Journal of Gastroenterology最新文献

{"title":"Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.","authors":"Marwa M Abu-Serie, Ana K Gutiérrez-García, Macie Enman, Utpreksha Vaish, Huma Fatima, Vikas Dudeja","doi":"10.1007/s00535-025-02213-3","DOIUrl":"10.1007/s00535-025-02213-3","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and exhibits a limited response to apoptosis-dependent chemotherapeutic drugs (e.g., gemcitabine, Gem). This is mainly attributed to the antioxidant defense system (glutathione and aldehyde dehydrogenase (ALDH) 1A1), which sustains stemness features of cancer stem cells (CSCs) and activated pancreatic stellate cells (PSCs)-generated excess stromal proteins. This dense stroma retards drug delivery.</p><p><strong>Methods: </strong>This study established co-spheroid model consisting of mouse PDAC cell line (KPC) and PSCs (1:5) to accurately investigate the anti-PDAC activity of nanocomplex of ferrous oxide nanoparticles-diethyldithiocarbamate (FeO NPs-DE), compared to Gem, using in vitro and in vivo 3D models.</p><p><strong>Results: </strong>In vitro and in vivo co-spheroid models demonstrated higher therapeutic efficacy of FeO NPs-DE than Gem. FeO NPs-DE induced selective accumulation of iron-dependent ferroptosis (non-apoptosis)-generated a lethal lipid peroxidation that was potentiated by DE-mediated glutathione and ALDH1A1 suppression. This led to collapse of stemness, as evidenced by down-regulating CSC genes and p-AKT protein expression. Subsequently, gene and/or protein levels of PSC activators (transforming growth factor (TGF)-β, plasminogen activator inhibitor-1, ZEB1, and phosphorylated extracellular signal-regulated kinase) and stromal proteins (collagen 1A2, smooth muscle actin, fibronectin, and matrix metalloproteinase-9) were suppressed. Moreover, DE of nanocomplex enhanced caspase 3-dependent apoptosis with diminishing the main oncogene, BCL-2.</p><p><strong>Conclusions: </strong>FeO NPs-DE had a stronger eradicating effect than Gem on primary and metastatic peritoneal PDAC tumors. This nanocomplex-mediated ferroptosis and stemness inhibition provides an effective therapeutic approach for PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"641-657"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel.","authors":"Muneyori Okita, Kento Takenaka, Fumihito Hirai, Shinya Ashizuka, Hideki Iijima, Shigeki Bamba, Toshimitsu Fujii, Kenji Watanabe, Yosuke Shimodaira, Hisashi Shiga, Sakiko Hiraoka, Toshihiro Inokuchi, Takeshi Yamamura, Ryo Emoto, Shigeyuki Matsui","doi":"10.1007/s00535-025-02223-1","DOIUrl":"10.1007/s00535-025-02223-1","url":null,"abstract":"<p><strong>Background: </strong>Small bowel (SB) lesions in Crohn's disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.</p><p><strong>Methods: </strong>This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.</p><p><strong>Results: </strong>Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65-0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).</p><p><strong>Conclusion: </strong>LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"573-582"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent body-weight change on achalasia and peroral endoscopic myotomy: a multicenter cohort study.","authors":"Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Takuya Satomi, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue","doi":"10.1007/s00535-024-02205-9","DOIUrl":"10.1007/s00535-024-02205-9","url":null,"abstract":"<p><strong>Background: </strong>The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear.</p><p><strong>Methods: </strong>Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m²) and overweight (BMI ≥ 25.0 kg/m²) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated.</p><p><strong>Results: </strong>Among 3,410 patients, 23.0% and 15.7% were underweight and overweight, respectively. Factors associated with underweight were higher age, female sex, severe symptoms, high lower esophageal sphincter (LES) pressure, and non-dilated esophagus (all p < 0.01). Longitudinal analyses revealed that weight gain post-POEM was achieved after a long duration (≥ 12 months; p < 0.01). In 528 patients post-POEM, the frequency of underweight reduced to 8.3% (p < 0.01). Risk factors for insufficient-weight gain (36.1% of underweight patients) included low BMI (p < 0.01) and high LES pressure (p = 0.03) and conversely for excessive-weight gain. Machine learning models based on patient characteristics successfully predicted insufficient- and excessive-weight gainers with an area under the curve value of 0.74 and 0.75, respectively. Esophageal symptoms post-POEM did not correlate with BMI increase.</p><p><strong>Conclusion: </strong>Underweight is not solely a condition of advanced achalasia. After POEM, insufficient- or excessive-weight gainers are not rare and can be predicted preoperatively. Body weight change is an independent nutrition parameter rather than a part of the assessment of residual esophageal symptoms.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"535-545"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controversy regarding the risk of autoimmune gastritis on gastric adenocarcinoma.","authors":"Nobutake Yamamichi, Rika Aoki","doi":"10.1007/s00535-025-02245-9","DOIUrl":"10.1007/s00535-025-02245-9","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"671-672"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.","authors":"Xiaoli Zhang, Jianzhou Li, Yichen Yao, Mimi Zhou, Yingli He, Yalei Zhao","doi":"10.1007/s00535-025-02212-4","DOIUrl":"10.1007/s00535-025-02212-4","url":null,"abstract":"<p><strong>Background: </strong>We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes.</p><p><strong>Results: </strong>Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4^high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions.</p><p><strong>Conclusions: </strong>TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"593-606"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The external validation of Dallas Steatosis Index among Asian population: a useful tool for metabolic dysfunction-associated steatotic liver disease identification and prevention.","authors":"Mengyang Xia, Yixuan Lu, Feiyang Yin, Zhiqiang Cao, Ping Yao, Hongxia Li","doi":"10.1007/s00535-025-02220-4","DOIUrl":"10.1007/s00535-025-02220-4","url":null,"abstract":"<p><strong>Background: </strong>The Dallas Steatosis Index (DSI) is a non-invasive tool (NIT) developed to detect the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in multi-ethnic populations, external validation in Asians has yet to be conducted. Therefore, we evaluated the ability of the DSI with the BMI classification of WPRO (DSI_WPRO) to identify MASLD in the Chinese population. In addition, we investigated the associations between the DSI_WPRO and the risk of MASLD in a longitudinal study.</p><p><strong>Methods: </strong>Baseline data from the Dongfeng-Tongji cohort were collected to investigate the ability of the DSI_WPRO to identify MASLD patients by ROC analysis. Furthermore, multivariate logistic regressions were performed to investigate the associations of the DSI_WPRO and MASLD risks in a 5-year follow-up of the DFTJ cohort study.</p><p><strong>Results: </strong>Among a total of 9,376 MASLD participants and 25,974 non-MASLD participants, the area under the curve (AUC) of the DSI_WPRO reached 0.777 after adjusting BMI classification, which is higher than other NITs in this study. In addition, we redefined the risk category and the screening proposal of MASLD in Asians with the DSI_WPRO. We found that the cutoff point of 0 has the best ability to recognize the presence or absence of MASLD. Furthermore, compared with the low DSI_WPRO (DSI_WPRO < 0), OR (95% CIs) of higher DSI_WPRO (DSI_WPRO ≥ 0) was 3.048 (2.827 ~ 3.285) for MASLD.</p><p><strong>Conclusion: </strong>The DSI is a useful tool for MASLD identification and prevention. After more validation studies, DSI can be generalized in the Asian population.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"621-631"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain activity during a public-speaking situation in virtual reality in patients with irritable bowel syndrome and functional dyspepsia.","authors":"Ryo Katsumata, Takayuki Hosokawa, Noriaki Manabe, Hitoshi Mori, Kenta Wani, Minako Kimura, Shintaro Oda, Katsunori Ishii, Tomohiro Tanikawa, Noriyo Urata, Maki Ayaki, Ken Nishino, Takahisa Murao, Mitsuhiko Suehiro, Minoru Fujita, Miwa Kawanaka, Ken Haruma, Hirofumi Kawamoto, Toshihiro Takao, Tomoari Kamada","doi":"10.1007/s00535-025-02228-w","DOIUrl":"10.1007/s00535-025-02228-w","url":null,"abstract":"<p><strong>Background: </strong>Psychosocial stress plays a central role in the pathophysiology of disorders of gut-brain interactions (DGBI), including functional dyspepsia (FD) and irritable bowel syndrome (IBS). Brain activity during psychosocial stress in patients with DGBI has not been adequately investigated. In this prospective study, we aimed to explore brain activity during psychosocial stress in patients with DGBI.</p><p><strong>Methods: </strong>Situations in an unmanned room, public space without attention, and public speaking were simulated in a virtual reality (VR) environment. Subjective stress, emotional state, and gastrointestinal (GI) symptoms were assessed using a visual analog scale, the State-Trait Anxiety Inventory, and the GI Symptom Rating Scale, respectively. Electrocardiograms were recorded to evaluate autonomic function. Activity in the prefrontal cortex (PFC) was examined using functional near-infrared spectroscopy (fNIRS).</p><p><strong>Results: </strong>Overall, 15 healthy controls, 15 patients with IBS, and 15 patients with FD were included. In the public-speaking scenario, subjective stress scores significantly decreased (indicating more stress) and sympathetic nervous activity increased equally among the three groups compared with those in an unmanned scene. Patients with IBS had higher activity in the left ventrolateral prefrontal cortex (VLPFC) and lower activity in the dorsolateral PFC (DLPFC) than those with FD and healthy controls.</p><p><strong>Conclusions: </strong>Brain activity increased in the VLPFC and decreased in the DLPFC under stressful psychosocial situations created in the VR space in patients with IBS. Thus, the combination of VR and fNIRS is a viable option for evaluating brain activity under psychosocial stress in natural clinical settings.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"561-572"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of epithelial types on postoperative outcomes for intraductal papillary mucinous neoplasms: a multicenter retrospective study.","authors":"Daiki Yamashige, Susumu Hijioka, Yasuhiro Shimizu, Akio Yanagisawa, Masafumi Nakamura, Kazuo Hara, Masayuki Kitano, Shinsuke Koshita, Tetsuya Takikawa, Toshifumi Kin, Mamoru Takenaka, Keiji Hanada, Toshiharu Ueki, Takao Itoi, Reiko Yamada, Takao Ohtsuka, Seiko Hirono, Atsushi Kanno, Yoshifumi Takeyama, Atsushi Masamune","doi":"10.1007/s00535-025-02225-z","DOIUrl":"10.1007/s00535-025-02225-z","url":null,"abstract":"<p><strong>Background: </strong>Intraductal papillary mucinous neoplasms (IPMNs) are classified into three epithelial types with distinct biological behaviors. However, their effects on the postoperative outcomes remain unclear.</p><p><strong>Methods: </strong>This multicenter retrospective study included 556 patients with IPMNs who underwent surgical resection. The epithelial types were categorized into the gastric (n = 323), intestinal (n = 160), and pancreatobiliary (n = 73) types. Their associations with the development of extrapancreatic lesions; remnant high-risk lesions (HRLs), including metachronous pancreatic ductal adenocarcinoma (PDAC); and disease-specific survival (DSS) were analyzed.</p><p><strong>Results: </strong>Fifty-one patients (9.2%) developed extrapancreatic lesions. The 10-year cumulative incidence rates for the gastric, intestinal, and pancreatobiliary types were 9.3%, 9.1%, and 32.0%, respectively (P < 0.001). Multivariate analysis identified invasive carcinoma, the gastric, and pancreatobiliary types as independent predictors. Among 516 patients who did not undergo total pancreatectomy, 40 (7.8%) and 13 (2.5%) developed HRLs and metachronous PDAC, respectively. The 10-year cumulative incidence rates of HRLs and metachronous PDAC for the gastric, intestinal, and pancreatobiliary types were 7.0%, 16.2%, and 37.2% and 1.8%, 3.7%, and 22.7%, respectively (P = 0.001 and P = 0.012). In multivariate analysis, the pancreatobiliary type was an independent predictor of metachronous PDAC. Five-year DSS rates for the gastric, intestinal, and pancreatobiliary types were 92.5%, 96.0%, and 76.1% (P < 0.001), respectively. Multivariate analysis identified invasive carcinoma, the gastric, and pancreatobiliary types as independent prognostic factors for DSS.</p><p><strong>Conclusions: </strong>IPMN epithelial type can independently affect postoperative outcomes. In particular, the pancreatobiliary type has significant impact on the development of metachronous PDAC. Therefore, postoperative surveillance should be tailored according to the epithelial type.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"658-670"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldh2 and the tumor suppressor Trp53 play important roles in alcohol-induced squamous field cancerization.","authors":"Yuki Kondo, Shinya Ohashi, Chikatoshi Katada, Yukie Nakai, Yoshihiro Yamamoto, Masashi Tamaoki, Osamu Kikuchi, Atsushi Yamada, Kenshiro Hirohashi, Yosuke Mitani, Shigeki Kataoka, Tomoki Saito, Trang H Nguyen Vu, Tomohiro Kondo, Yu Uneno, Tomohiko Sunami, Akira Yokoyama, Junichi Matsubara, Tomonari Matsuda, Seiji Naganuma, Kohei Oryu, Samuel Flashner, Masataka Shimonosono, Hiroshi Nakagawa, Manabu Muto","doi":"10.1007/s00535-024-02210-y","DOIUrl":"10.1007/s00535-024-02210-y","url":null,"abstract":"<p><strong>Background: </strong>Field cancerization defined by multiple development of squamous cell carcinomas (SCCs) in upper aerodigestive tract was explained by excessive alcohol intake. A dysfunctional mitochondrial aldehyde dehydrogenase 2 (Aldh2) delays the clearance of acetaldehyde, a genotoxic alcohol metabolite, and increases SCC risks. TP53 plays key roles in squamous carcinogenesis. However, the mechanism of alcohol-mediated squamous field cancerization has not been clearly elucidated.</p><p><strong>Methods: </strong>We developed a novel genetically engineered mouse strain KTPA^-/- (Krt5Cre^ERT2; Trp53^loxp/loxp; Aldh2^-/-) featuring Aldh2-loss concurrent with epithelial-specific Trp53 deletion. These mice were given 10%-EtOH, and we evaluated the development of squamous cell carcinogenesis histologically and genetically.</p><p><strong>Results: </strong>Widespread multifocal rete ridges (RRs), characterized by downward growth of proliferative preneoplastic cells, were found only in Aldh2^+/- and Aldh2^-/- mice with keratin5-specific Trp53 deletion (KTPA^+/- and KTPA^-/- mice, respectively), and alcohol drinking apparently increased RR formation rate. SCC occurred only in KTPA^-/- (Aldh2 loss/TP53 loss) mice with alcohol drinking (15/18: 83%). Total alcohol consumption volume was significantly higher in KTPA^-/- (Aldh2 loss/TP53 loss) mice with SCCs than those without SCCs. Further, target sequence revealed the occurrence of genetic abnormalities including Trp53 mutations in the esophageal epithelium of Aldh2^-/- mice with alcohol drinking, suggesting direct mutagenic effects of alcohol drinking to the esophageal epithelium.</p><p><strong>Conclusion: </strong>This study provides for the first time the evidence that alcohol drinking, Aldh2 dysfunction and Trp53 loss cooperate in squamous field cancerization. Alcohol consumption volume affects the SCCs development, even in the same genotype.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"546-560"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A clinicopathological study of IgG4-related autoimmune hepatitis and IgG4-hepatopathy.","authors":"Atsushi Tanaka, Kenji Notohara, Maki Tobari, Masanori Abe, Takeji Umemura, Atsushi Takahashi, Akemi Tsutsui, Takanori Ito, Kohichi Tsuneyama, Atsushi Masamune, Ken-Ichi Harada, Hiromasa Ohira, Mitsuhiro Kawano","doi":"10.1007/s00535-025-02221-3","DOIUrl":"10.1007/s00535-025-02221-3","url":null,"abstract":"<p><strong>Background and aim: </strong>Although IgG4-related autoimmune hepatitis (IgG4-AIH) and IgG4-hepatopathy have been proposed as hepatic phenotypes of IgG4-related disease (IgG4-RD), their definitions and concepts remain insufficiently established. This study aims to conduct a clinicopathological investigation of cases reported as potential IgG4-AIH or IgG4-hepatopathy.</p><p><strong>Methods: </strong>In previous nationwide epidemiological studies conducted in 2015 and 2018, we registered 1096 cases of IgG4-sclerosing cholangitis (IgG4-SC). Among these, 19 cases were identified as potential IgG4-AIH by the attending physicians, and other 20 cases as potential IgG4-hepatopathy with available liver histology were further evaluated using immunohistochemistry to assess the possibility of IgG4-AIH or IgG4-hepatopathy. For this purpose, we provisionally established diagnostic criteria for IgG4-AIH and IgG4-hepatopathy, primarily based on the comprehensive diagnostic criteria for IgG4-RD, which include IgG4 + cell count > 10/HPF and an IgG4 + /IgG ratio > 40%.</p><p><strong>Results: </strong>Of the 19 cases, 2 were diagnosed as IgG4-AIH, with IgG4 + cell counts/HPF of 25.3 and 18.7, and IgG4 + /IgG ratios of 310.2% and 53.4%, respectively. Neither storiform fibrosis nor obliterative phlebitis was observed in the liver of these cases, and both responded excellently to corticosteroid treatment. In addition, from other 20 cases, we diagnosed 8 cases as IgG4-hepatopathy, with IgG4-SC and autoimmune pancreatitis being present in 7 and 2 cases, respectively.</p><p><strong>Conclusion: </strong>This study identified two cases of IgG4-AIH and eight cases of IgG4-hepatopathy. Further studies are necessary to explore the occurrence of IgG4-AIH using these diagnostic criteria in the AIH cohort. The presence of IgG4-hepatopathy may facilitate the diagnosis of IgG4-SC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"632-640"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}