慶應義塾大学医学部 病理学教室 組織病理学分野

@article{Miyazawa2026,

title = {Primary leiomyosarcoma of the portal vein: A progressively enhancing fusiform mass without biliary dilatation as a rare differential for hilar tumors},

author = {Azumi Miyazawa and Junya Tsuzaki and Ryo Ogawa and Masashi Tamura and Nana Osaki and Keiichi Miyashita and Yuta Abe and Yutaka Nakano and Kensuke Hara and Hidenori Ojima and Shigeo Okuda and Shigeki Sekine and Yuko Kitagawa and Masahiro Jinzaki},

doi = {10.1016/j.radcr.2026.03.028},

issn = {1930-0433},

year  = {2026},

date = {2026-07-00},

journal = {Radiology Case Reports},

volume = {21},

number = {7},

pages = {2715--2721},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41850249,

title = {Early-Onset Digestive System Cancers: Risk Factors and Clinicopathological and Molecular Features Across Organ Sites},

author = {Nobuhiro Nakazawa and Satoko Ugai and Atsushi Kondo and Kosuke Matsuda and Shu Kato and Genki Usui and Shiori Tanaka and Hwa-Young Lee and Xinyuan Zhang and Hideo Miyagawa and Mai Chan Lau and Hiroshi Saeki and Yukihide Kanemitsu and Andrew T Chan and Shuji Ogino and Minkyo Song and Juha P Väyrynen and Tomotaka Ugai},

doi = {10.1111/cas.70363},

issn = {1349-7006},

year  = {2026},

date = {2026-05-01},

urldate = {2026-05-01},

journal = {Cancer Sci},

volume = {117},

number = {5},

pages = {1223--1234},

abstract = {The incidence of early-onset cancers, commonly defined as cancers diagnosed before age 50 years, has been increasing globally over recent decades. In particular, the incidence of several early-onset digestive system cancers, including cancers of the esophagus, stomach, colorectum, liver, extrahepatic bile duct, gallbladder, and pancreas, has been reported to be increasing in multiple regions. To elucidate carcinogenic mechanisms and develop effective prevention, earlier detection, and treatment strategies, further evidence is needed on risk factors and clinical, pathological, and molecular characteristics. In this review, we summarize the current evidence on these characteristics, highlight shared and distinct features across organ sites, and discuss research opportunities to address the rising burden of early-onset digestive system cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41593272,

title = {Background Liver Fibrosis as a Microenvironmental Risk Factor for Intrahepatic Recurrence in Colorectal Liver Metastases},

author = {Satoru Morita and Koji Okabayashi and Yutaka Endo and Yutaka Kurebayashi and Yohei Masugi and Tokiya Abe and Yasushi Hasegawa and Yuta Abe and Minoru Kitago and Ryo Seishima and Kohei Shigeta and Yuko Kitagawa},

doi = {10.1245/s10434-025-19017-7},

issn = {1534-4681},

year  = {2026},

date = {2026-05-01},

journal = {Ann Surg Oncol},

volume = {33},

number = {5},

pages = {3899--3909},

abstract = {BACKGROUND: Colorectal cancer liver metastases (CRLMs) are a frequent pattern of recurrence, yet the prognostic impact of background liver fibrosis remains unclear. This study aimed to quantitatively assess hepatic fibrosis histologically and determine its association with intrahepatic recurrence after resection.nnMETHODS: Patients who underwent hepatic resection for CRLM between 1999 and 2022 were retrospectively included in this study. Background liver fibrosis was evaluated histologically and quantified via whole-slide imaging. Fibrosis was analyzed as a continuous variable using Cox proportional hazards modeling. Additionally, patients were stratified into two groups (fibrosis vs non-fibrosis) using a cutoff determined by receive operating characteristic (ROC) analysis.nnRESULTS: Among 102 patients, 24 (23.5%) were classified into the fibrosis group. Intrahepatic recurrence after hepatic surgery occurred for 36.3% of all the patients, with a significantly higher rate in the fibrosis group than in the non-fibrosis group (58.3% vs 29.5%; p = 0.019), whereas no significant differences were observed in extrahepatic recurrence between the groups (41.7% vs 43.6%; p = 1.0). In the multivariable analysis, fibrotic area percentage was independently associated with intrahepatic recurrence (hazard ratio, 1.45; 95% confidence interval, 1.06-1.98; p = 0.02), demonstrating a linear relationship between fibrosis extent and recurrence risk.nnCONCLUSION: Histopathologically quantified background liver fibrosis is an independent risk factor for intrahepatic recurrence after CRLM resection. These findings underscore the potential role of the liver microenvironment in tumor recurrence and support further studies exploring hepatic fibrosis as a biomarker for postoperative risk stratification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41647691,

title = {Conversion Surgery after Chemotherapy in a Stage IV  V600E-Mutated Laterally Spreading Tumor With Neuroendocrine Component},

author = {Reona Kawamura and Naoya Toyoshima and Masau Sekiguchi and Hiroyuki Takamaru and Masayoshi Yamada and Nozomu Kobayashi and Hidekazu Hirano and Yasuyuki Takamizawa and Taiki Hashimoto and Yutaka Saito},

doi = {10.1002/deo2.70283},

issn = {2692-4609},

year  = {2026},

date = {2026-04-01},

journal = {DEN Open},

volume = {6},

number = {1},

pages = {e70283},

abstract = {We report a rare case of a  V600E-mutated laterally spreading tumor, granular type (LST-G), with a neuroendocrine carcinoma (NEC) component in a patient with stage IV colorectal cancer. The patient presented with multiple lymph nodes and liver metastases. Following systemic chemotherapy, significant regression of both the primary lesion and metastases was achieved, enabling successful conversion surgery. Postoperative pathological analysis post-surgery revealed only well-differentiated tubular adenocarcinoma, with complete disappearance of the NEC component. Molecular testing confirmed the persistence of the  V600E mutation. The patient remains recurrence-free two years after surgery. This case highlights the potential for conversion surgery in stage IV -mutated colorectal cancer with NEC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41975025,

title = {Morphological characteristics of the renal lesion in TAFRO syndrome and POEMS syndrome: a retrospective and multicenter study},

author = {Naoko Masuzawa and Yuko Ono and Hiroko Kakita and Wako Yumura and Akinori Hashiguchi and },

doi = {10.1007/s10157-026-02864-3},

issn = {1437-7799},

year  = {2026},

date = {2026-04-01},

journal = {Clin Exp Nephrol},

abstract = {BACKGROUND: TAFRO syndrome (TAFRO) and POEMS syndrome (POEMS) are rare systemic inflammatory diseases with significant clinical, histological, and immunological overlaps with idiopathic multicentric Castleman disease (iMCD). While a high incidence of renal symptoms is observed in TAFRO and POEMS, the specific histopathological differences in their renal manifestations are not fully understood.nnMETHODS: This retrospective, multicenter study was conducted by the Japanese Renal Pathology Society (JRPS). Eighteen patients with TAFRO (n = 7), POEMS (n = 6), and iMCD (n = 5) were registered by members of the JRPS, and their clinicopathological findings were analyzed. Morphological examinations were performed using light, fluorescence, and electron microscopy. Immunohistochemical studies and semi-quantitative scoring systems have been used for detailed assessment of glomerular lesions.nnRESULTS: Clinical data indicated that the time from disease onset to biopsy was significantly shorter in TAFRO patients than POEMS patients. Although immunosuppressive therapy induced improvement in all TAFRO patients, some POEMS patients exhibited a poor renal prognosis. Glomerular endothelial injury was observed in both the TAFRO and POEMS; however, the characteristics differed: the former displayed endotheliosis, whereas the latter exhibited membranoproliferative glomerulonephritis (MPGN)-pattern injury. Laminated short-linear structures of the subendothelial space were observed in both the TAFRO and POEMS using electron microscopy.nnCONCLUSIONS: Morphological characteristics of the process of renal glomerular damage and repair in TAFRO and POEMS were revealed. The differences in endotheliosis and MPGN-pattern injury in these diseases may reflect differences in the timing of renal biopsy and the clinical course.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41622428,

title = {Gross Intrahepatic Mass Formation Predicts the Primary Site of Perihilar Cholangiocarcinoma Based on Molecular Pathologic Studies},

author = {Yuki Masuda and Naoto Kubota and Ryo Takemura and Yasuhito Arai and Yuta Abe and Osamu Itano and Minoru Esaki and Tatsuhiro Shibata and Yuko Kitagawa and Hidenori Ojima},

doi = {10.1002/jhbp.70077},

issn = {1868-6982},

year  = {2026},

date = {2026-04-01},

journal = {J Hepatobiliary Pancreat Sci},

volume = {33},

number = {4},

pages = {284--293},

abstract = {BACKGROUND/PURPOSE: Intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA) are clinically and genetically distinct. However, the classification of perihilar cholangiocarcinoma (phCCA) with an intrahepatic tumor mass remains unclear. This study aimed to position phCCA near the hilar plate (hCCA) within an extrahepatic-intrahepatic framework using pathological and molecular analyses.nnMETHODS: Among 357 resected invasive CCAs, 100 hCCAs were histologically classified as either hCCA with (hCCA-M) or hCCA without (hCCA-NM) a grossly evident intrahepatic mass. Transcriptomic comparison of 9 typical eCCAs and 39 mass-forming iCCAs identified three contextual markers, which were examined by immunohistochemistry in 309 additional cases.nnRESULTS: Among 100 hCCAs, 85 were hCCA-NM and 15 hCCA-M. Claudin 18 (CLDN18) and mesothelin (MSLN) were identified as extrahepatic contextual markers, and serpin family A member 1 (SERPINA1) as an intrahepatic contextual marker. SERPINA1 was more highly expressed in hCCA-M than in hCCA-NM, regardless of microscopic liver parenchymal invasion, whereas CLDN18 and MSLN were similarly expressed in both. Cluster analysis revealed that hCCA-NM clustered with eCCA, whereas hCCA-M clustered with iCCA.nnCONCLUSIONS: Gross intrahepatic mass formation indicates an intrahepatic contextual profile and provides a useful criterion for subclassifying hCCA. This contextual framework shows that hCCA-M and hCCA-NM represent biologically distinct tumor groups.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41882809,

title = {Spread Through Air Spaces in Colorectal Lung Metastases Signals Local Recurrenece and Reflects Morphologic Aggressiveness of the Primary Tumor},

author = {Taketo Nakai and Satoru Morita and Yutaka Kurebayashi and Masayoshi Monno and Ryo Seishima and Kohei Shigeta and Koji Okabayashi and Mari Mino-Kenudson and Yuko Kitagawa and Keisuke Asakura},

doi = {10.1111/pin.70107},

issn = {1440-1827},

year  = {2026},

date = {2026-03-01},

journal = {Pathol Int},

volume = {76},

number = {3},

pages = {e70107},

abstract = {Tumor spread through air spaces (STAS) is a histological feature associated with poor prognosis in primary lung cancer, but its relevance in colorectal cancer (CRC) pulmonary metastases remains unclear. This study evaluated the prognostic impact of STAS in CRC pulmonary metastases and its association with histologic features of the primary tumor. A total of 124 patients who underwent pulmonary resection for CRC metastases were retrospectively analyzed. Quantitative STAS parameters, including density and maximum spread distance, were assessed histologically. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models, and logistic regression identified predictors of STAS. STAS was present in 33.1% of patients and was associated with significantly shorter 5-year recurrence-free survival (18.7% vs. 53.0%, p = 0.002) and overall survival (p = 0.001). Quantitative STAS metrics correlated with intrathoracic recurrence. Patients with high tumor budding grade had a significantly higher STAS-positive rate than those with none or low grade (60% vs. 31.2%, p = 0.036). Tumor budding independently predicted STAS (odds ratio: 3.19, 95% confidence interval: 1.05-9.69, p = 0.040). STAS independently predicted poor prognosis, particularly intrathoracic recurrence. Quantitative STAS assessment enhanced prognostic precision, and tumor budding grade may serve as a preoperative marker for predicting STAS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41825862,

title = {Multiple pulmonary nodules in a 50-year-old man},

author = {Akinari Atsumi and Hiroki Kabata and Mitsuhiro Akiyama and Yu Okubo and Yutaka Kurebayashi and Hirofumi Kamata and Koichi Fukunaga},

doi = {10.1136/thorax-2025-224602},

issn = {1468-3296},

year  = {2026},

date = {2026-03-01},

journal = {Thorax},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41507565b,

title = {Prognostic model for pancreatic cancer based on machine learning of routine slides and transcriptomic tumor analysis},

author = {Manabu Takamatsu and Mariko Tanaka and Yohei Masugi and Yosuke Inoue and Hiroko Nagano and Tho Ngoc-Quynh Le and Kenji Nishida and Yui Sawa and Kota Sugiura and Yoshikuni Kawaguchi and Yusuke Kazami and Yousuke Nakai and Tsuyoshi Hamada and Tatsunori Suzuki and Kensuke Hara and Yutaka Kurebayashi and Tsuyoshi Takeda and Naoki Sasahira and Yosuke Uematsu and Sho Uemura and Mitsuhiro Fujishiro and Kiyoshi Hasegawa and Minoru Kitago and Yu Takahashi and Shigeki Sekine and Tetsuo Ushiku and Kengo Takeuchi and },

doi = {10.1038/s41416-025-03308-7},

issn = {1532-1827},

year  = {2026},

date = {2026-03-01},

journal = {Br J Cancer},

volume = {134},

number = {6},

pages = {849--859},

abstract = {BACKGROUND: Prognostication for pancreatic ductal adenocarcinoma (PDAC) using histologic images is difficult due to tumor heterogeneity. We developed an artificial intelligence (AI) model to predict postoperative recurrence using histologic image patches.nnMETHODS: We included 591 patients with resected PDAC to train an AI model for recurrence prediction at 12 or 24 months and validated it using external cohorts (n = 302 in total). Image patches from hematoxylin and eosin-stained slides were clustered via uniform manifold approximation and projection (UMAP) and used to train a random forest model. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC). Gene expression analysis was conducted to characterise survival-related clusters.nnRESULTS: Seventeen patch clusters were identified. Two were linked to high recurrence risk, and one to low risk. In external validation, the model achieved an AUC of up to 0.792. The random forest score independently predicted recurrence. Greater heterogeneity in patch composition correlated with shorter time to recurrence (P < 0.01). High-risk clusters showed elevated CSF3R expression; the low-risk cluster showed increased IGFBP3 expression.nnCONCLUSIONS: Our AI model, using only archival histologic slides, accurately predicted postoperative recurrence in PDAC and revealed image features linked to outcomes and gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41507565,

title = {Prognostic model for pancreatic cancer based on machine learning of routine slides and transcriptomic tumor analysis},

author = {Manabu Takamatsu and Mariko Tanaka and Yohei Masugi and Yosuke Inoue and Hiroko Nagano and Tho Ngoc-Quynh Le and Kenji Nishida and Yui Sawa and Kota Sugiura and Yoshikuni Kawaguchi and Yusuke Kazami and Yousuke Nakai and Tsuyoshi Hamada and Tatsunori Suzuki and Kensuke Hara and Yutaka Kurebayashi and Tsuyoshi Takeda and Naoki Sasahira and Yosuke Uematsu and Sho Uemura and Mitsuhiro Fujishiro and Kiyoshi Hasegawa and Minoru Kitago and Yu Takahashi and Shigeki Sekine and Tetsuo Ushiku and Kengo Takeuchi and },

doi = {10.1038/s41416-025-03308-7},

issn = {1532-1827},

year  = {2026},

date = {2026-03-01},

journal = {Br J Cancer},

volume = {134},

number = {6},

pages = {849--859},

abstract = {BACKGROUND: Prognostication for pancreatic ductal adenocarcinoma (PDAC) using histologic images is difficult due to tumor heterogeneity. We developed an artificial intelligence (AI) model to predict postoperative recurrence using histologic image patches.nnMETHODS: We included 591 patients with resected PDAC to train an AI model for recurrence prediction at 12 or 24 months and validated it using external cohorts (n = 302 in total). Image patches from hematoxylin and eosin-stained slides were clustered via uniform manifold approximation and projection (UMAP) and used to train a random forest model. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC). Gene expression analysis was conducted to characterise survival-related clusters.nnRESULTS: Seventeen patch clusters were identified. Two were linked to high recurrence risk, and one to low risk. In external validation, the model achieved an AUC of up to 0.792. The random forest score independently predicted recurrence. Greater heterogeneity in patch composition correlated with shorter time to recurrence (P < 0.01). High-risk clusters showed elevated CSF3R expression; the low-risk cluster showed increased IGFBP3 expression.nnCONCLUSIONS: Our AI model, using only archival histologic slides, accurately predicted postoperative recurrence in PDAC and revealed image features linked to outcomes and gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41636940,

title = {Post-biopsy proteinuria as a universal prognostic marker across diverse clinical courses in IgA nephropathy},

author = {Akihiro Shimizu and Nobuo Tsuboi and Hiroyuki Ueda and Kentaro Koike and Masahiro Okabe and Shinya Yokote and Takaya Sasaki and Keita Hirano and Tetsuya Kawamura and Takashi Yokoo and Yusuke Suzuki and },

doi = {10.1007/s10157-025-02808-3},

issn = {1437-7799},

year  = {2026},

date = {2026-03-01},

journal = {Clin Exp Nephrol},

volume = {30},

number = {3},

pages = {498--506},

abstract = {BACKGROUND: Although proteinuria is a key prognostic marker in immunoglobulin A nephropathy (IgAN), the optimal post-biopsy timing for its assessment remains uncertain, particularly given variability in treatment type and timing. Using longitudinal data from the Japan IgA Nephropathy Prospective Cohort Study (J-IGACS), we sought to identify the post-biopsy time point at which proteinuria most reliably predicts kidney outcomes.nnMETHODS: Proteinuria was assessed at baseline and at 6, 12, 18, and 24 months after biopsy. The primary outcome was defined as a ≥ 50% increase in serum creatinine or initiation of kidney replacement therapy in adults (≥ 20 years) and as a ≥ 25% decline in eGFR or initiation of kidney replacement therapy in patients aged < 20 years. Model performance was compared using the corrected Akaike Information Criterion.nnRESULTS: Among 588 patients (median age 38 years; mean eGFR 76.5 mL/min/1.73 m; median proteinuria 0.64 g/day), 43 (7.3%) reached the primary outcome during a median 78-month follow-up. Proteinuria at all time points was independently associated with kidney outcomes, with the 18-month measurement providing the best model fit. A threshold of 0.44 g/day (or g/gCr) yielded 79% sensitivity and 81% specificity, and patients with proteinuria ≥ 0.44 g/day at 18 months had significantly worse outcomes. Cox regression confirmed a robust association for 18-month proteinuria, irrespective of treatment type or timing.nnCONCLUSIONS: Proteinuria measured 18 months post-biopsy showed the strongest association with long-term kidney outcomes in IgAN, supporting its use as a universal treatment target across heterogeneous post-biopsy clinical courses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41051966,

title = {Association between Urinary Fractional Excretion of Potassium and Proteinuria Remission in Adult Nephrotic Syndrome},

author = {Ryuto Yoshida and Takashin Nakayama and Ryunosuke Mitsuno and Motoaki Komatsu and Yoichi Oshima and Seiei Iwabuchi and Tomoaki Itoh and Dai Matsumoto and Ei Kusahana and Kenta Hoshi and Kyosei Nakamura and Kentaro Fujii and Yoshikazu Hara and Takahisa Kawaguchi and Koji Futatsugi and Yasuyoshi Yamaji and Hirobumi Tokuyama and Marohito Murakami and Chie Takimoto and Hiroto Matsuda and Takashi Ando and Akinori Hashiguchi and Yuko Kaneko and Tatsuhiko Azegami and Kaori Hayashi},

doi = {10.34067/KID.0000000997},

issn = {2641-7650},

year  = {2026},

date = {2026-03-01},

journal = {Kidney360},

volume = {7},

number = {3},

pages = {624--632},

abstract = {KEY POINTS: Elevated fractional excretion of potassium (FEK) at biopsy predicts a lower rate of proteinuria remission in adults with nephrotic syndrome. FEK levels vary by histologic types, being low in minimal change disease and high in diabetic kidney disease, suggesting diagnostic utility. FEK shows a dose-dependent link with remission, supporting its use as a simple prognostic biomarker.nnBACKGROUND: Reliable prognostic biomarkers of nephrotic syndrome (NS) are crucial for optimizing patient management. The fractional excretion of potassium (FEK) reflects net tubular potassium handling, but its association with prognosis in NS remains unexplored. We aimed to investigate the association between baseline FEK and proteinuria remission in adult NS.nnMETHODS: This multicenter retrospective cohort study was conducted across nine institutions in Japan. We enrolled adult patients diagnosed with NS who underwent a native kidney biopsy and had FEK between January 2012 and June 2022. Patients were categorized based on FEK levels and followed until the first complete remission of proteinuria.nnRESULTS: A total of 401 patients (median age, 61 years; 43% female) were included. Study participants were stratified into two groups based on the FEK cutoff value of 10%. Patients with high FEK had a significantly lower cumulative incidence of complete remission compared with those with low FEK ( P < 0.001, log-rank test). In multivariable Cox regression analysis, high FEK was independently associated with a lower likelihood of complete remission (hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.78). The trend of this association was observed across most subgroups, including those based on histologic diagnosis of minimal change disease and non-minimal change disease. Further stratification into four FEK categories revealed a progressive decline in remission rates with increasing FEK, indicating a dose-dependent relationship.nnCONCLUSIONS: Elevated FEK is an independent predictor of a lower likelihood of proteinuria remission in Japanese adults with NS. FEK may serve as a readily accessible and valuable prognostic biomarker in the clinical management of NS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41266845,

title = {Predictors of lymph node metastases, recurrence, and survival in patients with pedunculated-type T1 colorectal cancer},

author = {Kengo Kasuga and Toshio Uraoka and Yoshiki Kajiwara and Shiro Oka and Shinji Tanaka and Takahiro Nakamura and Shoichi Saito and Yosuke Fukunaga and Manabu Takamatsu and Hiroshi Kawachi and Kinichi Hotta and Hiroaki Ikematsu and Motohiro Kojima and Yutaka Saito and Yukihide Kanemitsu and Shigeki Sekine and Shinji Nagata and Kazutaka Yamada and Jun Konishi and Soichiro Ishihara and Yusuke Saitoh and Kenji Matsuda and Kazutomo Togashi and Koji Komori and Megumi Ishiguro and Toshio Kuwai and Takashi Okuyama and Akihiro Ohuchi and Shinobu Ohnuma and Kazuhiro Sakamoto and Tamotsu Sugai and Kenji Katsumata and Hiro-O Matsushita and Hiro-O Yamano and Keisuke Nakai and Naohiko Akimoto and Hirotoshi Kobayashi and Yoichi Ajioka and Kenichi Sugihara and Hideki Ueno},

doi = {10.1007/s00535-025-02318-9},

issn = {1435-5922},

year  = {2026},

date = {2026-02-01},

journal = {J Gastroenterol},

volume = {61},

number = {2},

pages = {172--183},

abstract = {OBJECTIVES: The oncologic outcomes of pedunculated-type T1 colorectal cancer (CRC) remain unknown. We determined the risk factors for lymph node metastasis (LNM) and recurrence and evaluated the survival according to the treatment method.nnMETHODS: In this multicenter retrospective study involving 4673 patients with T1 CRC, we analyzed 444 patients with pedunculated-type T1 CRC treated between 2009 and 2016. Treatment included local resection (LR) alone (n = 169), surgery with lymph node (LN) dissection alone (n = 83), and LR followed by additional surgery with LN dissection (n = 192). Factors associated with LNM and recurrence, relapse-free survival (RFS) and overall survival (OS) by treatment were analyzed. The median follow-up period was 64 months.nnRESULTS: LNM and recurrence were observed in 25 (5.6%) and 13 (2.9%) cases, respectively. Submucosal invasion depth ≥ 1000 μm (p = 0.0036), positive lymphovascular invasion (p = 0.0007), and budding grade 2/3 (p = 0.0171) were risk factors for LNM. The risk factor for recurrence was tumor size ≥ 20 mm (HR 5.488; 95% CI 1.199-25.12; p = 0.028) in a multivariate analysis. The 5-year RFS rates were 92.5% for LR alone, 94.3% for LR+ surgery, and 90.5% for surgery alone; the 5-year OS rates were 93.1%, 97.1%, and 94.0%, respectively, with no significant difference.nnCONCLUSION: Even in the specific subset of pedunculated-type T1 CRC, submucosal invasion depth ≥ 1000 μm and budding grade 2/3 are risk factors for LNM. Tumors ≥ 20 mm require careful surveillance for recurrence risk. High RFS and OS rates in LR-alone and LR+ surgery groups suggest LR is appropriate for pedunculated lesions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41629477,

title = {Comparison of Oxford versus Japanese Histological Grading to predict renal function decline in IgA nephropathy: a Japanese prospective cohort study},

author = {Ryoko Sakaguchi and Kensuke Joh and Shiko Honma and Akira Shimizu and Akinori Hashiguchi and Ritsuko Katafuchi and Masako Nishikawa and Kentaro Koike and Keita Hirano and Nobuo Tsuboi and Tetsuya Kawamura and Takashi Yokoo and Yusuke Suzuki},

doi = {10.1038/s41598-026-37412-2},

issn = {2045-2322},

year  = {2026},

date = {2026-02-01},

journal = {Sci Rep},

volume = {16},

number = {1},

pages = {6995},

abstract = {The Oxford (split) and Japanese Histological Grade (JHG [lumped]) classifications of immunoglobulin A nephropathy (IgAN) are widely used in Japan. We compared their prognostic ability and explored the benefits of combining them. Data were from a prospective IgAN cohort (2005–2015). The primary endpoint was a ≥ 50% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. Cox regression with Uno C assessed prognostic discrimination. The integrated discrimination improvement index evaluated the added value of histologic to clinical variables (eGFR, urinary protein, and mean arterial pressure) at 1, 5, and 10 years. Kaplan–Meier analysis stratified patients into JHG 1 and 2–4 to assess the prognostic value of mesangial hypercellularity (M) and interstitial fibrosis/tubular atrophy (T). Among 938 patients (median follow-up: 66 months), 58 (6.2%) reached the endpoint. M and T (Oxford) and JHG were significantly associated with outcomes. Both systems showed good discrimination (Uno C: 0.83 and 0.86). Adding Oxford to clinical variables improved prediction at 5 and 10 years; adding JHG improved prediction at 1, 5, and 10 years. M and T were predictive in JHG 2–4 but not in JHG 1. Both classifications demonstrated comparable discrimination. Their combined use can help enhance predictive precision.nnSUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37412-2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41502805,

title = {Supportive Evidence of Surrogate End Points Based on Treatment Effect of Corticosteroid in IgA Nephropathy},

author = {Takaya Sasaki and Nobuo Tsuboi and Kentaro Koike and Hiroyuki Ueda and Masahiro Okabe and Shinya Yokote and Akihiro Shimizu and Keita Hirano and Tetsuya Kawamura and Takashi Yokoo and Yusuke Suzuki and },

doi = {10.1016/j.ekir.2025.09.002},

issn = {2468-0249},

year  = {2026},

date = {2026-02-01},

journal = {Kidney Int Rep},

volume = {11},

number = {2},

pages = {103588},

abstract = {INTRODUCTION: Estimated glomerular filtration rate (eGFR) slope and proteinuria reduction have been proposed as surrogate end points for kidney outcomes in IgA nephropathy (IgAN), but their validity remains under debate. We aimed to evaluate the surrogate potential of these markers in the context of corticosteroid therapy within a large Japanese cohort.nnMETHODS: Patients with biopsy-proven IgAN from the Japan IgA Nephropathy Cohort Study were analyzed. Patients were categorized based on corticosteroid exposure within 12 months of diagnosis. To minimize confounding, overlap weighting was used to balance baseline characteristics. The primary outcome was a composite kidney end point defined as a ≥ 40 decline in eGFR or the initiation of kidney replacement therapy. Secondary outcomes included 2-year eGFR slope and proteinuria reduction at 1-year.nnRESULTS: Corticosteroid therapy was associated with a lower incidence of the composite kidney outcome (5.3 vs. 13.1%,  = 0.0485), slower decline in eGFR (-0.32 vs. -2.95 ml/min per 1.73 m/yr,  = 0.01), and greater proteinuria reduction (-76.5% vs. -48.0%,  < 0.001).nnCONCLUSION: Both the eGFR slope and proteinuria reduction demonstrated strong and consistent associations with kidney outcomes in the context of corticosteroid therapy. These findings support their effectiveness as surrogate end points for clinical trials and suggest their usefulness for risk stratification and therapeutic monitoring in routine nephrology practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41201548,

title = {Real-world comparison between neoadjuvant FLOT therapy and DCF therapy for resectable esophagogastric junction adenocarcinoma},

author = {Kazuhiro Shiraishi and Shun Yamamoto and Toshiharu Hirose and Hiroshi Imazeki and Kazuki Yokoyama and Yoshitaka Honma and Taiki Hashimoto and Tairo Kashihara and Daisuke Kurita and Koshiro Ishiyama and Junya Oguma and Hiroshi Igaki and Hiroyuki Daiko and Yasuyuki Seto and Ken Kato},

doi = {10.1007/s10388-025-01168-x},

issn = {1612-9067},

year  = {2026},

date = {2026-01-01},

journal = {Esophagus},

volume = {23},

number = {1},

pages = {201--210},

abstract = {BACKGROUNDS: In Western countries, the standard perioperative treatment for resectable locally advanced esophagogastric junction adenocarcinoma (EGJ-AC) is 5-fluorouracil, oxaliplatin, and docetaxel (FLOT) therapy based on the results of the FLOT4 and ESOPEC trials. On the other hand, there was little evidence based on optimal perioperative treatment for resectable locally advanced EGJ-AC in Japan. Our previous report showed that neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy demonstrated modest efficacy for resectable locally advanced EGJ-AC. Therefore, we compared neoadjuvant DCF to FLOT therapy in terms of efficacy and safety in this study.nnMETHODS: We retrospectively analyzed the data of patients who received DCF or FLOT therapy for resectable EGJ-AC between 2015 and 2024 in our hospital. We assessed the R0 resection rate, histopathological response, disease-free survival (DFS), overall survival, and adverse events.nnRESULTS: Thirty-two patients in the DCF therapy group and 20 patients in the FLOT therapy group were analyzed. The patients' characteristics in the DCF group and FLOT group were as follows: median age, 63/59 years; ECOG PS 0, 66%/85%, respectively. The pCR rate was numerically higher in the FLOT group (20%) compared with the DCF group (3%) (p = 0.07). Similarly, the 1-year DFS rate was higher in the FLOT group (93%) than in the DCF group (68%) (p = 0.02), although this difference did not remain statistically significant after adjustment for baseline factors. Febrile neutropenia was significantly lower in the FLOT group (0%) than in the DCF group (12.5%).nnCONCLUSIONS: Neoadjuvant FLOT therapy is well-tolerated and has comparable short-term efficacy to DCF therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41085951,

title = {Safety and short-term efficacy of neoadjuvant FLOT therapy in cisplatin-unfit patients with resectable esophageal squamous cell carcinoma},

author = {Yuri Yoshinami and Shun Yamamoto and Kazuhiro Shiraishi and Hiroshi Imazeki and Kazuki Yokoyama and Yoshitaka Honma and Daisuke Kurita and Koshiro Ishiyama and Junya Oguma and Taiki Hashimoto and Tairo Kashihara and Hiroyuki Daiko and Ken Kato},

doi = {10.1007/s10388-025-01160-5},

issn = {1612-9067},

year  = {2026},

date = {2026-01-01},

journal = {Esophagus},

volume = {23},

number = {1},

pages = {167--173},

abstract = {BACKGROUNDS: The standard neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) is a combination of docetaxel, cisplatin (CDDP), and 5-fluorouracil in Japan. However, patients with renal or cardiac dysfunction and elderly patients were unfit for CDDP-containing regimens due to toxicity. In this context, 5-fluorouracil and leucovorin, oxaliplatin, docetaxel (FLOT) therapy, which is the standard neoadjuvant therapy for esophagogastric adenocarcinoma in Western countries, offers an alternative that can be administered to the patients who are unfit for CDDP. However, the safety and short-term efficacy of neoadjuvant FLOT therapy in patients with LA-ESCC remain unclear.nnMATERIALS AND METHODS: This retrospective study analyzed patients with resectable LA-ESCC who received neoadjuvant FLOT from February 2021 to December 2023. Four cycles of FLOT were administered every 2 weeks, and then the subjects underwent esophagectomy. Adverse events were evaluated according to the CTCAE version 5.0, and pathological response and survival outcomes were evaluated for efficacy.nnRESULTS: Forty-six patients were included in this study. Median age was 76 years (range 57-84 years). Clinical stage III and IVB were the most frequent, at 61% and 20%, respectively. During the neoadjuvant therapy, the most common grade 3 or higher adverse events were neutropenia (65%) and leukopenia (50%). Of 36 patients who underwent surgery, pathologic complete response (ypT0N0) was observed in 5 patients (13.9%). The median progression-free survival and overall survival were 15.0 and 25.2 months, respectively.nnCONCLUSIONS: Neoadjuvant FLOT demonstrated manageable safety profiles and promising efficacy in patients with resectable LA-ESCC who were CDDP-unfit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41222477,

title = {T-cell Subset Features and Distributions Evolve across the Colorectal Precancer-Cancer Spectrum},

author = {Yasutoshi Takashima and Andressa Dias Costa and Naohiko Akimoto and Tomotaka Ugai and Phoenix Bell and Juha P Väyrynen and Jason L Hornick and Mari Mino-Kenudson and Yuxue Zhong and Satoko Ugai and Koichiro Haruki and Qian Yao and Kosuke Matsuda and Mayu Higashioka and Daniel D Buchanan and Amanda I Phipps and Ulrike Peters and Marios Giannakis and Mingyang Song and Andrew T Chan and Charles S Fuchs and Jonathan A Nowak and Shuji Ogino},

doi = {10.1158/2326-6066.CIR-25-0481},

issn = {2326-6074},

year  = {2026},

date = {2026-01-01},

journal = {Cancer Immunol Res},

volume = {14},

number = {1},

pages = {46--59},

abstract = {The immune microenvironment is a crucial component of colorectal carcinoma that has been well characterized, but much less is known about the immune microenvironment of colorectal carcinoma precursors. We hypothesized that T-cell infiltrates might differ across the colorectal neoplastic spectrum. We leveraged the prospective cohort incident-tumor biobank method, which provided formalin-fixed, paraffin-embedded tumor tissue specimens (N = 1,825) from 790 colorectal carcinoma precursors (including hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, tubular adenomas, tubulovillous adenomas, and villous adenomas) and 1,035 colorectal carcinomas. We performed an in situ multispectral immunofluorescence assay for CD3, CD4, CD8, FOXP3 (negative, low, or high expression), PTPRC (CD45RO and CD45RA), MKI67 (Ki-67), and KRT (keratin) combined with supervised machine learning. CD3+CD4+ cells were more abundant than CD3+CD8+ cells in most precursors. In conventional adenomas, greater villous component correlated with fewer intraepithelial CD3+CD8+ cells. Serrated lesions, including hyperplastic polyps and sessile serrated lesions, exhibited higher densities of intraepithelial CD3+CD8+ cells compared with other precursors and carcinomas. Age strata of patients with precursors (including early-onset precursors) were not associated with differential T-cell infiltration patterns. Compared with invasive colorectal carcinoma, precursors generally showed higher densities of CD3+CD4+ cells and CD3+CD8+ cells with phenotypes of naive (CD45RA+CD45RO-), memory (CD45RA-CD45RO+), and regulatory (FOXP3+Low and FOXP3+High) in intraepithelial and lamina propria/stromal regions. In conclusion, T-cell infiltration patterns vary across different histopathologic types of the colorectal neoplastic spectrum from precursors to invasive carcinomas. Our findings shed light on how the tumor-immune microenvironment evolves during precursor development and progression to colorectal carcinoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41549214,

title = {Plasma Fibrinogen Predicts Response to Immune Checkpoint Inhibitor by Inflammatory Tumor Microenvironment in Esophageal Cancer},

author = {Keiso Ho and Satoru Matsuda and Eisuke Booka and Wataru Soneda and Jun Okui and Shota Hoshino and Masashi Takeuchi and Kazumasa Fukuda and Sara Horie and Yuki Saito and Yasunori Kogure and Hirofumi Kawakubo and Kensuke Hara and Hajime Okita and Keisuke Kataoka and Shigeki Sekine and Hiroya Takeuchi and Yuko Kitagawa},

doi = {10.1002/cam4.71548},

issn = {2045-7634},

year  = {2026},

date = {2026-01-01},

journal = {Cancer Med},

volume = {15},

number = {1},

pages = {e71548},

abstract = {BACKGROUND: Plasma fibrinogen (FNG) is a prognostic marker in esophageal squamous cell carcinoma (ESCC). However, its predictive value for immune checkpoint inhibitor (ICI) efficacy and the underlying mechanisms remain unclear. This study aimed to evaluate the clinical significance of plasma FNG levels in ICI-treated ESCC patients and investigate its association with tumor-associated neutrophils (TANs) and genomic alterations.nnMETHODS: A retrospective, multicenter analysis of 167 ESCC patients treated with ICIs was performed. TANs were quantified via immunohistochemistry using CD11b and CD66b staining, and PD-L1 expression was assessed using the tumor proportion score (TPS). Whole-exome and RNA sequencing were conducted to analyze genomic and transcriptomic profiles.nnRESULTS: Elevated plasma FNG levels correlated with lower ICI response rates and decreased survival. In first-line treatment, chemo-ICI therapy demonstrated superior efficacy compared to dual-ICI therapy in high-FNG patients, while the reverse trend was observed in low-FNG patients. High-FNG tumors showed increased TAN infiltration, independent of PD-L1 expression. RNA sequencing revealed enrichment of neutrophil activation and extravasation pathways in high-FNG tumors.nnCONCLUSIONS: Elevated plasma FNG levels predict poor prognosis and reduced ICI efficacy in ESCC. They may be potential biomarkers for first-line ICI-based therapy and correlate with TAN infiltration. Further validation and mechanistic investigations are warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41214301,

title = {Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer},

author = {Kohji Tanakaya and Tatsuro Yamaguchi and Keiji Hirata and Masayoshi Yamada and Kensuke Kumamoto and Yasuki Akiyama and Kei Ishimaru and Koichi Okamoto and Yuko Kawasaki and Keigo Komine and Akira Sakamoto and Kunitoshi Shigeyasu and Yoshiko Shibata and Yusaku Shimamoto and Hideki Shimodaira and Shigeki Sekine and Akinari Takao and Misato Takao and Yasuyuki Takamizawa and Yoji Takeuchi and Noriko Tanabe and Fumitaka Taniguchi and Akiko Chino and Hourin Cho and Satoru Doi and Takeshi Nakajima and Sakiko Nakamori and Yoshiko Nakayama and Toshiya Nagasaki and Hisashi Hasumi and Kouji Banno and Takao Hinoi and Kenji Fujiyoshi and Takahiro Horimatsu and Kenta Masuda and Masashi Miguchi and Yusuke Mizuuchi and Yasuyuki Miyakura and Michihiro Mutoh and Takahiro Yoshioka and Shinji Tanaka and Kazuhiro Sakamoto and Kentaro Sakamaki and Michio Itabashi and Hideyuki Ishida and Naohiro Tomita and Kenichi Sugihara and Yoichi Ajioka and },

doi = {10.1007/s10147-025-02892-1},

issn = {1437-7772},

year  = {2026},

date = {2026-01-01},

journal = {Int J Clin Oncol},

volume = {31},

number = {1},

pages = {1--66},

abstract = {Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40987948,

title = {Urine-to-blood urea nitrogen ratio predicts proteinuria remission in nephrotic syndrome},

author = {Ryunosuke Mitsuno and Takashin Nakayama and Ryuto Yoshida and Motoaki Komatsu and Yoichi Oshima and Seiei Iwabuchi and Kenta Hoshi and Tomoaki Itoh and Dai Matsumoto and Kentaro Fujii and Yoshikazu Hara and Koji Futatsugi and Takahisa Kawaguchi and Takashi Ando and Hiroto Matsuda and Yasuyoshi Yamaji and Marohito Murakami and Jun Yoshino and Akinori Hashiguchi and Yuko Kaneko and Tatsuhiko Azegami and Kaori Hayashi},

doi = {10.1007/s10157-025-02771-z},

issn = {1437-7799},

year  = {2026},

date = {2026-01-01},

journal = {Clin Exp Nephrol},

volume = {30},

number = {1},

pages = {109--116},

abstract = {BACKGROUND: Nephrotic syndrome (NS) carries a high risk of severe complications and kidney failure, necessitating reliable prognostic markers. Given the link between tubular injury and poor remission of proteinuria, markers of tubular function may be informative in NS. The urine-to-blood urea nitrogen ratio (UBUR) reflects tubular urea handling, yet its prognostic value in NS is unclear. We evaluated whether baseline UBUR predicts proteinuria remission in adult NS.nnMETHODS: This multicenter retrospective study included patients with NS who underwent kidney biopsy between January 2012 and June 2022. Patients were followed from kidney biopsy until complete remission, dialysis initiation, death, or the end of the observation period (12 months after kidney biopsy).nnRESULTS: A total of 237 patients (median age, 63 years; 47% female) were included, and divided into two groups based on a UBUR cutoff of 25.4 determined by the receiver operating characteristic curve. Patients with high UBUR had a significantly higher cumulative incidence of complete remission compared to those with low UBUR (P < 0.001, log-rank test). In multivariable Cox regression analysis, high UBUR independently predicted a greater likelihood of complete remission (hazard ratio 2.30 [95% confidence interval 1.47-3.61]). This association persisted in the subgroup analyses for podocytopathies, defined as minimal change disease and focal segmental glomerulosclerosis.nnCONCLUSIONS: High UBUR independently predicts proteinuria remission in adults with NS. UBUR could have potential as a simple, valuable biomarker to help guide the management of NS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39937126,

title = {Long-term yogurt intake and colorectal cancer incidence subclassified by  abundance in tumor},

author = {Satoko Ugai and Li Liu and Keisuke Kosumi and Hidetaka Kawamura and Tsuyoshi Hamada and Kosuke Mima and Kota Arima and Kazuo Okadome and Qian Yao and Kosuke Matsuda and Yuxue Zhong and Hiroki Mizuno and Andrew T Chan and Wendy S Garrett and Mingyang Song and Marios Giannakis and Edward L Giovannucci and Xuehong Zhang and Shuji Ogino and Tomotaka Ugai},

doi = {10.1080/19490976.2025.2452237},

issn = {1949-0984},

year  = {2025},

date = {2025-12-01},

journal = {Gut Microbes},

volume = {17},

number = {1},

pages = {2452237},

abstract = {Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains . We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue . We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by the abundance of tumor tissue . During follow-up of 132,056 individuals, we documented 3,079 incident colorectal cancer cases, including 1,121 with available tissue  data. The association between long-term yogurt intake and colorectal cancer incidence differed by  abundance (P heterogeneity = 0.0002). Multivariable-adjusted hazard ratios (HRs) (with 95% confidence intervals) in individuals who consumed ≥2 servings/week (vs. <1 serving/month) of yogurt were 0.80 (0.50-1.28) for -positive tumor and 1.09 (0.81-1.46) for -negative tumor. This differential association was also observed in a subgroup analysis of proximal colon cancer (P heterogeneity = 0.018). Long-term yogurt intake may be differentially associated with the incidence of proximal colon cancer according to  abundance, suggesting the antitumor effect of yogurt intake on the specific tumor subgroup.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41213665b,

title = {Human chorionic gonadotropin-positive cystic duct carcinoma with trophoblastic differentiation that exhibited an aggressive clinical course},

author = {Yusuke Takemura and Kosuke Matsuda and Yuta Abe and Akinori Hashiguchi and Minoru Kitago and Yutaka Nakano and Keita Sonoda and Yuko Kitagawa},

doi = {10.1136/bcr-2025-266085},

issn = {1757-790X},

year  = {2025},

date = {2025-11-01},

journal = {BMJ Case Rep},

volume = {18},

number = {11},

abstract = {A man in his 60s diagnosed with perihilar cholangiocarcinoma underwent radical surgery. CT on postoperative day 26 showed multiple liver metastases in the remnant liver that rapidly grew and spread to the entire liver. The patient died 70 days following surgery due to highly aggressive tumour progression. In the surgical specimen, the tumour at the margin was histologically identified as predominantly conventional adenocarcinoma, but a few components of the invasive carcinoma and liver metastasis exhibited significant nuclear atypia and rich cytoplasm. The autopsy revealed human chorionic gonadotropin (hCG)-positive multinucleated tumour cells like syncytiotrophoblast with haemorrhage at the metastatic sites in the liver, which finally diagnosed with cystic duct carcinoma with trophoblastic differentiation. hCG-positive carcinomas with trophoblastic differentiation generally carry poor prognoses. For those with significant nuclear atypia and rich cytoplasms with haemorrhage, additional immunostaining for hCG and progression to trophoblastic differentiation should be considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41079974,

title = {Quantification-based explainable artificial intelligence for deep learning decisions: clustering and visualization of quantitative morphometric features in hepatocellular carcinoma discrimination},

author = {Gen Takagi and Saori Takeyama and Tokiya Abe and Akinori Hashiguchi and Michiie Sakamoto and Kenji Suzuki and Masahiro Yamaguchi},

doi = {10.1117/1.JMI.12.6.061407},

issn = {2329-4302},

year  = {2025},

date = {2025-11-01},

journal = {J Med Imaging (Bellingham)},

volume = {12},

number = {6},

pages = {061407},

abstract = {PURPOSE: Deep learning (DL) is rapidly advancing in computational pathology, offering high diagnostic accuracy but often functioning as a "black box" with limited interpretability. This lack of transparency hinders its clinical adoption, emphasizing the need for quantitative explainable artificial intelligence (QXAI) methods. We propose a QXAI approach to objectively and quantitatively elucidate the reasoning behind DL model decisions in hepatocellular carcinoma (HCC) pathological image analysis.nnAPPROACH: The proposed method utilizes clustering in the latent space of embeddings generated by a DL model to identify regions that contribute to the model's discrimination. Each cluster is then quantitatively characterized by morphometric features obtained through nuclear segmentation using HoverNet and key feature selection with LightGBM. Statistical analysis is performed to assess the importance of selected features, ensuring an interpretable relationship between morphological characteristics and classification outcomes. This approach enables the quantitative interpretation of which regions and features are critical for the model's decision-making, without sacrificing accuracy.nnRESULTS: Experiments on pathology images of hematoxylin-and-eosin-stained HCC tissue sections showed that the proposed method effectively identified key discriminatory regions and features, such as nuclear size, chromatin density, and shape irregularity. The clustering-based analysis provided structured insights into morphological patterns influencing classification, with explanations evaluated as clinically relevant and interpretable by a pathologist.nnCONCLUSIONS: Our QXAI framework enhances the interpretability of DL-based pathology analysis by linking morphological features to classification decisions. This fosters trust in DL models and facilitates their clinical integration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41145733,

title = {Clinical utility of comprehensive genomic profiling versus Oncomine Dx target test in pathological stage II-III non-small cell lung cancer},

author = {Kaito Yano and Kaoru Kaseda and Kohei Nakamura and Yu Okubo and Kyohei Masai and Tomoyuki Hishida and Shigenari Nukaga and Keiko Ohgino and Hideki Terai and Hiroyuki Yasuda and Yutaka Kurebayashi and Koichi Fukunaga and Hiroshi Nishihara and Keisuke Asakura},

doi = {10.1038/s41598-025-21559-5},

issn = {2045-2322},

year  = {2025},

date = {2025-10-01},

journal = {Sci Rep},

volume = {15},

number = {1},

pages = {37477},

abstract = {The next-generation sequencing (NGS)-based Oncomine Dx Target Test (ODxTT) is the standard tool for guiding postoperative adjuvant therapy in patients with non-small cell lung cancer (NSCLC) in Japan. To advance precision oncology, we evaluated the clinical utility of an in-house comprehensive genomic profiling (CGP) assay, Rapid-Neo, as a complementary approach to ODxTT in surgically resected NSCLC. Patients with pathological stage II-III NSCLC who underwent anatomical surgical resection between December 2019 and May 2024 were included. Resected specimens underwent genomic analysis using both ODxTT and Rapid-Neo CGP. We evaluated the mutational concordance and the frequency of additional actionable alterations identified by CGP. Among 68 eligible patients, driver mutation results were concordant in 64 (94.1%) cases. Crucially, CGP rescued one patient for targeted therapy by detecting an EGFR mutation where ODxTT failed due to insufficient DNA. CGP also identified rare EGFR variants not covered by ODxTT in two cases, although it failed to detect a RET fusion in one patient. Furthermore, CGP revealed additional actionable alterations, such as tumor suppressor gene mutations, in 57 patients (83.8%). Our in-house CGP shows high concordance with ODxTT and serves as a powerful complementary tool. These findings support a strategic testing algorithm where CGP is incorporated for patients with negative or inconclusive ODxTT results, or at the time of recurrence, to maximize opportunities for individualized therapy in resected NSCLC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40884897,

title = {Lineage-specific transcription factor landscape of thymic neuroendocrine tumors},

author = {Seiji Omura and Yutaka Kurebayashi and Junko Hamamoto and Hideki Terai and Tomohiro Imoto and Mikito Suzuki and Kazuo Nakagawa and Takahiro Suzuki and Takao Shigenobu and Akira Yoshizu and Chihaya Maeda and Masahiro Kaji and Yu Okubo and Shigeki Suzuki and Kyohei Masai and Kaoru Kaseda and Koichi Fukunaga and Hiroyuki Yasuda and Keisuke Asakura},

doi = {10.1016/j.lungcan.2025.108731},

issn = {1872-8332},

year  = {2025},

date = {2025-10-01},

journal = {Lung Cancer},

volume = {208},

pages = {108731},

abstract = {INTRODUCTION: Thymic neuroendocrine tumors (TNETs) are rare malignancies characterized by aggressive clinical behavior and limited therapeutic options. In small cell lung cancer (SCLC), molecular subtypes based on the expression of lineage-defining transcription factors (TFs)-ASCL1, NEUROD1, POU2F3, and YAP1-have been proposed. However, the TF landscape of TNETs remains poorly defined. Given the pathological similarities among neuroendocrine tumors across organs, we aimed to investigate whether the TF-based classification system used in SCLC is applicable to TNETs.nnMETHODS: Sixteen pathologically confirmed TNETs-including large cell neuroendocrine carcinoma (LCNEC), thymic small cell carcinoma (TSCC), atypical carcinoid (AC), and typical carcinoid (TC)-were retrospectively analyzed. Immunohistochemistry was performed to evaluate classical neuroendocrine (NE) markers (synaptophysin, chromogranin A, CD56) and TFs (ASCL1, NEUROD1, POU2F3, YAP1). H-scores were calculated, and tumors were categorized according to TFs expression profiles.nnRESULTS: Synaptophysin was strongly expressed in all cases, while chromogranin A and CD56 showed variable expression, with reduced levels in LCNEC and TSCC. The combined NE score was significantly higher in carcinoid tumors compared to LCNEC and TSCC. For TFs, ASCL1 expression was observed in 93.8 % of cases, whereas NEUROD1 and POU2F3 were rarely or not expressed. YAP1 expression was confined to LCNEC cases, all of which co-expressed ASCL1 and YAP1. Based on H-scores, TNETs were classified into three subgroups: (1) ASCL1-positive/YAP1-negative (n = 12, 75 %), (2) ASCL1/YAP1 double-positive (n = 3, 19 %), and (3) double-negative (n = 1, 6 %).nnCONCLUSION: This study reveals molecular heterogeneity among TNETs. Notably, ASCL1 and YAP1 co-expression characterizes all LCNEC cases, making a distinct TF landscape in high-grade TNETs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40757605,

title = {Clinical Application of In-House Comprehensive Genomic Profiling for Thoracic Cancer: Insights From a Japanese Hospital},

author = {Hatsuyo Takaoka and Hideki Terai and Kohei Nakamura and Takaaki Mizuno and Ryutaro Kawano and Katsura Emoto and Yutaka Kurebayashi and Nao Takada and Kenta Hamabe and Kazuhito Horie and Akihiko Ogata and Katsuhito Kinoshita and Lisa Shigematsu and Fumimaro Ito and Masahiko Okada and Takahiro Fukushima and Shigenari Nukaga and Testuo Tani and Keiko Ohgino and Kaoru Kaseda and Shinnosuke Ikemura and Hiroyuki Yasuda and Keisuke Asakura and Hajime Okita and Hiroshi Nishihara and Koichi Fukunaga},

doi = {10.1111/cas.70168},

issn = {1349-7006},

year  = {2025},

date = {2025-10-01},

journal = {Cancer Sci},

volume = {116},

number = {10},

pages = {2819--2830},

abstract = {Comprehensive genomic profiling (CGP) is useful for optimizing targeted therapy and immunotherapy strategies for thoracic malignancies. This study aimed to evaluate the clinical utility and diagnostic complementarity of the in-house sequencing platform Rapid-Neo. We retrospectively analyzed 110 patients with thoracic malignancies who underwent Rapid-Neo testing. The baseline characteristics, sequencing results, concordance with companion diagnostics (CDx), and clinical outcomes were assessed. Of 110 patients, 100 (90.9%) had primary lung cancer. Rapid-Neo identified at least one genomic alteration in 99.1% of cases and well-established driver alterations in 66.0% of lung cancer cases. TMB-high and MSI-high statuses were observed in 9.0% and 2.0% of cases, respectively. Among the 90 cases with prior CDx, Rapid-Neo identified driver alterations in 10.0% of the cases, including EGFR, KRAS, MET, RET, and ERBB2, suggesting its potential to overcome the limitations of conventional CDx tests. High concordance (96.8%) was observed between the Rapid-Neo and CDx results, finally. In EGFR-mutant lung adenocarcinoma, high tumor mutation burden (TMB) was associated with a significantly shorter progression-free survival (PFS) after EGFR-TKI therapy (HR = 2.58, p = 0.018) and remained an independent prognostic factor in multivariate analysis. Furthermore, among patients receiving immune checkpoint inhibitors (ICIs), favorable genomic markers such as TMB-high or MSI-high were associated with prolonged PFS. Rapid-Neo demonstrated high sensitivity and concordance with CDx, while also identifying actionable driver alterations missed by the initial CDx. Moreover, the genomic markers identified by Rapid-Neo may provide predictive values for both targeted therapy and immunotherapy responses, supporting their integration into routine clinical decision-making.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41124284,

title = {Conversion of pathogenic T cells into functionally stabilized T cells for antigen-specific immunosuppression in pemphigus vulgaris},

author = {Miho Mukai and Hayato Takahashi and Yoko Kubo and Yasuhiko Asahina and Hisato Iriki and Hisashi Nomura and Aki Kamata and Hiromi Ito and Yutaka Kurebayashi and Jun Yamagami and Norihisa Mikami and Shimon Sakaguchi and Masayuki Amagai},

doi = {10.1126/scitranslmed.adq9913},

issn = {1946-6242},

year  = {2025},

date = {2025-10-01},

journal = {Sci Transl Med},

volume = {17},

number = {821},

pages = {eadq9913},

abstract = {Antigen-specific immunotherapy represents one candidate strategy for treating autoimmune diseases such as pemphigus vulgaris, a skin autoimmune disorder mediated by anti-desmoglein 3 (Dsg3) autoantibodies. We developed a therapeutic strategy by which Dsg3-specific pathogenic autoreactive CD4 T cells were converted in vitro into functionally stable Foxp3 regulatory T (T) cells, designated stable and functional induced T (S/F-iT) cells. The conversion was achieved by pharmacological induction of Foxp3 and costimulation-dependent installation of T cell-specific epigenetic changes. In an animal model of pemphigus vulgaris, the Dsg3-specific S/F-iT cells expanded specifically in the skin-draining lymph nodes through recognition of endogenous Dsg3. They selectively inhibited Dsg3-specific T follicular helper cell and B cell proliferation and, consequently, anti-Dsg3 autoantibody formation, without affecting the total B cell population, thereby mitigating disease progression without inducing systemic immunosuppression. Human S/F-iT cells with similar functions could also be efficiently generated from peripheral blood T cells of patients with pemphigus vulgaris. This study demonstrates that pathogenic autoreactive T cells can be converted into disease-specific T cells retaining antigen specificity, enabling antigen- and disease-specific treatment of autoimmune disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41146073,

title = {Polyclonal immunoglobulin G deposits with distinctive appearance in the tubular basement membrane: a report of two cases},

author = {Yusuke Sakamaki and Akinori Hashiguchi and Konosuke Konishi and Takashi Araki and Hirobumi Tokuyama},

doi = {10.1186/s12882-025-04522-4},

issn = {1471-2369},

year  = {2025},

date = {2025-10-01},

journal = {BMC Nephrol},

volume = {26},

number = {1},

pages = {591},

abstract = {BACKGROUND: Tubulointerstitial diseases arise from various etiologies, including infections, medications, autoimmune conditions, and systemic disorders. The histological presentation of the tubulointerstitium in renal biopsies can vary considerably. When tubulointerstitial alterations are identified through light microscopy, additional evaluation with immunofluorescence and electron microscopy may assist in diagnosis. This report describes two slowly progressive atypical cases of tubulointerstitial disease. Renal biopsy in both cases revealed tubular atrophy and interstitial fibrosis with limited inflammatory cell infiltration, along with polyclonal linear immunoglobulin G (IgG) staining pattern along the thickened tubular basement membrane (TBM) and distinctive electron-dense deposits.nnCASE PRESENTATION: nnCASE 1:: A 65-year-old Japanese man with a history of chronic obstructive pulmonary disease, benign prostatic hyperplasia, and hypertension presented with anorexia and malaise 1 week prior to admission. Blood tests demonstrated marked renal impairment. Renal biopsy findings included relatively preserved glomeruli, widespread tubular atrophy, and significant interstitial fibrosis. Immunofluorescence showed linear deposition of IgG as well as kappa and lambda light chains along the TBM. Complement components C3 was also positive, and C1q were weakly positive. IgG subclass staining revealed positivity for IgG1, IgG2, and IgG4. Electron microscopy revealed electron-dense deposits within the TBM and on the epithelial side of the TBM, exhibiting a mottled and speckled appearance.nnCASE 2:: A 52-year-old Japanese man who had undergone allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia developed mild proteinuria and renal dysfunction 7 years after transplant. Renal biopsy indicated thrombotic microangiopathy, with glomeruli showing diffuse mesangial expansion and focal mesangiolysis. There was also diffuse TBM thickening and interstitial fibrosis with scattered cellular infiltration. Immunofluorescence demonstrated linear staining of polyclonal IgG and both light chains along the TBM. C3 was also positive while C1q was negative. IgG subclass staining revealed positivity for IgG1 and IgG4. Electron microscopy again identified electron-dense deposits within the reticulated TBM.nnCONCLUSIONS: These two cases demonstrated linear IgG immunofluorescence and distinctive electron-dense deposits in the TBM characterized by a mottled and speckled pattern. Although the underlying pathophysiological mechanisms remain unclear, further research is necessary to elucidate the nature of this form of tubulointerstitial disease.nnSUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-025-04522-4.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40643817,

title = {Tubulointerstitial nephritis with predominant monotypic plasma cell infiltration in three cases of Sjögren's syndrome: case reports and literature review},

author = {Hiroaki Miyauchi and Tatsuhiko Azegami and Akinori Hashiguchi and Mika Misaki and Takahisa Kawaguchi and Hironari Hanaoka and Mizuho Muramatsu and Takayoshi Soga and Takashi Ando and Eiji Kubota and Takashin Nakayama and Norifumi Yoshimoto and Akihito Hishikawa and Aika Hagiwara and Yuko Kaneko and Kaori Hayashi},

doi = {10.1007/s13730-025-01019-9},

issn = {2192-4449},

year  = {2025},

date = {2025-10-01},

journal = {CEN Case Rep},

volume = {14},

number = {5},

pages = {774--780},

abstract = {Tubulointerstitial nephritis (TIN) is a common kidney manifestation of Sjögren's syndrome, typically characterized by interstitial infiltration of T and B cells, with plasma cells being more prominent than in other etiologies. While most plasma cell infiltration in TIN is polytypic and the importance of the immunoglobulin isotypes expressed by the infiltrating plasma cells in the pathogenesis is unknown, recent reports have identified rare cases with monotypic IgA-positive plasma cell infiltration accompanied by monoclonal gammopathy of undetermined significance (MGUS). Here, we present three cases of Sjögren syndrome-associated TIN characterized by monotypic plasma cell infiltration. In all cases, the isotype of the infiltrating plasma cells was consistent with that of the predominant serum immunoglobulin. One patient exhibited IgA-type MGUS, one had IgM-type MGUS, and one showed elevated serum IgG levels along with IgG-positive plasma cell infiltration, but without detectable paraproteinemia. Notably, serum immunoglobulin levels decreased in parallel with improvement in kidney function. These findings suggest a potential link between the systemic immunoglobulin profile and local immunopathology of the kidneys in Sjögren's syndrome. Further case accumulation is needed to clarify the clinical significance and pathophysiology of monotypic plasma cell infiltration in TIN associated with Sjögren's syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40489000,

title = {Phenotype-dependent heterogeneity of THSD7A expression in gastric cancer tissue in a patient with THSD7A-associated membranous nephropathy},

author = {Chisato Minezaki and Tatsuhiko Azegami and Akinori Hashiguchi and Takashin Nakayama and Norifumi Yoshimoto and Akihito Hishikawa and Aika Hagiwara and Kaori Hayashi},

doi = {10.1007/s13730-025-01006-0},

issn = {2192-4449},

year  = {2025},

date = {2025-10-01},

journal = {CEN Case Rep},

volume = {14},

number = {5},

pages = {693--699},

abstract = {An 88-year-old Japanese man with benign prostatic hyperplasia was presented to our hospital because of proteinuria and generalized edema. He was diagnosed with nephrotic syndrome and underwent a kidney biopsy, which revealed thickening of the capillary wall, spike formation, and subepithelial deposits, leading to histopathological diagnosis of membranous nephropathy. IgG4-dominant deposits were observed in IgG subclass staining, and immunostaining for thrombospondin type 1 domain-containing 7A (THSD7A) demonstrated granular staining along the capillary wall. A malignancy screening was performed, which led to the detection of gastric cancer. Malignancy-associated membranous nephropathy secondary to gastric cancer was suspected, and priority was given to the treatment of gastric cancer. Three months after undergoing radical surgery for gastric cancer, his nephrotic syndrome achieved remission. The histopathological diagnosis of gastric cancer was papillary adenocarcinoma. In the surgical specimen of the gastric cancer, THSD7A was positive in the tumor cells with intestinal phenotype and negative in gastric foveolar phenotype. These findings suggest that the acquisition of the ability to express THSD7A by cancer transformation in multi-step carcinogenesis of gastric cancer may be involved in the development of malignancy-associated membranous nephropathy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40314902,

title = {Blood Group Antigen Expression in Blood and Tumor in Relation to Survival Outcomes in Resected Pancreatic Cancer, Overall and by Adjuvant Chemotherapy Regimens},

author = {Yosuke Inoue and Manabu Takamatsu and Yohei Masugi and Tatsunori Suzuki and Tsuyoshi Hamada and Satoru Abe and Kensuke Hara and Yoshikuni Kawaguchi and Kosuke Kobayashi and Aya Maekawa and Yousuke Nakai and Naoki Sasahira and Tsuyoshi Takeda and Mariko Tanaka and Yosuke Uematsu and Sho Uemura and Tetsuo Ushiku and Mitsuhiro Fujishiro and Kengo Takeuchi and Minoru Kitago and Kiyoshi Hasegawa and Yu Takahashi and },

doi = {10.1245/s10434-025-17289-7},

issn = {1534-4681},

year  = {2025},

date = {2025-09-01},

journal = {Ann Surg Oncol},

volume = {32},

number = {9},

pages = {6477--6491},

abstract = {BACKGROUND: Few comprehensive studies have examined the associations of the ABO blood group with survival outcomes for patients with resected pancreatic cancer, overall and by adjuvant chemotherapy regimens.nnMETHODS: This multicenter study enrolled 1153 patients with resected pancreatic cancer. The hazard ratios (HRs) for disease-free and pancreatic cancer-specific survival were calculated with adjustment for potential confounders, including KRAS mutation and CDKN2A (p16), TP53, and SMAD4 expression, using the Cox proportional hazards regression model. Blood group antigen expression in tumors was immunohistochemically assessed.nnRESULTS: The ABO blood group was not associated with disease-free or pancreatic cancer-specific survival (P > 0.90). For pancreatic cancer-specific survival, blood groups A, B, and AB had multivariable HRs of 0.97 (95% confidence interval [CI], 0.81-1.15), 1.03 (95% CI, 0.83-1.26), and 0.99 (95% CI, 0.76-1.30), respectively (vs. O). The associations between ABO blood group and disease-free and pancreatic cancer-specific survival differed according to the adjuvant chemotherapy regimens (P = 0.011 and 0.008, respectively). For the patients without chemotherapy, the HRs for disease-free survival were 0.99 (95% CI, 0.69-1.41) for blood group A, 1.65 (95% CI, 1.09-2.48) for blood group B, and 1.79 (95% CI, 1.01-3.17) for blood group AB, (vs. O). For the patients receiving S-1-based chemotherapy, blood group AB (vs. O) exhibited a reverse association (HR, 0.63; 95% CI, 0.39-1.00). Similar interactions were observed when blood group antigen expression in tumors was analyzed.nnCONCLUSIONS: The ABO blood group is not a prognostic biomarker in resected pancreatic cancer overall but may predict the effectiveness of adjuvant chemotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40338425,

title = {Distribution of Lymph Node Metastasis and Prognosis in Duodenal Bulb Tumors: A Multicenter Retrospective Study},

author = {Kazuhiko Hisaoka and Satoru Matsuda and Hirofumi Kawakubo and Masashi Takeuchi and Takeyuki Wada and Shigeki Sekine and Takeshi Takamoto and Mai Tsutsui and Masahiro Yura and Hiroki Ishida and Yoshihiro Ono and Satoshi Kamiya and Etsuro Bando and Soya Nunobe and Takahiro Kinoshita and Yuko Kitagawa},

doi = {10.1245/s10434-025-17388-5},

issn = {1534-4681},

year  = {2025},

date = {2025-09-01},

journal = {Ann Surg Oncol},

volume = {32},

number = {9},

pages = {6492--6500},

abstract = {BACKGROUND: The optimal surgical procedure for primary duodenal cancer has not been established because of its low incidence. The purpose of this study was to examine the distribution of lymph node (LN) metastasis in duodenal bulb tumors. Specifically, in tumors with submucosal invasion, we aimed to evaluate the feasibility of distal gastrectomy with duodenal bulb resection combined with lymphadenectomy of regional gastric LNs.nnMETHODS: Data from patients who underwent surgery for either adenocarcinoma or neuroendocrine tumors located in the duodenal bulb between 2000 and 2020 were retrospectively analyzed from five high-volume centers in Japan. Patient background, clinicopathological factors, type of surgery, distribution of LN metastasis, and long-term outcomes were evaluated.nnRESULTS: The frequency of LN metastasis in tumors with submucosal invasion was 18%. Metastatic LNs were identified in T1b adenocarcinomas for #6, #8a, #8p, with similar results for neuroendocrine tumors. The 3-year overall survival rate for adenocarcinoma in stages T1a, T1b, and T2-4 was 100%, 81%, and 56%, respectively. Neuroendocrine tumors were 100% at all depths of invasion. Regarding LN tumors with submucosal invasion, while three patients had a recurrence, two cases were observed in distant organs without regional LNs, and one patient who underwent pancreaticoduodenectomy had metastasis in the gastric regional LNs.nnCONCLUSION: For duodenal bulb tumors, based on the distribution of LN metastasis with tumors with submucosal invasion, distal gastrectomy with duodenal bulb resection and regional LN dissection is considered a curative treatment. Conversely, pancreaticoduodenectomy is recommended for tumors invading the muscularis propria and beyond.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40739358,

title = {ACLY inhibition promotes tumour immunity and suppresses liver cancer},

author = {Jaya Gautam and Jianhan Wu and James S V Lally and Jamie D McNicol and Russta Fayyazi and Elham Ahmadi and Daniela Carmen Oniciu and Spencer Heaton and Roger S Newton and Sonia Rehal and Dipankar Bhattacharya and Fiorella Di Pastena and Binh Nguyen and Celina M Valvano and Logan K Townsend and Suhrid Banskota and Battsetseg Batchuluun and Maria Joy Therese Jabile and Alice Payne and Junfeng Lu and Eric M Desjardins and Naoto Kubota and Evangelia E Tsakiridis and Bejal Mistry and Alex Aganostopoulos and Vanessa Houde and Ann Dansercoer and Koen H G Verschueren and Savvas N Savvides and Joanne A Hammill and Ksenia Bezverbnaya and Paola Muti and Theodoros Tsakiridis and Wenting Dai and Lei Jiang and Yujin Hoshida and Mark Larché and Jonathan L Bramson and Scott L Friedman and Kenneth Verstraete and Dongdong Wang and Gregory R Steinberg},

doi = {10.1038/s41586-025-09297-0},

issn = {1476-4687},

year  = {2025},

date = {2025-09-01},

journal = {Nature},

volume = {645},

number = {8080},

pages = {507--517},

abstract = {Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC). Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation. Although ACLY inhibition shows antiproliferative effects in various tumours, clinical translation has been limited by challenges in inhibitor development and compensatory metabolic pathways. Here, using a mouse model of MASH-HCC that mirrors human disease, genetic inhibition of ACLY in hepatocytes and tumours reduced neoplastic lesions by over 70%. To evaluate the therapeutic potential of this pathway, a novel small-molecule ACLY inhibitor, EVT0185 (6-[4-(5-carboxy-5-methyl-hexyl)-phenyl]-2,2-dimethylhexanoic acid), was identified via phenotypic screening. EVT0185 is converted to a CoA thioester in the liver by SLC27A2 and structural analysis by cryo-electron microscopy reveals that EVT0185-CoA directly interacts with the CoA-binding site of ACLY. Oral delivery of EVT0185 in three mouse models of MASH-HCC dramatically reduces tumour burden as monotherapy and enhances efficacy of current standards of care including tyrosine kinase inhibitors and immunotherapies. Transcriptomic and spatial profiling in mice and humans linked reduced tumour ACLY with increases in the chemokine CXCL13, tumour-infiltrating B cells and tertiary lymphoid structures. The depletion of B cells blocked the antitumour effects of ACLY inhibition. Together, these findings illustrate how targeting tumour metabolism can rewire immune function and suppress cancer progression in MASH-HCC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40866351,

title = {Clonal diversity shapes the tumour microenvironment leading to distinct immunotherapy responses in metastatic urothelial carcinoma},

author = {Takashi Kamatani and Kota Umeda and Tomohiro Iwasawa and Fuyuki Miya and Kazuhiro Matsumoto and Shuji Mikami and Kensuke Hara and Masayuki Shimoda and Yutaka Suzuki and Jo Nishino and Mamoru Kato and Kazuhiro Kakimi and Nobuyuki Tanaka and Mototsugu Oya and Tatsuhiko Tsunoda},

doi = {10.1038/s41467-025-63309-1},

issn = {2041-1723},

year  = {2025},

date = {2025-08-01},

journal = {Nat Commun},

volume = {16},

number = {1},

pages = {7995},

abstract = {Repeated oncogenic mutations and polyclonal proliferation are evident in cancers. However, little is known about the polyclonal principles governing the systemic cancerous lineage during immunotherapy. Here, we examine a unique autopsy case of metastatic urothelial carcinoma that exhibits different treatment responses to anti-PD-1 therapy at each tumor site. By performing in-depth analyses of different multiregional bulk tumor masses, we reveal that subsets of subclones acquire potential driver mutations under treatment selection pressure. Spatial transcriptomics analysis reveals that subclones resistant to immunotherapy form distinct immunosuppressive environments consistent with their habitats. Furthermore, different cancer hallmarks are identified in each of the subclones that expand under immunotherapy at single-cell level; for example, one subclone is more proliferative, and another is more stem-cell-like. In summary, this study provides an overall picture of the polyclonal competition and changes in the immune microenvironment that are related to resistance to immunotherapy in patients with malignancies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40447912,

title = {A case of IgA nephropathy associated with Crohn's disease treated with enteric-coated budesonide},

author = {Ryuto Yoshida and Takashin Nakayama and Akinori Hashiguchi and Tatsuhiko Azegami and Kaori Hayashi},

doi = {10.1007/s13730-025-01001-5},

issn = {2192-4449},

year  = {2025},

date = {2025-08-01},

journal = {CEN Case Rep},

volume = {14},

number = {4},

pages = {659--664},

abstract = {The gut-kidney axis has recently gained attention as a pathogenesis of IgA nephropathy (IgAN). In fact, the efficacy of target-release formulation of budesonide for IgAN has been reported in recent studies. On the other hand, there have been no reports yet on the efficacy of enteric-coated budesonide for IgAN complicated with inflammatory bowel disease. We report a case of IgAN with comorbid Crohn's disease (CD) treated with a combination of enteric-coated budesonide and methylprednisolone pulse therapy. The patient was followed for 2 years. He showed initial reduction in proteinuria following treatment. However, after discontinuation of enteric-coated budesonide therapy, proteinuria recurred despite well-controlled CD. Enteric-coated budesonide combined with methylprednisolone pulse therapy may be effective in short-term reduction of proteinuria while minimizing systemic steroid side effects in IgAN associated with CD. However, the tendency for relapse suggests the need for long-term management strategies. Therefore, further research is needed to establish optimal treatment protocols for this patient population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40221577,

title = {An adolescent presenting with IgA nephropathy and persistent decreased kidney function after COVID-19 vaccination during follow-up for asymptomatic hematuria: a clinicopathological study},

author = {Kazumi Morisawa and Tsutomu Takahashi and Kentaro Matsuoka and Akinori Hashiguchi and Mariko Yamanaka and Riku Hamada and Masataka Honda},

doi = {10.1007/s13730-025-00989-0},

issn = {2192-4449},

year  = {2025},

date = {2025-08-01},

journal = {CEN Case Rep},

volume = {14},

number = {4},

pages = {635--640},

abstract = {Although the coronavirus disease 2019 (COVID-19) vaccine has been proven to be effective and safe in most adults and children, various diseases, including IgA nephropathy, sometimes occur as an adverse effect. We herein describe a case of IgA nephropathy in a 16-year-old, male patient with persistent kidney dysfunction following COVID-19 vaccination and present the clinicopathological course of the disease. The patient presented to the outpatient clinic with a history of gross hematuria 6 days after receiving the COVID-19 vaccine. Prior to the current presentation, he was being examined regularly at an outpatient clinic for asymptomatic hematuria. His mother had received a diagnosis of IgA nephropathy, and his younger brother had received a diagnosis of asymptomatic hematuria. A blood test of this patient demonstrated elevated serum creatinine, and IgA nephropathy was pathologically diagnosed (Oxford classification M0E1S1T0C1). Prednisolone and immunosuppressants were administered promptly to treat the decreased kidney function and the pathology. Nevertheless, the failure of his kidney function to recover to the state it was in prior to this episode may have led to the formation of chronic lesions, causing irreversible kidney tissue damage. Some patients with IgA nephropathy, asymptomatic hematuria or a family history of kidney-related symptoms may experience kidney dysfunction after COVID-19 vaccination and require prednisolone or immunosuppressive therapy to stem the progressive deterioration of their kidney function. Prior to receiving the COVID-19 vaccine, patients with any of these conditions should be provided with an appropriate explanation of the risks and be asked for their consent to be vaccinated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40065709,

title = {Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway},

author = {Tomoko Aoki and Naoshi Nishida and Yutaka Kurebayashi and Kazuko Sakai and Naoto Fujiwara and Masakatsu Tsurusaki and Kohei Hanaoka and Masahiro Morita and Hirokazu Chishina and Masahiro Takita and Satoru Hagiwara and Hiroshi Ida and Kazuomi Ueshima and Yasunori Minami and Atsushi Takebe and Takaaki Murase and Keiko Kamei and Takuya Nakai and Ippei Matsumoto and Kazuto Nishio and Masatoshi Kudo},

doi = {10.3350/cmh.2024.1088},

issn = {2287-285X},

year  = {2025},

date = {2025-07-01},

journal = {Clin Mol Hepatol},

volume = {31},

number = {3},

pages = {981--1002},

abstract = {BACKGROUND/AIMS: Previously, we advocated the importance of classifying hepatocellular carcinoma (HCC) based on physiological functions. This study aims to classify HCC by focusing on liver-intrinsic metabolism and glycolytic pathway in cancer cells.nnMETHODS: Comprehensive RNA/DNA sequencing, immunohistochemistry, and radiological evaluations were performed on HCC tissues from the training cohort (n=136) and validated in 916 public samples. HCC was classified using hierarchical clustering and compared with previous molecular, histopathological, and hemodynamic classifications.nnRESULTS: Liver-specific metabolism and glycolysis are mutually exclusive and were divided into two major subclasses: The "rich metabolism" subclass (60.3%) is characterized by enhanced bile acid and fatty acid metabolism, wellto-moderate differentiation, microtrabecular or pseudoglandular pattern, and homogeneous arterial-phase hyperenhancement (APHE), corresponding to Hoshida S3 with favorable prognosis. In IL6-JAK-STAT3-high (25.0%) conditions, upregulated ALB expression, enhanced gluconeogenesis and urea cycle activity, and an inflammatorymicroenvironment are observed. Conversely, the Wnt/β-catenin-high environment (19.9%) features elevated GLUL, APOB and CYP3A4 expression, frequent CTNNB1 (D32-S37) mutations, and an immune-desert/excluded phenotype. The "glycolysis" subclass (39.7%), characterized by histopathological dedifferentiation and downregulated liver-specific metabolism, encompasses subclasses with PI3K/mTOR (20.6%) and NOTCH/TGF-β (19.1%) signaling. These often exhibit TP53 mutations, macrotrabecular massive or compact patterns, inhomogeneous/rim-APHE, and high expression of hypoxia-inducible factors and glucose transporters, corresponding to Hoshida S1/2 with poor prognosis.nnCONCLUSION: The loss of liver-specific metabolism correlates with morphological dedifferentiation, indicating cellular dedifferentiation may exhibit both physiological and pathological duality. Key signaling pathways involved in the maturation process from fetal to adult liver and zonation program may play a critical role in defining HCC diversity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40243533,

title = {Density of T-cell Subsets in Colorectal Cancer in Relation to Disease-Specific Survival},

author = {Claire E Thomas and Yasutoshi Takashima and Daniel D Buchanan and Evertine Wesselink and Conghui Qu and Li Hsu and Andressa Dias Costa and Steven Gallinger and Robert C Grant and Jeroen R Huyghe and Sushma Thomas and Satoko Ugai and Yuxue Zhong and Kosuke Matsuda and Tomotaka Ugai and Ulrike Peters and Shuji Ogino and Jonathan A Nowak and Amanda I Phipps},

doi = {10.1158/1055-9965.EPI-25-0287},

issn = {1538-7755},

year  = {2025},

date = {2025-07-01},

journal = {Cancer Epidemiol Biomarkers Prev},

volume = {34},

number = {7},

pages = {1122--1133},

abstract = {BACKGROUND: Prior studies have demonstrated that the overall density of T cells in colorectal tumors is favorably associated with colorectal cancer survival; however, few studies have considered the potentially distinct roles of heterogeneous T-cell subsets in different tissue regions in relation to colorectal cancer outcomes.nnMETHODS: Including 1,113 colorectal cancer tumors from three observational studies, we conducted in situ T-cell profiling using a customized nine-plex [CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT (keratin), MKI67 (Ki-67), and DAPI] multispectral immunofluorescence assay. Multivariable-adjusted Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the associations of T-cell subset densities in both epithelial and stromal tissue areas in colorectal cancer with disease-specific survival.nnRESULTS: Higher CD3+CD4+ and CD3+CD8+ naïve, memory, and regulatory T-cell densities were significantly associated with better colorectal cancer-specific survival in both epithelial and stromal tissue areas (HR highest quantile vs. lowest quantile ranging 0.41-0.68). These associations persisted in models further adjusted for stage at diagnosis and were largely consistent when stratified by microsatellite instability status. However, the further stratification into CD4+ or CD8+ T-cell subsets beyond CD3+ subsets did not significantly improve the performance of our model in explaining colorectal cancer prognosis.nnCONCLUSIONS: The density of T cells in colorectal cancer tissue, both overall and for several T-cell subset populations, is significantly associated with colorectal cancer-specific survival independent of microsatellite instability status and stage at diagnosis.nnIMPACT: Higher levels of T-cell densities in different locations with different functions are associated with better colorectal cancer-specific survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39721684,

title = {Membranous Nephropathy Associated with Syphilis: Correlative Light and Electron Microscopy Revealing the Localization of Neuron-derived Neurotrophic Factor within Subepithelial Electron Dense Deposits},

author = {Chisato Minezaki and Tatsuhiko Azegami and Akinori Hashiguchi and Ayumi Yoshifuji and Norifumi Yoshimoto and Aika Hagiwara and Akihito Hishikawa and Kaori Hayashi},

doi = {10.2169/internalmedicine.4699-24},

issn = {1349-7235},

year  = {2025},

date = {2025-07-01},

journal = {Intern Med},

volume = {64},

number = {14},

pages = {2202--2207},

abstract = {A 50-year-old man presented to our hospital with a fever, edema, and a rash. The clinical diagnosis was renal dysfunction, nephrotic syndrome, and syphilis. The patient was treated with benzylpenicillin, and his symptoms improved. A renal biopsy revealed membranous nephropathy (MN). Recently, neuron-derived neurotrophic factor (NDNF) was reported to be an antigen corresponding to syphilis-associated MN. In the present patient, immunofluorescence staining and immunoelectron microscopy revealed granular NDNF-positive findings within subepithelial deposits, suggesting the presence of NDNF-IgG immune complexes. Although the mechanism by which NDNF serves as a target antigen remains unclear, NDNF was found to colocalize within subepithelial immune complexes in syphilis-associated MN.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39844451,

title = {Spectrum of gastric neoplasms in Helicobacter pylori-naïve patients},

author = {Kotaro Shibagaki and Ryoji Kushima and Shigeki Sekine and Tsuyoshi Mishiro and Satoshi Kotani and Yoichi Miyaoka and Norihisa Ishimura and Asuka Araki and Hideyuki Ohnuma and Daisuke Niino and Shunji Ishihara},

doi = {10.1111/den.14980},

issn = {1443-1661},

year  = {2025},

date = {2025-06-01},

journal = {Dig Endosc},

volume = {37},

number = {6},

pages = {611--628},

abstract = {Chronic Helicobacter pylori (Hp) infection is the largest etiological factor for gastric cancer, but in recent years the reports of Hp-naïve gastric neoplasms (HpNGNs) have increased as the Hp-infected population in Japan has been declining. The histopathologic spectrum of HpNGNs differs significantly from that of conventional Hp-infected gastric neoplasms. Molecularly, the former harbor considerably fewer genetic and epigenetic abnormalities, reflecting the absence of chronic inflammatory conditions in the gastric mucosa. The majority of HpNGNs fall within several specific histological entities; each arise from particular background mucosa. Most originate from the fundic gland mucosa and have a gastric immunophenotype, as seen in foveolar-type gastric adenoma (FGA), oxyntic gland adenoma (OGA)/gastric adenocarcinoma of fundic gland type (GA-FG), signet-ring cell carcinoma (SRCC), and sporadic fundic gland polyp with dysplasia (FGPD). In contrast, tumors arising from the pyloric or cardiac gland mucosa have a diverse immunophenotype, as seen in intestinal-type gastric dysplasia (IGD) and gastric cardiac carcinoma. FGA, FGPD, SRCC, and IGD are mostly found as small intramucosal lesions. OGA/GA-FG frequently progresses to invasive carcinoma, but only a few have lymph node metastases. Thus, these tumors are regarded as precancerous lesions by Western pathologists, while in Japan they tend to be diagnosed as carcinomas, even in cases of low-grade dysplasia. Gastric cardiac carcinomas, on the other hand, are often found as advanced carcinomas and harbor a high malignant biological potential. A new diagnostic framework for gastric neoplasms is required in the present era of Hp-naïve individuals in Japan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40237914,

title = {Taurine supplementation improves physical activity level in a hemodialysis patient with mitochondrial disease: a case report},

author = {Ryuto Yoshida and Ryunosuke Mitsuno and Takashin Nakayama and Tatsuhiko Azegami and Akinori Hashiguchi and Takuto Torimitsu and Norifumi Yoshimoto and Akihito Hisikawa and Aika Hagiwara and Toshifumi Nakamura and Shu Meguro and Masahiro Katsumata and Jin Endo and Tatsuo Matsunaga and Jun Yoshino and Takeshi Kanda and Kohkichi Morimoto and Toshiaki Monkawa and Tadashi Yoshida and Jin Nakahara and Shintaro Yamaguchi and Kaori Hayashi},

doi = {10.1007/s13730-025-00992-5},

issn = {2192-4449},

year  = {2025},

date = {2025-06-01},

journal = {CEN Case Rep},

volume = {14},

number = {3},

pages = {366--373},

abstract = {Mitochondrial diseases (MDs) are inherited metabolic disorders that affect multiple organ systems, including the kidneys. Variability in disease onset and phenotypic expression, combined with the absence of specific kidney pathological findings, pose significant challenges in diagnosing MD. Consequently, many undiagnosed cases of MD may exist among patients undergoing dialysis. No effective treatment for mitochondrial nephropathy has been established. We report the case of a 27-year-old female patient who presented with leg edema, nephrotic range proteinuria attributed to focal segmental glomerulosclerosis, and bilateral sensorineural hearing loss. Immunosuppressive therapy failed to achieve remission, resulting in progressive kidney function decline and eventual end-stage kidney disease. At hemodialysis initiation, worsening atypical cardiac function and hypertrophy prompted genetic testing, which identified an MT-TL1 m.3243 A > G mutation and confirmed the diagnosis of MD. After hemodialysis initiation, the patient experienced persistent fatigue and decreased physical activity levels despite dry weight management. Suspected stroke-like symptoms prompted the initiation of taurine supplementation, which significantly improved headache severity, cardiac function, and physical activity levels. This case highlights the therapeutic potential of taurine supplementation in patients with MD undergoing dialysis and the importance of maintaining clinical vigilance for MD across all stages of chronic kidney disease, even without characteristic renal pathological findings of mitochondrial nephropathy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40350470,

title = {Basal-shift transformation leads to EGFR therapy-resistance in human lung adenocarcinoma},

author = {Taro Shinozaki and Kazuhiro Togasaki and Junko Hamamoto and Akifumi Mitsuishi and Takahiro Fukushima and Kai Sugihara and Toshiki Ebisudani and Masahiko Okada and Ayaka Saito and Lisa Shigematsu and Hatsuyo Takaoka and Fumimaro Ito and Keiko Ohgino and Kota Ishioka and Kageaki Watanabe and Tsunekazu Hishima and Yutaka Kurebayashi and Katsura Emoto and Hideki Terai and Shinnosuke Ikemura and Ichiro Kawada and Keisuke Asakura and Tomoyuki Hishida and Hisao Asamura and Yuki Ohta and Sirirat Takahashi and Mayumi Oda and Megumu Saito and Mami Matano and Kenzo Soejima and Masayuki Fujii and Koichi Fukunaga and Hiroyuki Yasuda and Toshiro Sato},

doi = {10.1038/s41467-025-59623-3},

issn = {2041-1723},

year  = {2025},

date = {2025-05-01},

journal = {Nat Commun},

volume = {16},

number = {1},

pages = {4369},

abstract = {Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) are effective for EGFR-mutant lung adenocarcinoma (LUAD), resistance inevitably develops through diverse mechanisms, including secondary genetic mutations, amplifications and as-yet undefined processes. To comprehensively unravel the mechanisms of EGFR-TKI resistance, we establish a biobank of patient-derived EGFR-mutant lung cancer organoids, encompassing cases previously treated with EGFR-TKIs. Through comprehensive molecular profiling including single-cell analysis, here we identify a subgroup of EGFR-TKI-resistant LUAD organoids that lacks known resistance-related genetic lesions and instead exhibits a basal-shift phenotype characterized by the hybrid expression of LUAD- and squamous cell carcinoma-related genes. Prospective gene engineering demonstrates that NKX2-1 knockout induces the basal-shift transformation along with EGFR-target therapy resistance. Basal-shift LUADs frequently harbor CDKN2A/B loss and are sensitive to CDK4/6 inhibitors. Our EGFR-mutant lung cancer organoid library not only offers a valuable resource for lung cancer research but also provides insights into molecular underpinnings of EGFR-TKI resistance, facilitating the development of therapeutic strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40307487,

title = {An organoid library unveils subtype-specific IGF-1 dependency via a YAP-AP1 axis in human small cell lung cancer},

author = {Takahiro Fukushima and Kazuhiro Togasaki and Junko Hamamoto and Katsura Emoto and Toshiki Ebisudani and Akifumi Mitsuishi and Kai Sugihara and Taro Shinozaki and Masahiko Okada and Ayaka Saito and Hatsuyo Takaoka and Fumimaro Ito and Lisa Shigematsu and Yuki Ohta and Sirirat Takahashi and Mami Matano and Yutaka Kurebayashi and Keiko Ohgino and Takashi Sato and Ichiro Kawada and Keisuke Asakura and Tomoyuki Hishida and Hisao Asamura and Shinnosuke Ikemura and Hideki Terai and Kenzo Soejima and Mayumi Oda and Masayuki Fujii and Koichi Fukunaga and Hiroyuki Yasuda and Toshiro Sato},

doi = {10.1038/s43018-025-00945-y},

issn = {2662-1347},

year  = {2025},

date = {2025-05-01},

journal = {Nat Cancer},

volume = {6},

number = {5},

pages = {874--891},

abstract = {Small cell lung cancer (SCLC) is a devastating disease with limited therapeutic advancements. Although SCLC has recently been classified into four molecular subtypes, subtype-specific therapies are still lacking. Here, we established 40 patient-derived SCLC organoid lines with predominant TP53 and RB1 alterations and rare targetable genetic lesions. Transcriptome profiling divided the SCLC organoids into neuroendocrine (NE)-type SCLC and non-NE-type SCLC, with the latter characterized by YAP1 or POU2F3 expression. NE-type SCLC organoids grew independent of alveolar niche factors, whereas non-NE-type SCLC organoids relied on insulin-like growth factor (IGF)-1-driven YAP1 and AP1 activation. Therapeutic targeting of IGF-1, YAP1 and AP1 effectively suppressed the growth of non-NE-type organoids. Co-knockout of TP53 and RB1 in human alveolar cells altered their lineage toward the airway epithelium-like fate and conferred IGF-1 dependency, validating the subtype-phenotype connection. Our SCLC organoid library represents a valuable resource for developing biology-based therapies and has the potential to reshape the drug discovery landscape.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39566540,

title = {Procedural outcomes of a novel underwater injection endoscopic mucosal resection technique for colorectal polyps ≥10 mm},

author = {Yuichiro Hirai and Naoya Toyoshima and Hiroyuki Takamaru and Masau Sekiguchi and Masayoshi Yamada and Nozomu Kobayashi and Shigeki Sekine and Yutaka Saito},

doi = {10.1055/a-2479-9227},

issn = {1438-8812},

year  = {2025},

date = {2025-05-01},

journal = {Endoscopy},

volume = {57},

number = {5},

pages = {494--499},

abstract = {It is uncertain whether underwater endoscopic mucosal resection (UEMR) enables resection of the submucosal tissue with sufficient margins for T1 colorectal cancer (CRC) because UEMR forgoes submucosal injection. Therefore, we developed a novel "underwater injection EMR" (UIEMR) method that combines submucosal injection with UEMR to obtain an adequate vertical margin.We retrospectively analyzed procedure-related outcomes of 135 consecutive lesions from patients who underwent UIEMR for ≥10-mm nonpedunculated colorectal polyps (median size 15 mm). The outcomes included the en bloc, R0, RX, and R1 resection rates, and adverse events. Additionally, the vertical margin distance of seven T1 CRCs was evaluated.En bloc resection was achieved in 127 lesions (94.1%). R0 and RX resections were observed in 92 (68.1%) and 42 lesions (31.1%), respectively, while R1 resection was seen in only one lesion (0.7%). There were two cases with adverse events (1.5%), both delayed bleeding. In T1 CRCs, all seven cases had free vertical margins, and the median vertical margin distance was 1140 µm (range 731-1570 µm).UIEMR safely demonstrated high success rates for en bloc resection, and potentially ensures a sufficient vertical margin. This technique might be an option, particularly for relatively small lesions concerning for T1 CRC, and deserves further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39775861,

title = {Chronological changes in etiology, pathological and imaging findings in primary liver cancer from 2001 to 2020},

author = {Junya Tsuzaki and Akihisa Ueno and Yohei Masugi and Masashi Tamura and Seiichiro Yamazaki and Kosuke Matsuda and Yutaka Kurebayashi and Hiroto Sakai and Yoichi Yokoyama and Yuta Abe and Koki Hayashi and Yasushi Hasegawa and Hiroshi Yagi and Minoru Kitago and Masahiro Jinzaki and Michiie Sakamoto},

doi = {10.1093/jjco/hyae187},

issn = {1465-3621},

year  = {2025},

date = {2025-04-01},

journal = {Jpn J Clin Oncol},

volume = {55},

number = {4},

pages = {362--371},

abstract = {PURPOSE: To achieve a historical perspective, the chronological changes in primary liver cancer over a 20-year period were investigated at a single institution, focusing on shifts in etiology and the impact on imaging and pathological findings using The Liver Imaging Reporting and Data System.nnMATERIALS AND METHODS: A retrospective study of surgically resected primary liver cancer in 680 patients from 2001 to 2020 resulted in 434 patients with 482 nodules being analyzed. Dynamic contrast-enhanced computed tomography imaging and the Liver Imaging Reporting and Data System 2018 classification were employed. Two pathologists and two radiologists independently evaluated specimens and images.nnRESULTS: This study highlighted a significant decline in cases of viral hepatitis and cirrhosis in primary liver cancer patients but an increase in intrahepatic cholangiocarcinoma and scirrhous hepatocellular carcinoma. Notably, there was a rise in non-viral hepatitis cases, potentially pointing toward an increase in steatohepatitic hepatocellular carcinoma cases in the future. Intrahepatic cholangiocarcinoma, scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma tumors exhibited slightly different distributions in the Liver Imaging Reporting and Data System classification compared with ordinary hepatocellular carcinoma, which may reflect the presence of fibrosis and lipid in tumor parenchyma.nnCONCLUSIONS: Consistent with past reports, this study demonstrated the emergence of primary liver cancer against a backdrop of non-viral and non-cirrhotic liver. Liver Imaging Reporting and Data System has been consistently useful in diagnosing primary liver cancer; however, among the histological subtypes of hepatocellular carcinoma, an increase is anticipated in scirrhous hepatocellular carcinoma and steatohepatitic hepatocellular carcinoma, which may present imaging findings different from those of ordinary hepatocellular carcinoma. This development may necessitate a reevaluation of the current approach for diagnosing and treating hepatocellular carcinoma based solely on imaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40295524,

title = {DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages},

author = {Erina Sugita Nishimura and Akihito Hishikawa and Ran Nakamichi and Riki Akashio and Shunsuke Chikuma and Akinori Hashiguchi and Norifumi Yoshimoto and Eriko Yoshida Hama and Tomomi Maruki and Wataru Itoh and Shintaro Yamaguchi and Jun Yoshino and Hiroshi Itoh and Kaori Hayashi},

doi = {10.1038/s41467-025-59297-x},

issn = {2041-1723},

year  = {2025},

date = {2025-04-01},

journal = {Nat Commun},

volume = {16},

number = {1},

pages = {3958},

abstract = {DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis reveals expansion of CD11c+ Ccr2+ macrophages in the kidney cortex, liver, and adipose tissues and Ly6C monocytes in peripheral blood. DNA damage in PTECs is associated with hypomethylation of macrophage activation genes, including Gasdermin D, in peripheral blood cells, which is linked to reduced DNA methylation at KLF9-binding motifs. Macrophage depletion ameliorates metabolic abnormalities. These findings highlight the impact of kidney DNA damage on systemic metabolic homeostasis, revealing a kidney-blood-metabolism axis mediated by epigenetic changes in macrophages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37300379,

title = {Molecular and immune landscape of hepatocellular carcinoma to guide therapeutic decision-making},

author = {Renumathy Dhanasekaran and Hiroyuki Suzuki and Lea Lemaitre and Naoto Kubota and Yujin Hoshida},

doi = {10.1097/HEP.0000000000000513},

issn = {1527-3350},

year  = {2025},

date = {2025-03-01},

journal = {Hepatology},

volume = {81},

number = {3},

pages = {1038--1057},

abstract = {Liver cancer, primarily HCC, exhibits highly heterogeneous histological and molecular aberrations across tumors and within individual tumor nodules. Such intertumor and intratumor heterogeneities may lead to diversity in the natural history of disease progression and various clinical disparities across the patients. Recently developed multimodality, single-cell, and spatial omics profiling technologies have enabled interrogation of the intertumor/intratumor heterogeneity in the cancer cells and the tumor immune microenvironment. These features may influence the natural history and efficacy of emerging therapies targeting novel molecular and immune pathways, some of which had been deemed undruggable. Thus, comprehensive characterization of the heterogeneities at various levels may facilitate the discovery of biomarkers that enable personalized and rational treatment decisions, and optimize treatment efficacy while minimizing the risk of adverse effects. Such companion biomarkers will also refine HCC treatment algorithms across disease stages for cost-effective patient management by optimizing the allocation of limited medical resources. Despite this promise, the complexity of the intertumor/intratumor heterogeneity and ever-expanding inventory of therapeutic agents and regimens have made clinical evaluation and translation of biomarkers increasingly challenging. To address this issue, novel clinical trial designs have been proposed and incorporated into recent studies. In this review, we discuss the latest findings in the molecular and immune landscape of HCC for their potential and utility as biomarkers, the framework of evaluation and clinical application of predictive/prognostic biomarkers, and ongoing biomarker-guided therapeutic clinical trials. These new developments may revolutionize patient care and substantially impact the still dismal HCC mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39521255,

title = {Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis},

author = {Naoto Fujiwara and Camden Lopez and Tracey L Marsh and Indu Raman and Cesia A Marquez and Subhojit Paul and Sumit K Mishra and Naoto Kubota and Courtney Katz and Hiroaki Kanzaki and Michael Gonzalez and Lisa Quirk and Sneha Deodhar and Pratibha Selvakumar and Prithvi Raj and Neehar D Parikh and Lewis R Roberts and Myron E Schwartz and Mindie H Nguyen and Alex S Befeler and Stephanie Page-Lester and Sudhir Srivastava and Ziding Feng and K Rajender Reddy and Saira Khaderi and Sumeet K Asrani and Fasiha Kanwal and Hashem B El-Serag and Jorge A Marrero and Amit G Singal and Yujin Hoshida},

doi = {10.1053/j.gastro.2024.10.035},

issn = {1528-0012},

year  = {2025},

date = {2025-03-01},

journal = {Gastroenterology},

volume = {168},

number = {3},

pages = {556--567.e7},

abstract = {BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.nnMETHODS: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.nnRESULTS: Of 2156 patients with cirrhosis in the Texas HCC Consortium, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared with low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios for incident HCC of 7.51 (95% CI, 4.42-12.8) and 4.20 (95% CI, 2.52-7.01), respectively. Of 1328 patients with cirrhosis in the HCC early detection strategy, PAaM identified 201 high-risk (15%), 540 intermediate-risk (41%), and 587 low-risk (44%) patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate-risk groups were associated with sub-distribution hazard ratios for incident HCC of 6.54 (95% CI, 3.85-11.1) and 1.77 (95% CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease and cured hepatitis C infection.nnCONCLUSIONS: PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}