Journal of Gastroenterology最新文献

{"title":"Temporal trends in obesity and its prognostic impact in Korean patients with inflammatory bowel disease.","authors":"Min Kyu Kim, Seung Hwan Shin, Cheol-Hyung Lee, Soyoung Kim, Jong Whan Kim, Songhyun Lee, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Sung Wook Hwang","doi":"10.1007/s00535-025-02230-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02230-2","url":null,"abstract":"<p><strong>Background: </strong>To assess the changes in body mass index (BMI) among Korean patients with inflammatory bowel disease (IBD) over a 14-year period and to explore how BMI at diagnosis impacts prognosis.</p><p><strong>Methods: </strong>We retrospectively collected BMI and laboratory data from patients with IBD who visited the Asan Medical Center between 2008 and 2021 (Cohort 1). Clinical outcomes, including intestinal resection and medication use, were analyzed in patients with a recorded BMI at diagnosis who were followed up in a prospectively maintained cohort (Cohort 2).</p><p><strong>Results: </strong>Among 11,216 IBD patients (Cohort 1), the median BMI increased over the study period, and the disparity in the prevalence of obese individuals (BMI ≥ 25 kg/m²) between those with IBD and the general population narrowed. Serum glucose and lipid profiles showed an upward trend during the study period. In patients with recorded BMI at the time of diagnosis (Cohort 2), the odds of intestinal resection and the use of biologics/small molecules were comparable or even lower in Crohn's disease (CD) and ulcerative colitis patients who were obese compared to patients with a normal BMI. Obesity (≥ 25 kg/m²) was inversely associated with the risk of thiopurine use in CD patients (adjusted hazard ratio: 0.61, 95% confidence interval: 0.48-0.78, p < 0.001).</p><p><strong>Conclusions: </strong>During a 14-year period, Korean IBD patients showed increasing trends in the prevalence of obese individuals and metabolic syndrome-associated laboratory results. CD patients with high BMI at diagnosis exhibited a similar or lower likelihood of undergoing intestinal resection and medication use compared to those with a normal BMI.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501868","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":"https://doi.org/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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-24","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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-24","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":"Diagnostic performance of attenuation imaging versus controlled attenuation parameter for hepatic steatosis with MRI-based proton density fat fraction as the reference standard: a prospective multicenter study.","authors":"Takashi Nishimura, Toshifumi Tada, Tomoyuki Akita, Reiichiro Kondo, Yasuaki Suzuki, Kento Imajo, Shigehiro Kokubu, Tamami Abe, Hidekatsu Kuroda, Masashi Hirooka, Yoichi Hiasa, Asako Nogami, Atsushi Nakajima, Sadanobu Ogawa, Hidenori Toyoda, Satoshi Oeda, Hirokazu Takahashi, Yuichiro Eguchi, Katsutoshi Sugimoto, Hirohisa Yano, Junko Tanaka, Fuminori Moriyasu, Masayoshi Kage, Takashi Kumada, Hiroko Iijima","doi":"10.1007/s00535-025-02224-0","DOIUrl":"https://doi.org/10.1007/s00535-025-02224-0","url":null,"abstract":"<p><strong>Background: </strong>Attenuation Imaging (ATI) and controlled attenuation parameter (CAP) are non-invasive ultrasound-based methods for diagnosing hepatic steatosis. However, reports on the clinical usefulness of ATI are limited. We aimed to compare the ability of ATI and CAP to diagnose hepatic steatosis with magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as the reference standard.</p><p><strong>Methods: </strong>We performed a prospective multicenter study of 562 patients with chronic liver disease who underwent ATI, CAP, and MRI-PDFF. Patients with skin-to-liver capsule distance (SCD) ≤ 25 mm underwent CAP with an M probe; those with SCD > 25 mm underwent CAP with an XL probe. MRI-PDFF was used as the reference standard: S0 corresponds to MRI-PDFF < 5.2%, S1 to 5.2% ≤ MRI-PDFF < 11.3%, S2 to 11.3% ≤ MRI-PDFF < 17.1%, and S3 to MRI-PDFF ≥ 17.1%.</p><p><strong>Results: </strong>The correlation coefficients for ATI and MRI-PDFF stratified by body mass index (< 30, ≥ 30 kg/m²), SCD (< 25, ≥ 25 mm), 2-dimensional share wave elastography (< 1.8 m/s), fibrosis-4 index (≤ 2.67), albumin-bilirubin score (< - 2.60) and type IV collagen 7 s (< 5.0 ng/ml) were significantly higher than those for CAP and MRI-PDFF. Areas under the receiver operating characteristics (95% CI) for ATI and CAP were 0.895 (0.869-0.922) and 0.845 (0.809-0.881) for ≥ S1 steatosis, 0.944 (0.926-0.963) and 0.881(0.852-0.910) for ≥ S2 steatosis, and 0.928 (95% CI 0.906-0.950) and 0.860 (95% CI 0.829-0.890) for S3 steatosis. ATI had higher diagnostic performance for all hepatic steatosis grades than CAP.</p><p><strong>Conclusions: </strong>ATI is a more useful non-invasive method for diagnosing hepatic steatosis than CAP.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482738","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":"https://doi.org/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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","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":"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":"https://doi.org/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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age distribution and risk factors for Barrett's esophagus by sex at health check-up settings in Japan.","authors":"Sho Fukuda, Kenta Watanabe, Dai Kubota, Nobutake Yamamichi, Yu Takahashi, Yoshitaka Watanabe, Kyoichi Adachi, Norihisa Ishimura, Tomoyuki Koike, Hideyuki Sugawara, Kiyotaka Asanuma, Yasuhiko Abe, Takashi Kon, Eikichi Ihara, Kazuhiro Haraguchi, Yoshihiro Otsuka, Rie Yoshimura, Yugo Iwaya, Takuma Okamura, Noriaki Manabe, Akira Horiuchi, Mio Matsumoto, Kengo Onochi, So Takahashi, Tatsuki Yoshida, Yosuke Shimodaira, Katsunori Iijima","doi":"10.1007/s00535-025-02222-2","DOIUrl":"https://doi.org/10.1007/s00535-025-02222-2","url":null,"abstract":"<p><strong>Background: </strong>Given the high prevalence of esophageal adenocarcinoma and Barrett's esophagus (BE), a precancerous lesion, among males, it is important to understand the characteristics of BE by sex to develop an effective endoscopic surveillance program in Japan. The present study examined the age distribution and risk factors for BE in the Japanese health check-up cohort by sex.</p><p><strong>Methods: </strong>The data set at baseline of our preceding multicenter study, comprising a total of 33,478 individuals who underwent upper endoscopic screening at 17 health check-up institutes across Japan, was utilized. BE and long-segment BE (LSBE) were defined as a columnar-lined esophagus ≥ 1 cm and ≥ 3 cm, respectively. Logistic regression analyses were performed to ascertain the factors associated with BE.</p><p><strong>Results: </strong>BE was relatively common (10-20%) across all 10-year age groups in men and women. Although the prevalence of LSBE was rare (0.2%), it began to increase at younger ages in men. In the multivariable analysis of the male cohort, while body mass index (BMI) was negatively associated with BE with an adjusted odds ratio (95% confidence interval) of 0.84 (0.74-0.95), waist circumference (WC) was positively associated with 1.26 (1.13-1.41). Furthermore, this association was more pronounced in LSBE. In contrast, no such association was observed between BMI or WC and BE in women.</p><p><strong>Conclusion: </strong>The nationwide Japanese multicenter study yielded insights into the age distribution of BE in the Japanese population. Furthermore, our findings indicate that a low BMI/high WC represents a significant risk factor for BE in the Japanese male population.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381258","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":"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":"https://doi.org/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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions and clinical significance of KCNB1 in esophageal squamous cell carcinoma.","authors":"Atsuki Ota, Atsushi Shiozaki, Hiroki Shimizu, Toshiyuki Kosuga, Michihiro Kudou, Keiji Nishibeppu, Takuma Ohashi, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Yukiko Morinaga, Eiichi Konishi, Eigo Otsuji","doi":"10.1007/s00535-025-02219-x","DOIUrl":"https://doi.org/10.1007/s00535-025-02219-x","url":null,"abstract":"<p><strong>Background: </strong>Voltage-gated potassium channel subfamily B member 1 (KCNB1) encodes the α-subunit of the Kv2.1 channel and mediates transmembrane potassium transport. The functions and mechanisms underlying KCNB1 activation have been examined in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, the present study investigated the involvement of KCNB1 in tumor progression and the clinicopathological significance of its expression in ESCC.</p><p><strong>Methods: </strong>Knockdown experiments using KCNB1 small interfering RNA were performed on the human ESCC cell lines, KYSE70 and TE5, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. Gene expression profiles were examined using a microarray analysis. An immunohistochemical (IHC) analysis was performed on 129 primary tumor samples from ESCC patients who underwent curative esophagectomy.</p><p><strong>Results: </strong>Cell proliferation, G₂-M phase progression, migration, and invasion were inhibited, and apoptosis was induced in KCNB1-depleted cells. Microarray results showed that KCNB1 gene expression affected Ephrin receptor signaling by suppressing EPHB1, EPHB2, and ERK1/2 gene expression. IHC results revealed a relationship between high KCNB1 expression and a poor prognosis. High KCNB1 expression was extracted as an independent prognostic factor in a multivariate analysis of 5-year relapse-free survival in ESCC patients (p = 0.0197).</p><p><strong>Conclusions: </strong>Cell proliferation is controlled by KCNB1 through its regulation of ERK1/2 gene expression via ephrin receptor signaling. A relationship was observed between KCNB1 and the prognosis of ESCC patients, indicating its potential as a biomarker for cancer progression and in targeted therapy for ESCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074441","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}