研究者詳細 - 大塚　基之

論文 - 大塚　基之

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Underwater endoscopic papillectomy of a duodenal adenoma extending to the papilla using a forward-viewing endoscope. 国際誌

Takashi Yamamoto, Yasushi Yamasaki, Yuki Fujii, Kazuyuki Matsumoto, Motoyuki Otsuka

Endoscopy 57 ( S 01 ) E667-E668 2025年12月

Temporal changes in computed tomography findings of a persimmon bezoar: A case report. 国際誌

Masaya Iwamuro, Tomoki Yoshikawa, Tomohiro Kamio, Shoichiro Hirata, Katsunori Matsueda, Daisuke Kametaka, Motoyuki Otsuka

World journal of clinical cases 13 ( 18 ) 103426 - 103426 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Gastric bezoars are masses of indigestible material that accumulate in the stomach, causing nausea, abdominal pain, and vomiting. Persimmon bezoars (diospyrobezoars), which comprise tannins and fibers from persimmons, are relatively rare but may cause significant gastric complications, including gastric outlet obstruction or ileus. Although computed tomography (CT) is a useful imaging tool, diagnosing bezoars can be challenging because their density is similar to that of food debris and gastric content. CASE SUMMARY: Here, we report the case of a 72-year-old woman with a persimmon bezoar that was diagnosed using serial CT imaging and confirmed by endoscopy. CT performed over several months revealed changes in the internal structure and density of the bezoar, suggesting progressive hardening. The patient had a history of a partial gastrectomy and excessive persimmon consumption, both of which are risk factors for bezoar formation. Endoscopic fragmentation of the bezoar successfully resolved symptoms. CONCLUSION: Gastric bezoars, particularly persimmon bezoars, present diagnostic challenges because of their variable imaging characteristics. Serial CT can document temporal changes in bezoar density, potentially reflecting changes in hardness. Early diagnosis and endoscopic treatment are essential for effective management, particularly in patients with predisposing factors. This case underscores the importance of considering bezoars in the differential diagnosis of gastric masses, and highlights the value of CT for monitoring changes in bezoar characteristics over time.

DOI： 10.12998/wjcc.v13.i18.103426

Distinct age-related effects of homologous recombination deficiency on genomic profiling and treatment efficacy in gastric cancer.

Yoshie Maki, Yoshiyasu Kono, Toshiki Ozato, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Kenta Hamada, Masaya Iwamuro, Seiji Kawano, Motoyuki Otsuka

Journal of gastroenterology 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The incidence of gastric cancer among younger patients is increasing globally, with growing attention being paid to the role of homologous recombination deficiency (HRD). However, the effect of HRD on treatment outcomes and prognosis in this population remains unclear. METHODS: We analyzed clinical and genomic data from the Center for Cancer Genomics and Advanced Therapeutics database. Younger patients (≤ 39 years, n = 140) were compared with older patients (≥ 65 years, n = 1118) diagnosed with gastric cancer. This study focused on mutations in homologous recombination repair (HRR) genes and their association with tumor mutation burden (TMB), microsatellite instability (MSI), and treatment outcomes. RESULTS: In older patients, HRD was associated with higher TMB and microsatellite instability-high (MSI-H) status, whereas no such correlations were observed in younger patients. Notably, MSI-H status was not observed in the younger group. Younger patients with HRD had a significantly shorter time to treatment failure (TTF) and overall survival (OS) than those without HRD. Conversely, in older patients, there was no significant difference in TTF or OS based on HRD status. CONCLUSION: HRR gene mutations influence genomic profiling, TMB, and MSI differently depending on the age of gastric cancer onset, suggesting potential effects on treatment efficacy and prognosis.

DOI： 10.1007/s00535-025-02267-3

The new assay type IV collagen 7S (CLEIA) is a useful test to identify progressive fibrosis in chronic liver disease: A study based on magnetic resonance elastography. 国際誌

Miwa Kawanaka, Takashi Fushimi, Tomohiro Tanikawa, Noriiyo Urata, Ken Haruma, Hirofumi Kawamoto, Motoyuki Otsuka

Hepatology research : the official journal of the Japan Society of Hepatology 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Liver fibrosis is a critical prognostic factor for chronic liver disease that influences morbidity and mortality. Type IV collagen 7S, measured using a chemiluminescent enzyme immunoassay, was evaluated as a novel noninvasive biomarker with its cutoff value determined via magnetic resonance elastography (MRE) to eliminate sampling bias. A two-step approach combining the fibrosis-4 (FIB-4) index and type IV collagen 7S demonstrated potential in enhancing risk stratification and clinical utility. METHODS: This study included 307 patients with chronic liver disease and 235 with metabolic dysfunction-associated steatotic liver disease. Type IV collagen 7S was compared with biomarkers such as FIB-4 index, M2BPGi, and hyaluronic acid. Diagnostic accuracy was assessed using AUROC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value, with cutoffs determined via the Youden Index. Subgroup analyses evaluated performance based on ALT levels (≤30 and >30 U/L) and age (≤60 and >60 years). A two-step risk stratification model incorporating type IV collagen 7S was developed for intermediate FIB-4 index groups (1.3-2.66) to assess its utility. RESULTS: For liver stiffness assessed using MRE, type IV collagen 7S showed the highest correlation (ρ = 0.591, p < 0.001) and outperformed other biomarkers, particularly for F ≥ 2. Its performance was notable in patients with low ALT levels (≤30 U/L) and in elderly patients (>60 years). In the intermediate FIB-4 index group, the two-stage model reduced over triage by 20%, increased specificity from 55% to 78% and enhanced PPV by 13%. CONCLUSIONS: The novel assay, type IV collagen 7S, is a highly effective and noninvasive biomarker for liver fibrosis. The performance of type IV collagen 7S tends to have robustness under the difference of ALT. Its combination with the FIB-4 index enhances diagnostic precision, particularly in intermediate-risk patients, reinforcing its role in refining fibrosis staging and optimizing patient management.

DOI： 10.1111/hepr.14202

A study on the timing of small-bowel capsule endoscopy and its impact on the detection rate of bleeding sources. 国際誌

Daisuke Kametaka, Masaya Iwamuro, Toshihiro Inokuchi, Seiji Kawano, Sakiko Hiraoka, Motoyuki Otsuka

BMC gastroenterology 25 ( 1 ) 434 - 434 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Small-bowel capsule endoscopy (SBCE) is an essential diagnostic tool for obscure gastrointestinal bleeding, particularly for identifying bleeding sources in the small intestine. The timing of SBCE is thought to affect its diagnostic yield; however, the optimal timing remains unknown. METHODS: This retrospective study analyzed 131 patients with overt gastrointestinal bleeding managed with SBCE at our institution between May 2015 and December 2022. Patients were categorized into four groups based on the interval between their last bleeding episode and SBCE: 1–7, 8–14, 15–28, and ≥ 29 days. RESULTS: Positive findings were observed in approximately 50% of the cases across all intervals, with no statistically significant differences in the detection rates. Vascular lesions were detected primarily within 1–14 days, whereas inflammatory lesions, tumors, and diverticula were identified across all intervals. Notably, 25% of the patients with negative SBCE findings were later diagnosed with sources of non-small bowel bleeding, highlighting the value of follow-up endoscopic evaluations. CONCLUSIONS: Our findings suggest that SBCE can be effective regardless of the time after a bleeding event, contrary to previous recommendations emphasizing its early use. Clinicians should consider performing SBCE whenever feasible to improve the diagnostic outcomes for gastrointestinal bleeding, irrespective of the elapsed time since the last episode.

DOI： 10.1186/s12876-025-04044-1

Corrigendum to Risk factors and treatment strategies for cholecystitis after metallic stent placement for malignant biliary obstruction: a multicenter retrospective study. Gastrointestinal Endoscopy. Volume 100, Issue 1, July 2024, Pages 76-84. 国際誌

Akihiro Matsumi, Hironari Kato, Taiji Ogawa, Toru Ueki, Masaki Wato, Masakuni Fujii, Tatsuya Toyokawa, Ryo Harada, Yuki Ishihara, Masahiro Takatani, Hirofumi Tsugeno, Naoko Yunoki, Takeshi Tomoda, Toshiharu Mitsuhashi, Motoyuki Otsuka

Gastrointestinal endoscopy 2025年6月

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

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 12 ( 2 ) 335 - 336 2025年6月

A novel approach to evaluate the therapeutic efficacy of durvalumab and tremelimumab combination therapy in hepatocellular carcinoma. 国際誌

Tetsu Tomonari, Shigeo Shimose, Issei Saeki, Joji Tani, Yuichi Honma, Takanori Ito, Mamiko Takeuchi, Takehito Naito, Yasuto Takeuchi, Ryu Sasaki, Kyo Sasaki, Takeshi Hatanaka, Satoru Kakizaki, Yuki Kanayama, Atsushi Naganuma, Norikazu Tanabe, Hironori Tanaka, Yutaka Kawano, Yasushi Sato, Sohji Nishina, Hisamitsu Miyaaki, Motoyuki Otsuka, Hiroki Kawashima, Masaru Harada, Hideki Kobara, Taro Takami, Takumi Kawaguchi, Tetsuji Takayama

Hepatology research : the official journal of the Japan Society of Hepatology 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize "stable disease (SD)," and identify SD responders (SD-R) who benefit from Dur + Tre treatment. METHODS: This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders. RESULTS: Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11). CONCLUSIONS: In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.

DOI： 10.1111/hepr.14212

Endoscopic Bridging Stent Placement Improves Bile Leaks After Hepatic Surgery. 国際誌

Taisuke Obata, Kazuyuki Matsumoto, Kei Harada, Nao Hattori, Ryosuke Sato, Akihiro Matsumi, Kazuya Miyamoto, Hiroyuki Terasawa, Yuki Fujii, Daisuke Uchida, Shigeru Horiguchi, Koichiro Tsutsumi, Motoyuki Otsuka

Journal of clinical medicine 14 ( 10 ) 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Endoscopic treatment is one of the first-line treatments for bile leaks after hepatic surgery. However, detailed reports of endoscopic treatment for bile leaks after hepatic resection (HR) or liver transplantation (LT) are scarce. The outcomes of endoscopic treatment for bile leaks after hepatic surgery were examined, and factors related to successful treatment were identified. Methods: A total of 122 patients underwent endoscopic treatment for bile leaks after hepatic surgery. The diagnosis of a bile leak is based on the ISGLS criteria. The decision to perform endoscopic retrograde cholangiography (ERC) is made based on the amount of drainage output, laboratory data, clinical symptoms, and CT scan findings. In our study, the site of the bile leak was assessed using ERC. Endoscopic stents were placed to bridge across the bile leak site as much as possible. Otherwise, stents were placed near the leak site. Endoscopic stents were replaced every 2-3 months until an improvement in the bile leak was observed with or without biliary strictures. The outcomes of endoscopic treatment and the factors related to clinical success were evaluated. Results: Seventy-four patients with HR and forty-eight patients with LT were treated endoscopically. Technical and clinical success was achieved in 89% (109/122) and 82% (100/122) of patients, respectively. Three (2%) patients died from uncontrollable bile leaks. Bridging stent placement (p < 0.001), coexistent percutaneous drainage (p = 0.0025), and leak severity (p = 0.015) were identified as independent factors related to the clinical success of endoscopic treatment. During a median observation period of 1162 days after the achievement of clinical success, bile leak recurrence was observed in only three cases (3%). Conclusions: Endoscopic treatment is safe and effective for bile leaks after hepatic surgery. Bridging stent placement across the leak site is the most crucial factor for clinical success.

DOI： 10.3390/jcm14103381

Efficient diagnosis for endoscopic remission in Crohn's diseases by the combination of three non-invasive markers. 国際誌

Kensuke Takei, Toshihiro Inokuchi, Sakiko Hiraoka, Mikako Ishiguro, Junki Toyosawa, Yuki Aoyama, Shoko Igawa, Keiko Takeuchi, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Seiji Kawano, Toshiharu Mitsuhashi, Motoyuki Otsuka

BMC gastroenterology 25 ( 1 ) 364 - 364 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Serum C-reactive protein (CRP), leucine-rich alpha-2 glycoprotein (LRG), and fecal calprotectin (Fcal) are non-invasive markers used to assess Crohn's disease (CD) severity. However, the accuracy of these markers alone is often limited, and most previous reports have evaluated the efficacy of each marker individually. We aimed to improve the diagnostic performance of endoscopic remission (ER) of CD by combining these 3 markers. METHODS: We tested the diagnostic ability of various combinations of these 3 markers for endoscopic severity in 230 consecutive patients with CD from September 2014 to July 2023. The modified Simple Endoscopic Score for Crohn's disease (mSES-CD) was used to determine endoscopic severity. RESULTS: Each of the 3 markers was correlated with mSED-CD (LRG: r = 0.69, CRP: r = 0.60, and Fcal: r = 0.67). A combination of 2 of the 3 markers did not increase the diagnostic accuracy of ER. However, by combining all 3 markers, the diagnostic ability for ER was improved in comparison to the diagnostic ability of the 3 individual markers, assuming that ER was obtained if 2 or 3 markers were negative. The sensitivity, specificity, and accuracy were 89%, 83%, and 86%, respectively. Additionally, we established a 2-step method using Fcal values after evaluating the 2 serum markers. This method was most useful for reducing both the patient burden and costs. CONCLUSIONS: The newly established 2-step method allowed for a higher accuracy in the non-invasive diagnosis of ER when the 3 markers were combined.

DOI： 10.1186/s12876-025-03880-5

Genomic landscape and clinical impact of homologous recombination repair gene mutation in small bowel adenocarcinoma. 国際誌

Toshiki Ozato, Yoshiyasu Kono, Shigeru Horiguchi, Koichiro Tsutsumi, Hideki Yamamoto, Akira Hirasawa, Daisuke Ennishi, Shuta Tomida, Shinichi Toyooka, Motoyuki Otsuka

European journal of cancer (Oxford, England : 1990) 220 115401 - 115401 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Although homologous recombination deficiency has been studied as a biomarker for other cancer types, the clinical and genomic implications of homologous recombination repair (HRR) gene mutations in SBA remain unclear. METHODS: We retrospectively analyzed the data of 628 patients with advanced or recurrent SBA from a nationwide genomic database. Patients were categorized into HRR mutation and non-HRR mutation groups and compared for their clinical and genomic characteristics including tumor mutational burden (TMB) and microsatellite instability-high (MSI-H) were compared. Treatment efficacy and overall survival (OS) were assessed based on HRR gene mutation status and primary tumor site (duodenal adenocarcinoma [DA] vs. small intestinal carcinoma [SIC]). RESULTS: Patients with the HRR mutations had higher frequencies of TMB and MSI-H than those without the mutation (P < 0.0001). In DA, HRR gene mutation positivity was associated with improved OS and higher overall response rates (ORR) to platinum-based chemotherapy (OS: not reached vs. 23.5 months, P = 0.040; ORR: 33 % vs. 19 %, P = 0.046), whereas no significant associations were observed with SIC. CONCLUSION: HRR gene mutation may be a potential biomarker for platinum-based chemotherapy efficacy in SBA, especially in DA, highlighting the need for site-specific therapies.

DOI： 10.1016/j.ejca.2025.115401

Successful removal of a buried lumen-apposing metal stent without complications using pancreatic drainage and a hemostatic agent. 国際誌

Yuki Fujii, Kazuyuki Matsumoto, Motoyuki Otsuka

Clinical endoscopy 58 ( 3 ) 476 - 477 2025年5月

Pseudoachalasia Due to Malignant Pleural Mesothelioma Involving the Esophagus. 国際誌

Manami Honda, Masaya Iwamuro, Kazuya Miyamoto, Takehiro Tanaka, Motoyuki Otsuka

Cureus 17 ( 5 ) e84161 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

We report a rare case of pseudoachalasia secondary to malignant pleural mesothelioma involving the esophagus. A 66-year-old man presented with progressive dysphagia, weight loss, and postprandial hiccups. Endoscopic examination showed esophageal dilation with luminal narrowing at the esophagogastric junction, but no mucosal abnormalities. Computed tomography revealed an irregular-shaped mass extending from the peri-esophagogastric junction to the retroperitoneum, accompanied by pleural effusion, right-sided hydronephrosis, and multiple hepatic lesions. Endoscopic ultrasound-guided fine-needle aspiration from the mass lesion through the esophageal lumen revealed epithelioid malignant mesothelioma. This case highlights the importance of considering malignant mesothelioma in the differential diagnosis of pseudoachalasia, particularly when imaging reveals extrinsic esophageal compression without mucosal lesions.

DOI： 10.7759/cureus.84161

High complete resection rates of underwater endoscopic mucosal resection for intermediate-sized sessile serrated lesions. 国際誌

Junki Toyosawa, Masayasu Ohmori, Yasushi Yamasaki, Yuki Aoyama, Shoko Igawa, Keiko Takeuchi, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Takehiro Tanaka, Motoyuki Otsuka

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Sessile serrated lesions (SSLs) pose a risk of carcinoma, necessitating endoscopic resection. Conventional endoscopic mucosal resection (EMR) often fails to achieve complete resection for intermediate-sized SSLs. Although underwater EMR (UEMR) is being increasingly used for colon polyps, its efficacy for SSLs remains unclear. This study evaluated the complete resection rate of UEMR for intermediate-sized SSLs. METHODS: This prospective, single-arm, observational study was conducted at two institutions. Patients with endoscopically diagnosed intermediate-sized SSLs (10-20 mm) were enrolled. UEMR was performed, and specimens were histologically assessed. Post-UEMR lesions were closely examined, and biopsies were taken to check for residuals. Follow-up colonoscopy was performed 1 year later to evaluate recurrence. The primary end-point was the complete resection rate, defined as no residual in biopsy specimens. The secondary end-points were the rates of R0 resection, en bloc resection, recurrence, adverse events, and factors regarding procedural difficulty. RESULTS: In total, 103 patients with 133 lesions were consecutively identified. Twenty-seven cases with 30 lesions were excluded by criteria; 103 endoscopically diagnosed SSLs were enrolled. The median postresection lesion size was 12 mm (range 8-23). The R0 and en bloc resection rates were 61% and 91%, respectively. The overall complete resection rate was 97% (95% confidence interval 91.8-99.0%). Follow-up colonoscopy in 87 lesions showed no recurrence. Only one patient (1%) experienced delayed bleeding. Snaring difficulty was significantly associated with piecemeal resection. CONCLUSION: The complete resection rate of UEMR for intermediate-sized SSLs was acceptable. UEMR may become a standard treatment for intermediate-sized SSLs.

DOI： 10.1111/den.15035

Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders.

Shoichiro Hirata, Tomohiro Kamio, Takuya Satomi, Kenta Hamada, Hiroyuki Sakae, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Noriaki Manabe, Motoyuki Otsuka

Internal medicine (Tokyo, Japan) 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

This report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits.

DOI： 10.2169/internalmedicine.4943-24

Gastrointestinal Stromal Tumors in the Stomach With Tumor Growth and Hemorrhage During Conservative Management: A Report of Two Cases. 国際誌

Masaya Iwamuro, Satoru Kikuchi, Shinji Kuroda, Takehiro Tanaka, Motoyuki Otsuka

Cureus 17 ( 4 ) e82046 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Gastrointestinal stromal tumors (GISTs) are often detected incidentally during esophagogastroduodenoscopy. Although surgical resection is the standard treatment for GISTs, patients with significant comorbidities may not be eligible for surgery and are managed conservatively. Herein, we report two cases of gastric GISTs that were initially observed during the management of other comorbidities but subsequently became enlarged, resulting in gastrointestinal bleeding. These cases highlight the potential risks of tumor progression and bleeding in patients undergoing conservative management.

DOI： 10.7759/cureus.82046

Antitumor effects and immune-mediated adverse events of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma. 国際誌

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

Hepatology research : the official journal of the Japan Society of Hepatology 55 ( 4 ) 577 - 587 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre. METHODS: We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment. RESULTS: Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (n = 10), liver injury (n = 9), interstitial lung disease (n = 5), rashes (n = 4), cytokine-release syndrome/fever (n = 2), pancreatitis (n = 2), and others (n = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (p = 0.026), the frequency of severe imAEs was not significantly different (p = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively). CONCLUSIONS: Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.

DOI： 10.1111/hepr.14151

Frequency and Characteristics of Gastrointestinal Diseases in Patients With Neurofibromatosis. 国際誌

Manami Honda, Masaya Iwamuro, Takehiro Tanaka, Yasushi Yamasaki, Seiji Kawano, Sakiko Hiraoka, Yoshiro Kawahara, Motoyuki Otsuka

JGH open : an open access journal of gastroenterology and hepatology 9 ( 4 ) e70151 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Patients with neurofibromatosis (NF) frequently experience gastrointestinal symptoms, but the specific characteristics of these lesions are not well understood. METHODS: To investigate the prevalence and nature of gastrointestinal diseases in this population, we analyzed the gastrointestinal lesions identified through endoscopic examinations in patients with NF. RESULTS: We included 225 patients with NF type 1 (NF1) and 15 with NF type 2 (NF2). None of the NF2 patients underwent endoscopy. Among the NF1 patients, 27 received endoscopies, and 13 (59%) had gastrointestinal lesions. These 13 patients were predominantly male (10 males and three females), with a median age of 53 years (range: 19-76 years). The identified lesions included colorectal polyps (n = 6), gastrointestinal stromal tumors ([GIST], n = 4), subepithelial lesions (n = 3), gastric fundic gland polyps (n = 3), diffuse intestinal ganglioneuromatosis (n = 2), esophageal polyps (n = 2), a Schwann cell hamartoma (n = 1), esophageal cancer (n = 1), and a gastric hyperplastic polyp (n = 1). All GISTs and one case of diffuse intestinal ganglioneuromatosis were surgically resected. Interestingly, six out of 13 patients were asymptomatic. Additionally, all patients who required surgery were 40 years of age or older. CONCLUSIONS: These findings suggest that routine endoscopic examinations, along with imaging techniques like computed tomography and magnetic resonance imaging, could be beneficial for the early detection of gastrointestinal lesions in NF1 patients aged 40 and above.

DOI： 10.1002/jgh3.70151

Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer. 国際誌

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

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年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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