Faculty Profiles - Otsuka Motoyuki

Papers - Otsuka Motoyuki

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Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer. Reviewed International journal

Tomohiro Kamio, Yoshiyasu Kono, Kensuke Hirosuna, Toshiki Ozato, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Motoyuki Otsuka

Cancer medicine 14 ( 8 ) e70793 2025.4

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

BACKGROUND: Gastric cancer (GC) in younger patients often exhibits aggressive behavior and a poorer prognosis than that in older patients. Although the clinical differences may stem from oncogenic gene variations, it is unclear whether genetic differences exist between these groups. This study compared the genetic profiles of early- and late-onset GC and evaluated their impact on treatment outcomes. METHODS: We analyzed genetic data from 1284 patients with GC in the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, comparing early-onset (≤ 39 years; n = 143) and late-onset (≥ 65 years; n = 1141) groups. The influence of TP53 mutations on the time to treatment failure (TTF) with platinum-based chemotherapy and the sensitivity of cancer cells with different TP53 mutation sites to oxaliplatin were assessed in vitro. RESULTS: Early- and late-onset GC showed distinct genetic profiles, with fewer neoantigen-associated genetic changes observed in early-onset cases. In particular, TP53 has distinct mutation sites; R175H and R273 mutations are more frequent in early- and late-onset GC, respectively. The R175H mutation showed higher sensitivity to oxaliplatin in vitro, consistent with the longer TTF in early-onset patients (17.3 vs. 7.0 months, p = 0.013) when focusing on the patients with TP53 mutations. CONCLUSION: Genomic differences, particularly in TP53 mutation sites, between early- and late-onset GC support the need for age-specific treatment strategies.

DOI： 10.1002/cam4.70793

Microsatellite-high intrahepatic cholangiocarcinoma with favorable treatment outcome using pembrolizumab. Reviewed

Shigeru Horiguchi, Hironari Kato, Kazuya Miyamoto, Kosaku Morimoto, Akihiro Matsumi, Hiroyuki Terasawa, Yuki Fujii, Kazuyuki Matsumoto, Takehiro Tanaka, Motoyuki Otsuka

Clinical journal of gastroenterology 18 ( 2 ) 363 - 368 2025.4

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

Intrahepatic cholangiocarcinoma has a poor prognosis. In unresectable cases, the survival period is short despite combination therapy with cytotoxic anticancer agents and immune checkpoint inhibitors. The usefulness of immune checkpoint inhibitors against malignant tumors with microsatellite instability-high (MSI-H) mutations was shown in the KEYNOTE158 study; however, data for intrahepatic cholangiocarcinoma are insufficient. In the present case, a 65-year-old man with intrahepatic cholangiocarcinoma and lymph node metastasis could not be treated with a combination of gemcitabine, CDDP, and S-1. A comprehensive cancer genomic profiling (CGP) test showed MLH1 pathogenic mutation and MSI-H. When pembrolizumab was administered, the tumor shrinkage effect was rapidly observed, which was sustained even after 30 months. No pathogenic mutations were observed in the germline test, and MSI-high was considered to be due to the MLH1 pathogenic mutation occurring sporadically in somatic cells. MSI-H intrahepatic cholangiocarcinoma is extremely rare. However, because pembrolizumab is expected to be effective, CGP testing should be actively performed.

DOI： 10.1007/s12328-025-02103-4

Endoscopic ultrasonography-guided removal of a stent that had migrated into the pancreas post-pancreaticojejunostomy: A case report. Reviewed International journal

Satoshi Kajitani, Kazuyuki Matsumoto, Kentaro Oki, Akihiro Matsumi, Kazuya Miyamoto, Yuki Fujii, Daisuke Uchida, Koichiro Tsutsumi, Shigeru Horiguchi, Motoyuki Otsuka

DEN open 5 ( 1 ) e70096 2025.4

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

A 64-year-old woman had undergone subtotal stomach-preserving pancreaticoduodenectomy for locally advanced pancreatic head cancer. She had an uneventful postoperative course with no recurrence. However, approximately 18 months after surgery, she presented with recurrent abdominal pain. Although contrast-enhanced computed tomography abdominal radiographs showed internal stent migration to the residual pancreas, dilatation of the tail side of the pancreatic duct was observed. The impaired internal stent was considered to be the cause of the abdominal pain. An attempt to remove the stent via balloon-assisted endoscopy was unsuccessful as the pancreaticojejunostomy site could not be reached. Consequently, endoscopic ultrasonography-guided pancreatic duct drainage was performed, and a plastic stent was placed through the jejunal site to the stomach. Two months later, the endosonographically/endoscopic ultrasonography-guided created route was dilated, and an endoscopic introducer was inserted into the pancreatic duct. Biopsy forceps were advanced through the sheath, allowing the successful removal of the stent by direct grasping. The symptoms of the patient improved, and she was discharged without complications.

DOI： 10.1002/deo2.70096

Endoscopic features of gastric neuroendocrine tumors. Reviewed International journal

Katsunori Matsueda, Noriya Uedo, Masanori Kitamura, Takashi Kanesaka, Muneshin Morita, Satoki Shichijo, Akira Maekawa, Yoji Takeuchi, Koji Higashino, Tomoki Michida, Ryu Ishihara, Seiji Kawano, Motoyuki Otsuka

DEN open 5 ( 1 ) e70088 2025.4

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

OBJECTIVES: The endoscopic features of gastric neuroendocrine tumors (G-NETs) remain unclarified. The present study investigated the endoscopic features of G-NETs in relation to the clinicopathological findings. METHODS: This retrospective study analyzed consecutive patients with G-NETs who received endoscopic or surgical treatment between January 2005 and December 2023. The endoscopic and clinicopathological findings of the lesions were analyzed to provide diagnostic information. RESULTS: Among 29 patients, the characteristic endoscopic findings of G-NETs on white-light images were reddish color (66%), dilated vessels (83%), submucosal tumor-like marginal elevation (59%), and central depression (48%). The gross appearance of G-NETs was classified into two macroscopic subtypes: reddish polypoid lesions (n = 17) and submucosal tumor-like lesions (n = 9). Magnifying narrow-band imaging endoscopy revealed an absent microsurface pattern plus an irregular microvascular pattern in all cases of reddish polypoid lesions with central depressions (100%, 9/9). The findings of a reddish polypoid lesion and an absent microsurface pattern plus an irregular microvascular pattern corresponded to the subepithelial NET component close to the non-neoplastic surface epithelium. Additionally, reddish polypoid lesions were significantly more frequent in type 1 G-NETs than in type 3 G-NETs (80% vs. 11%, p < 0.001), while submucosal tumor-like lesions were significantly more frequent in type 3 G-NETs than in type 1 G-NETs (78% vs. 10%, p < 0.001). CONCLUSIONS: These endoscopic features should increase the index of suspicion and help clinicians to correctly diagnose G-NETs through the pathological examination of biopsy specimens.

DOI： 10.1002/deo2.70088

Efficacy and safety of endoscopic ultrasonography-guided radiofrequency ablation of small pancreatic neuroendocrine neoplasms: A prospective, pilot study. Reviewed International journal

Kazuyuki Matsumoto, Daisuke Uchida, Yasuto Takeuchi, Hironari Kato, Yuki Fujii, Kei Harada, Nao Hattori, Ryosuke Sato, Taisuke Obata, Akihiro Matsumi, Kazuya Miyamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Kazuya Yasui, Ryo Harada, Masakuni Fujii, Motoyuki Otsuka

DEN open 5 ( 1 ) e70073 2025.4

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

OBJECTIVES: Endoscopic ultrasonography (EUS)-guided radiofrequency ablation has recently been introduced as one of the management strategies for small pancreatic neuroendocrine neoplasms (PNENs). However, prospective data on its safety and efficacy remain limited. METHODS: This prospective pilot study was conducted at Okayama University Hospital from May 2023 to December 2024. Patients with grade 1 PNENs ≤15 mm, confirmed by EUS-guided fine-needle aspiration, were included. The primary endpoint was safety (adverse events [AEs] evaluated according to the 2010 guidelines of the American Society for Gastrointestinal Endoscopy. Severe AEs were defined as moderate or higher in American Society for Gastrointestinal Endoscopy grading and grade ≥3. Secondary endpoints included efficacy (complete response on contrast-enhanced computed tomography at 1 and 6 months), treatment details, device failure, diabetes mellitus exacerbation, and overall survival at 6 months. RESULTS: Five patients with non-functional PNENs (median age: 64 years; median tumor size: 10 mm) were treated. AEs occurred in two patients (40%, 2/5), although none was severe. Both patients developed asymptomatic pseudocysts, one experienced mild pancreatitis, and both resolved with conservative treatment. The complete response rates on contrast-enhanced computed tomography at one and 6 months were 100%. The median procedure time was 16 min without any device failure, and the median hospitalization was 5 days. None of the patients developed new-onset or worsening diabetes mellitus. The 6-month overall survival rate was 100%. CONCLUSION: EUS-guided radiofrequency ablation demonstrated a high complete response rate with no severe AEs in this pilot study, suggesting a minimally invasive option for small, low-grade PNENs (jRCTs062230014).

DOI： 10.1002/deo2.70073

A case of pancreatic ductal adenocarcinoma growing within the pancreatic duct mimicking an intraductal tubulopapillary neoplasm. Reviewed

Ryosuke Sato, Kazuyuki Matsumoto, Mayu Uka, Kosei Takagi, Kenji Nishida, Takehiro Tanaka, Yuki Fujii, Koichiro Tsutsumi, Shigeru Horiguchi, Motoyuki Otsuka

Clinical journal of gastroenterology 18 ( 2 ) 376 - 382 2025.4

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

We herein report a case of pancreatic ductal adenocarcinoma (PDAC) that developed within the pancreatic duct and was initially diagnosed as an intraductal tubulopapillary neoplasm (ITPN). A 76-year-old man presented with weight loss and main pancreatic duct dilation. The imaging studies revealed a 30-mm hypovascular tumor within the main duct of the pancreatic head. An endoscopic examination with a biopsy revealed high-grade atypical epithelial cells with immunostaining patterns suggestive of ITPN. Following robot-assisted pancreaticoduodenectomy, postoperative pathology revealed conflicting features: nodular/cribriform infiltrations typical of ITPN and non-lobular replacement with scattered infiltrations characteristic of PDAC. A comprehensive genomic profiling test detected KRAS and TP53 mutations, leading to the final diagnosis of PDAC (fT3N1aM0, stage IIB). The patient received adjuvant S-1 chemotherapy and remained recurrence-free for 15 months post-surgery. This case highlights the diagnostic challenges of differentiating intraductal pancreatic tumors and demonstrates the utility of integrating genetic testing with conventional diagnostic modalities for an accurate diagnosis and appropriate treatment selection.

DOI： 10.1007/s12328-025-02098-y

Comparison of Midazolam and Diazepam for Sedation in Patients Undergoing Double-Balloon Endoscopic Retrograde Cholangiopancreatography: A Propensity Score-Matched Analysis. Reviewed International journal

Yuki Fujii, Kazuyuki Matsumoto, Akihiro Matsumi, Kazuya Miyamoto, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Toshiharu Mitsuhashi, Motoyuki Otsuka

Journal of clinical medicine 14 ( 7 ) 2025.3

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

Objective: The sedation method used in double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) varies across countries and between healthcare facilities. No previous studies have compared the effects of different benzodiazepines on sedation during endoscopic procedures. This study aimed to compare the effects of midazolam and diazepam sedation on DB-ERCP outcomes. Methods: This retrospective cohort study analyzed consecutive patients who underwent DB-ERCP between January 2017 and February 2024. A total of 203 patients who were sedated with diazepam (n = 94) or midazolam (n = 109) were analyzed. Propensity score matching was applied to adjust for baseline group differences. The primary outcome was the incidence of sedation-related adverse events (AEs). Secondary outcomes included inadequate sedation requiring additional sedatives and risk factors for sedation-related AEs. Results: Sedation-related AEs were more frequent with diazepam (28% [21/75]) than with midazolam (14% [11/75]; p = 0.046). Hypoxia occurred more frequently with diazepam (19% [14/75]) than with midazolam (5% [4/75]; p = 0.012). However, no significant differences were observed between the two groups for hypotension (p = 0.41) and bradycardia (p = 1.0). Poor sedation requiring other sedatives occurred significantly more often with diazepam (8% [6/75]) compared with midazolam sedation (0% [0/75], p = 0.012). Multivariate analysis identified diazepam sedation (odds ratio, 2.3; 95% confidence interval, 1.0-5.3; p = 0.048) as the sole risk factor for sedation-related AEs. Conclusions: Midazolam is safer and more effective than diazepam sedation in patients undergoing DB-ERCP.

DOI： 10.3390/jcm14072287

Clinical Significance of Lymphatic Involvement in Intramucosal (pT1a) Gastric Cancer Resected by Endoscopic Submucosal Dissection. Reviewed International journal

Katsunori Matsueda, Yoshiyasu Kono, Koji Miyahara, Masahiro Nakagawa, Hirokazu Mouri, Kazuhiro Matsueda, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Takehiro Tanaka, Motoyuki Otsuka

Journal of gastroenterology and hepatology 40 ( 3 ) 712 - 719 2025.3

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

BACKGROUND AND AIM: Lymphatic involvement is sometimes detected during routine examination of intramucosal (pT1a) gastric cancer resected endoscopically. However, its clinical significance and association with the risk of metastasis remain unknown. METHODS: This was a retrospective cohort study of 6797 consecutive patients with pT1a gastric cancers treated by endoscopic submucosal dissection (ESD) at three institutions in Japan from January 2005 to August 2023. Patients with 49 uncommon-type gastric cancer types were excluded. The risk of metastasis for pT1a cancers with lymphatic involvement was quantified by comparing lymph node metastasis and/or metastatic recurrence in patient groups who underwent additional surgery post-ESD or did not undergo surgery but were followed up for > 3 years. RESULTS: Among the 6748 pT1a cancers treated by ESD, 41 lesions (0.6%) had histologically confirmed lymphatic involvement. Among the 41 patients, 1 was excluded from the analysis of metastasis risk because the follow-up period after ESD without additional surgery was ≤ 3 years. Metastasis was identified in 1 of 40 patients analyzed (2.5%; 95% confidence interval [CI] 0.4%-12.9%), and was not detected in any of the 25 patients with pure differentiated-type lesions (0.0%; 95% CI 0.0%-13.7%). CONCLUSIONS: The low prevalence of metastasis after ESD for pT1a gastric cancer with lymphatic involvement, particularly in patients with pure differentiated-type lesions, suggests a low risk of metastatic recurrence.

DOI： 10.1111/jgh.16854

Cholecystectomy Is Linked to Worse Clinical Outcomes in Primary Sclerosing Cholangitis. Reviewed International journal

Nozomi Miyake, Kengo Yasugi, Akinobu Takaki, Kazuyuki Matsumoto, Motoyuki Otsuka

Cureus 17 ( 3 ) e80184 2025.3

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

Recent findings have suggested that gallbladder-derived retinoic acid signaling plays a crucial role in the regeneration of damaged intrahepatic biliary ducts. This retrospective cohort study analyzed the clinical records of 20 patients with primary sclerosing cholangitis (PSC) treated at our hospital between 2013 and 2024. We investigated the clinical implications of gallbladder removal in patients with PSC, a progressive cholangiopathy with limited therapeutic options. We retrospectively analyzed the data of patients with PSC and compared patients with and without prior cholecystectomy to assess the impact on disease progression using the Mayo risk score, Fibrosis-4 (FIB4) index, and other clinical parameters. Our findings indicated that cholecystectomy was associated with worse Mayo risk scores (p = 0.0004) and an elevated FIB4 index (p = 0.021), suggesting a potential link between gallbladder removal and accelerated disease progression. Furthermore, mortality and transplant-free survival analysis revealed significantly worse outcomes in the cholecystectomy group (odds ratio = 21.0, p = 0.032). However, given the retrospective nature and small sample size of this study, selection bias cannot be excluded, and further research is needed to confirm these findings. These findings support the hypothesis that gallbladder-derived factors, such as retinoic acid, may influence PSC progression and highlight the need for further research into therapeutic interventions targeting this pathway.

DOI： 10.7759/cureus.80184

The benefit of conversion therapy for patients with unresectable hepatocellular carcinoma receiving atezolizumab plus bevacizumab using newly established oncological resectability criteria in Japan. Reviewed International journal

Shigeo Shimose, Issei Saeki, Takanori Ito, Yasuto Takeuchi, Joji Tani, Tetsu Tomonari, Ryu Sasaki, Kyo Sasaki, Satoru Kakizaki, Takeshi Hatanaka, Hideki Iwamoto, Norikazu Tanabe, Takafumi Yamamoto, Atsushi Naganuma, Tomotake Shirono, Yuki Kanayama, Sohji Nishina, Tetsuji Takayama, Hideki Kobara, Motoyuki Otsuka, Hiroki Kawashima, Taro Takami, Takumi Kawaguchi

Hepatology international 19 ( 4 ) 846 - 855 2025.2

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

BACKGROUND: This study aimed to investigate the changes in oncological resection status in patients with unresectable hepatocellular carcinoma (u-HCC) receiving atezolizumab plus bevacizumab (Atez/Bev) and the impact of conversion therapy following Atez/Bev treatment. METHODS: This cohort included 631 patients with u-HCC treated with Atez/Bev. Tumors were assessed using oncological resectability criteria and categorized as borderline resectable 1 (BR1, n=166) or borderline resectable 2 (BR2, n=465). RESULTS: Overall, 129 (20.4%) patients were downstaged based on oncological resectability criteria. Among them, 28 (16.8%) patients were downstaged from BR1 to resectable (R), and 49 (10.5%) and 52 (11.1%) patients were downstaged from BR2 to R and from BR2 to BR1, respectively. The percentage of patients who underwent conversion therapy was 5.4%. For patients categorized as BR1 and BR2 before Atez/Bev treatment, the rates of conversion therapy were 8.4% (14/166) and 4.3% (20/465), respectively. Overall survival (OS) was significantly higher in the conversion therapy group than in the partial response group (not reached vs. 36.4 months, p=0.001), with no significant differences compared to the complete response group. The median recurrence-free survival was 15.7 months after conversion therapy. Although there were differences in patient background data at the time of conversion therapy, surgery had a significantly higher RFS than radiofrequency ablation (not reached vs. 10.0 months, p=0.008). CONCLUSIONS: When feasible, conversion therapy should be considered to improve the prognosis of u-HCC patients treated with Atez/Bev. Moreover, oncological resectability criteria may provide a useful tool for investigators regarding conversion therapy.

DOI： 10.1007/s12072-025-10781-y

Advanced prostate cancer diagnosed through colonoscopy. Reviewed International journal

Masaya Iwamuro, Takehiro Tanaka, Seiji Kawano, Nobumasa Ikeda, Motoyuki Otsuka

Gastrointestinal endoscopy 102 ( 2 ) 300 - 301 2025.2

Unraveling a Rare Case: Diarrhea, Alopecia, and Polyposis. Reviewed International journal

Hidetaka Mizushima, Hideaki Kinugasa, Motoyuki Otsuka

Gastroenterology 169 ( 2 ) 218 - 220 2025.2

Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis. Reviewed International journal

Yuki Aoyama, Sakiko Hiraoka, Eriko Yasutomi, Toshihiro Inokuchi, Takehiro Tanaka, Kensuke Takei, Shoko Igawa, Keiko Takeuchi, Masahiro Takahara, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Jun Kato, Hiroyuki Okada, Motoyuki Otsuka

Scientific reports 15 ( 1 ) 5248 - 5248 2025.2

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

Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level.

DOI： 10.1038/s41598-025-89615-8

Clinical Variables that Predict Liver-related Events in Steatotic Liver Disease Diagnosed by a Liver Biopsy. Reviewed

Shinnosuke Okubo, Akinobu Takaki, Ikumi Sato, Takuya Adachi, Yasuto Takeuchi, Masahiko Sue, Nozomi Miyake, Hideki Onishi, Satoshi Hirohata, Motoyuki Otsuka

Internal medicine (Tokyo, Japan) 2025.2

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

Objective Identifying patients at high risk of steatotic liver disease (SLD) is crucial. The liver fibrosis stage is the most reliable marker of liver-related mortality. However, noninvasive risk stratification methods remain controversial. Therefore, we analyzed the risk of liver-related events in patients who underwent a liver biopsy for metabolic dysfunction-associated steatotic liver disease (MASLD) or cryptogenic SLD at our hospital. Methods We retrospectively reviewed the clinical course of the patients to identify the occurrence of liver-related events. Patients This study included 146 patients diagnosed with SLD through a liver biopsy. Results Liver-related events occurred in 20 patients and were more frequent in those with advanced fibrosis than in those without advanced fibrosis. However, patients with advanced steatosis exhibit reduced disease progression. Patients with obesity and/or diabetes complications had a lower stage of fibrosis and better prognosis than the others. The non-invasive fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease (NAFLD) prognosis-related "NAFLD outcomes score (NOS)" effectively differentiated patients with disease progression. Standard laboratory data analyses revealed that high total bilirubin and low albumin levels were risk factors. A multivariate analysis with significant factors other than NOS score revealed that the absence of obesity and/or diabetes complications, a high FIB-4 index, and a high total bilirubin level were independent factors for liver-related events. Conclusion A high NOS score, absence of obesity and/or diabetes complications, a high FIB-4 index, and high total bilirubin levels are risk factors for disease progression. Patients with lean phenotypes or non-diabetic SLD should also be assessed using noninvasive markers to determine their risks and potential outcomes.

DOI： 10.2169/internalmedicine.4770-24

Natural Course and Long-Term Outcomes of Gastric Subepithelial Lesions: A Systematic Review. Reviewed International journal

Masaya Iwamuro, Hiroyuki Okada, Motoyuki Otsuka

Journal of clinical medicine 14 ( 4 ) 2025.2

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

Background/Objectives: Gastric subepithelial lesions (SELs) are often incidentally detected during endoscopic examinations, with most patients being asymptomatic and lesions measuring <20 mm. Despite their generally indolent nature, certain SELs, such as gastrointestinal stromal tumors, require resection. Current guidelines recommend periodic surveillance; however, the natural course and long-term outcomes of gastric SELs have not been sufficiently investigated. This systematic review aimed to synthesize evidence on the progression, growth rate, and risk factors associated with gastric SELs to inform clinical management strategies. Methods: A comprehensive search of PubMed was conducted for peer-reviewed studies published between January 2000 and November 2024. Eligible studies included original studies on the follow-up and progression of gastric SELs. Non-English articles, reviews, case reports, and unrelated topics were excluded. In total, 277 articles were screened, with 15 additional articles identified through manual screening. Ultimately, 41 articles were included in the analysis. The study protocol is registered in PROSPERO (CRD42024614865). Results: Large-scale studies reported low growth rates of 2.0-8.5% over 2.0-5.0 years, while smaller studies reported a broader range of growth rates of 5.4-28.4%. The factors contributing to these discrepancies include patient selection, follow-up duration, and growth criteria. Risk factors for lesion size increase include larger initial lesion size, irregular margins, heterogeneous echo patterns, and certain tumor locations. Conclusions: These findings underscore the need for individualized management strategies based on lesion size, imaging characteristics, and risk factors. The close monitoring of high-risk lesions is crucial for timely intervention. Standardized growth criteria and optimized follow-up protocols are essential for improving clinical decision making and patient outcomes.

DOI： 10.3390/jcm14041055

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

Gastric Metastasis of Renal Cell Carcinoma Initially Diagnosed by Esophagogastroduodenoscopy. Reviewed International journal

Masaya Iwamuro, Tomohiro Kamio, Shoichiro Hirata, Takehiro Tanaka, Motoyuki Otsuka

Cureus 17 ( 2 ) e79651 2025.2

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

Here, we report a rare case of renal cell carcinoma (RCC) initially detected as a gastric metastasis. A 58-year-old man with epigastric discomfort underwent esophagogastroduodenoscopy, which revealed a reddish semi-pedunculated lesion with a whitish coating. Biopsy and imaging confirmed clear cell RCC metastasis. Contrast-enhanced computed tomography (CT) revealed a primary renal tumor with pancreatic and lymph node metastases. Despite chemotherapy treatment, the patient died after 10 months. Gastric metastases from RCC, although rare, should be considered in highly vascular gastric lesions with white coatings. Clinicians must be vigilant for metastatic diseases with atypical gastric findings.

DOI： 10.7759/cureus.79651

Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0. Reviewed International journal

Di Wu, Jia-Horng Kao, Teerha Piratvisuth, Xiaojing Wang, Patrick T F Kennedy, Motoyuki Otsuka, Sang Hoon Ahn, Yasuhito Tanaka, Guiqiang Wang, Zhenghong Yuan, Wenhui Li, Young-Suk Lim, Junqi Niu, Fengmin Lu, Wenhong Zhang, Zhiliang Gao, Apichat Kaewdech, Meifang Han, Weiming Yan, Hong Ren, Peng Hu, Sainan Shu, Paul Yien Kwo, Fu-Sheng Wang, Man-Fung Yuen, Qin Ning

Clinical and molecular hepatology 31 ( Suppl ) S134-S164 2025.2

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

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

DOI： 10.3350/cmh.2024.0780

Bleeding Risk During Colorectal Endoscopic Mucosal Resection With Continued Anticoagulant Therapy: A Multicenter Study. Reviewed International journal

Sayo Kobayashi, Keita Harada, Toru Nawa, Tomoo Fujisawa, Toru Ueki, Junichiro Nasu, Yuki Morito, Tatsuya Toyokawa, Tomoki Inaba, Masahide Kita, Ryuta Takenaka, Masafumi Inoue, Reiji Higashi, Takao Tsuduki, Minoru Matsubara, Yasushi Yamasaki, Hiroyuki Okada, Motoyuki Otsuka

Cureus 17 ( 1 ) e76753 2025.1

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

Background and aims Endoscopic mucosal resection (EMR) is a standard preventive method for colorectal cancer. Managing patients on anticoagulants during EMR is challenging because of balancing bleeding and thrombotic risks. Updated guidelines recommend continuing anticoagulants over heparin bridging; however, data on bleeding risks with continuing anticoagulants remain limited. This multicenter prospective study evaluated bleeding rates in patients who continued oral anticoagulants during EMR. Methods Patients on warfarin or direct oral anticoagulants (DOACs) undergoing EMR were enrolled from 12 tertiary hospitals. Warfarin was maintained on the day of EMR, while DOACs were paused on the day of EMR and resumed afterward. Post-EMR mucosal defects were closed with clips per protocol. Adverse events were monitored for 30 days. The primary endpoint was the major bleeding rate, defined as immediate bleeding requiring difficult hemostasis or delayed bleeding necessitating endoscopic intervention. The secondary endpoints were minor bleeding, other adverse events, and differences in bleeding rates between warfarin and DOACs. Results Among 107 patients (341 polyps; mean size = 6.7 mm), major bleeding occurred in five (4.7%) patients (95% confidence interval: 2.0%-10.5%), and all cases were managed endoscopically. Minor bleeding and thromboembolism events occurred in eight (7.5%) patients and one (0.9%) patient, respectively. No significant differences in bleeding rates were observed between warfarin and DOACs. Major bleeding rates were lower than those reported for heparin bridging. Conclusions Continuing anticoagulant therapy during EMR was associated with a low major bleeding rate (4.7%) and minimal thrombotic events, supporting its safety as an alternative to heparin bridging.

DOI： 10.7759/cureus.76753

Clipping closure length is a crucial factor for delayed bleeding after endoscopic papillectomy: a retrospective multicenter cohort study. Reviewed International journal

Yuki Fujii, Kazuyuki Matsumoto, Kiyoaki Ochi, Hitomi Himei, Ichiro Sakakihara, Eijiro Ueta, Tatsuya Toyokawa, Ryo Harada, Taiji Ogawa, Takeshi Tomoda, Hironari Kato, Ryosuke Sato, Taisuke Obata, Akihiro Matsumi, Kazuya Miyamoto, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Motoyuki Otsuka

Therapeutic advances in gastroenterology 18 17562848251326450 - 17562848251326450 2025

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

BACKGROUND: Bleeding is a serious and frequent adverse event that occurs during and after endoscopic papillectomy (EP). Previous studies have highlighted the effectiveness of preventive clipping closure of the resection site in preventing post-EP bleeding. However, the optimal length of closure remained unclear. OBJECTIVES: We aimed to clarify the optimal clipping length at the post-EP resection site to prevent delayed bleeding. DESIGN: This study was a multicenter retrospective cohort study. METHODS: We retrospectively analyzed patients who were consecutively admitted to nine high-volume centers for EP between November 2003 and October 2023. The primary outcome was the frequency of delayed bleeding based on the closure length. The optimal closure length rate of the resected site to prevent delayed bleeding was determined using a receiver operating characteristic curve. Secondary outcomes were the incidence, treatment outcomes, and risk factors for post-EP delayed bleeding. RESULTS: A total of 130 patients who underwent EP were analyzed. Delayed bleeding was observed in 22 (17%) patients, occurring more frequently in cases without clipping closure than in those with clipping closure (28% (13/47) vs 11% (9/83); p = 0.014). Among 83 patients who underwent clipping closure, delayed bleeding occurred more frequently with a closure length rate <65% than in those with a closure rate ⩾65% (25% (5/20) vs 6% (4/63); p = 0.019). Multivariate analysis showed that a closure rate <65% was the risk factor for delayed bleeding (odds ratio, 6.3; 95% confidence interval, 1.2-33; p = 0.030) in cases with clipping. CONCLUSION: Clipping closure was effective in preventing delayed bleeding, and closure length rate ⩾65% of the resected site significantly reduced post-EP delayed bleeding.

DOI： 10.1177/17562848251326450

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