

Masaya Iwamuro, Takehiro Tanaka, Motoyuki Otsuka

Gastrointestinal endoscopy 100 ( 2 ) 332 - 333 2024.8

【膵・胆道癌の発生・進展メカニズムを探る】胆道癌の薬剤耐性メカニズム

堤康一郎, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 857 - 862 2024.8

Language：Japanese Publisher：医学図書出版(株)

胆道癌の多くは根治切除が難しく,主に抗癌剤や分子標的薬を用いた薬物療法が行われるが,5年生存率は20%程度であり予後不良な疾患である。この一因として,癌細胞が抗腫瘍効果を有する薬剤から逃れて生存を維持しようとする機構,つまり癌の薬剤耐性保有やその獲得があげられる。これまでに胆道癌における七つの薬剤耐性メカニズム(mechanisms of chemoresistance:MOC)が報告されており,これらの複数が相互にまたは独立して関与していることが明らかとなっている。さまざまな遺伝子異常が基盤となって生じる薬剤耐性メカニズムの理解を深めることは,胆道癌に対する新規の治療戦略や治療法開発につながり,個々の患者における予後改善に寄与することが期待される。(著者抄録)

【今推しの肝胆膵研究手法と疾患モデル】新規モデルによる肝胆膵研究胆嚢オルガノイドを用いた新規治療の開発

織田崇志, 堤康一郎, 大塚基之

肝胆膵 89 ( 2 ) 249 - 254 2024.8

【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

寺澤裕之, 堤康一郎, 原田圭, 服部直, 菊池達也, 小幡泰介, 佐藤亮介, 織田崇志, 松三明宏, 宮本和也, 藤井佑樹, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 801 - 806 2024.8

Language：Japanese Publisher：医学図書出版(株)

膵癌は予後不良な難治癌であるが,その一因として薬剤耐性があげられる。薬剤耐性のメカニズムとして,標的治療が難しいKRAS変異の存在やエピジェネティック機構などの遺伝子変異や薬物代謝の変化,転移・浸潤を促進するEMT,膵癌に特徴的な間質成分の多い腫瘍微小環境,さらにnon-coding RNAによる遺伝子発現の調整などがあり,それらが複合的に影響していると考えられている。この複雑な薬剤耐性メカニズムのさらなる解明がその克服において重要である。(著者抄録)

【膵・胆道癌の発生・進展メカニズムを探る】胆道癌の薬剤耐性メカニズム

堤康一郎, 小幡泰介, 織田崇志, 松三明宏, 宮本和也, 寺澤裕之, 藤井佑樹, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 857 - 862 2024.8

Language：Japanese Publisher：医学図書出版(株)

胆道癌の多くは根治切除が難しく,主に抗癌剤や分子標的薬を用いた薬物療法が行われるが,5年生存率は20%程度であり予後不良な疾患である。この一因として,癌細胞が抗腫瘍効果を有する薬剤から逃れて生存を維持しようとする機構,つまり癌の薬剤耐性保有やその獲得があげられる。これまでに胆道癌における七つの薬剤耐性メカニズム(mechanisms of chemoresistance:MOC)が報告されており,これらの複数が相互にまたは独立して関与していることが明らかとなっている。さまざまな遺伝子異常が基盤となって生じる薬剤耐性メカニズムの理解を深めることは,胆道癌に対する新規の治療戦略や治療法開発につながり,個々の患者における予後改善に寄与することが期待される。(著者抄録)

【膵・胆道癌の発生・進展メカニズムを探る】膵癌の薬剤耐性メカニズム

寺澤裕之, 堤康一郎, 原田圭, 服部直, 菊池達也, 小幡泰介, 佐藤亮介, 織田崇志, 松三明宏, 宮本和也, 藤井佑樹, 赤穂宗一郎, 内田大輔, 松本和幸, 堀口繁, 大塚基之

胆と膵 45 ( 8 ) 801 - 806 2024.8

Language：Japanese Publisher：医学図書出版(株)

膵癌は予後不良な難治癌であるが,その一因として薬剤耐性があげられる。薬剤耐性のメカニズムとして,標的治療が難しいKRAS変異の存在やエピジェネティック機構などの遺伝子変異や薬物代謝の変化,転移・浸潤を促進するEMT,膵癌に特徴的な間質成分の多い腫瘍微小環境,さらにnon-coding RNAによる遺伝子発現の調整などがあり,それらが複合的に影響していると考えられている。この複雑な薬剤耐性メカニズムのさらなる解明がその克服において重要である。(著者抄録)

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