Journal of Gastroenterology最新文献

{"title":"An integrative multi-omics analysis reveals a multi-analyte signature of pancreatic ductal adenocarcinoma in serum.","authors":"Rex Devasahayam Arokia Balaya, Partho Sen, Caroline W Grant, Roman Zenka, Marimuthu Sappani, Jeyaseelan Lakshmanan, Arjun P Athreya, Richard K Kandasamy, Akhilesh Pandey, Seul Kee Byeon","doi":"10.1007/s00535-024-02197-6","DOIUrl":"10.1007/s00535-024-02197-6","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC.</p><p><strong>Methods: </strong>We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC.</p><p><strong>Results: </strong>We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites.</p><p><strong>Conclusions: </strong>Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"496-511"},"PeriodicalIF":6.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813338","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":"Factors associated with the development of bacterial pneumonia and the preventive potential of peroral endoscopic myotomy in patients with esophageal motility disorders: a case-control study.","authors":"Hitomi Hori, Hirofumi Abe, Shinwa Tanaka, Hiroya Sakaguchi, Kazunori Tsuda, Chise Ueda, Fumiaki Kawara, Takashi Toyonaga, Masato Kinoshita, Satoshi Urakami, Tatsuya Nakai, Shinya Hoki, Hiroshi Tanabe, Yuzo Kodama","doi":"10.1007/s00535-025-02238-8","DOIUrl":"https://doi.org/10.1007/s00535-025-02238-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with esophageal motility disorders (EMDs) sometimes develop bacterial pneumonia (BP). However, factors associated with BP in patients with EMDs and whether peroral endoscopic myotomy (POEM) reduces BP development are unclear. Therefore, this study aimed to identify factors associated with BP development and evaluate the preventive potential of POEM in patients with EMDs.</p><p><strong>Methods: </strong>This study included 623 patients diagnosed with EMDs at our institution between April 2015 and March 2023. Factors associated with BP were analyzed by comparing characteristics between patients who developed BP within 1 year before diagnosis using multivariable analysis. The potential of POEM to prevent BP development was assessed using Cox regression analysis, considering treatment status as a time-varying covariate.</p><p><strong>Results: </strong>Of the 623 patients, 31 (5.0%) developed BP within 1 year before diagnosis. Older age (odds ratio [OR] = 1.29, 95% confidence interval [CI] 1.04-1.59, p = 0.019; 10-year increments), lower body mass index (OR = 0.87, 95% CI 0.78-0.98, p = 0.026), and manometric diagnosis of spastic esophageal disorders (OR = 2.97, 95% CI 1.24-7.16, p = 0.015) were significantly associated with BP. Treatment status of POEM was proved to be a significant factor for developing BP using Cox regression analysis (hazard ratio = 0.17, 95% CI 0.039-0.75, p = 0.019).</p><p><strong>Conclusions: </strong>Risk factors associated with BP in patients with EMDs were older age, lower body mass index, and manometric diagnosis of spastic esophageal disorders. POEM could decrease spasm-related bolus reflux, improve patients' nutritional status through resolution of transit disturbance, and reduce respiratory complications, suggesting that POEM could help prevent BP development.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700544","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":"Liver fibrotic burden across the spectrum of hypothyroidism.","authors":"Tingting Du, Yuchai Huang, Yongman Lv, Gang Yuan","doi":"10.1007/s00535-024-02184-x","DOIUrl":"10.1007/s00535-024-02184-x","url":null,"abstract":"<p><strong>Background: </strong>Data regarding the prevalence of hepatic fibrotic burden across the spectrum of hypothyroidism are scarce. Hence, we aimed to evaluate the prevalence of liver fibrotic burden across the spectrum of hypothyroidism.</p><p><strong>Methods: </strong>30,091 individuals who attended a Health Management Centre between 2019 and 2021 were cross-sectionally analyzed. Participants were categorized as having strict-normal thyroid function, low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism. Hepatic fibrosis was assessed by vibration-controlled transient elastography (VCTE). Significant and advanced fibrosis were defined as liver stiffness measurement in VCTE of 8.1-9.6 and 9.7-13.5 kPa, respectively.</p><p><strong>Results: </strong>Among both men and women, low-normal thyroid function group, subclinical hypothyroidism group, and overt hypothyroidism group all have more liver fibrosis present, including mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, than the strict-normal thyroid function group. The low-normal thyroid function group have the similar liver fibrotic burden to the subclinical hypothyroidism group. The highest liver fibrotic burden was noted in the overt hypothyroidism group. Both significant and advanced liver fibrosis were significantly associated with low-normal thyroid function, subclinical hypothyroidism, and overt hypothyroidism in both men and women.</p><p><strong>Conclusions: </strong>Liver fibrotic burden are highly prevalent in subjects with overt hypothyroidism. Moreover, fibrotic burden increased across the spectrum of hypothyroidism even within the low normal thyroid function. These results suggested that screening for liver fibrosis in patients with hypothyroidism is necessary.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"315-327"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729602","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":"Cox proportional hazards regression reveals more than a 100-fold difference in cancer risk by the length of Barrett's esophagus in Japan.","authors":"Katsunori Iijima, Sho Fukuda, Kenta Watanabe","doi":"10.1007/s00535-024-02208-6","DOIUrl":"10.1007/s00535-024-02208-6","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"387-388"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006557","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":"Acknowledgements.","authors":"","doi":"10.1007/s00535-025-02229-9","DOIUrl":"10.1007/s00535-025-02229-9","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"392-395"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468308","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":"YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway.","authors":"Xiyu Wu, Kohei Yamashita, Chihiro Matsumoto, Weiliyun Zhang, Ming Ding, Kazuto Harada, Keisuke Kosumi, Kojiro Eto, Satoshi Ida, Yuji Miyamoto, Masaaki Iwatsuki","doi":"10.1007/s00535-024-02180-1","DOIUrl":"10.1007/s00535-024-02180-1","url":null,"abstract":"<p><strong>Background: </strong>Although imatinib (IM) and subsequent tyrosine kinase inhibitors (TKIs) significantly improve the prognosis of GIST patients by delaying metastasis and recurrence, most patients experience limited efficacy due to toxicity and secondary resistance. We evaluated Yes-associated protein (YAP), a coactivator of the Hippo pathway accounting for IM resistance and aggressive GIST phenotypes, in GISTs. The degradation of YAP is mediated by FBXW7, and FBXW7 predicts recurrence and IM efficacy for GIST patients. Here, we aimed to identify the potential of YAP as a prognostic marker for patients with GISTs, and the molecular mechanism of FBXW7-YAP pathway in GIST cells.</p><p><strong>Methods: </strong>We measured YAP expression in 167 GIST cases using immunohistochemical staining, correlated its expression levels with clinicopathological features, and the molecular mechanism underlying the FBXW7-YAP pathway was further examined in vitro and in vivo.</p><p><strong>Results: </strong>Compared to 80 (47.9%) cases in the low YAP expression group, 87 (52.1%) cases with high YAP expression associated with a poorer prognosis in terms of overall survival (P = 0.004) and recurrence-free survival (P = 0.003). YAP expression was identified as a significant independent factor affecting the 5-year overall survival (P = 0.005) and recurrence-free survival rates (P = 0.007). Moreover, YAP was directly targeted by FBXW7 to affect proliferation, invasion, and migration in GIST cells. High YAP expression correlated with FBXW7 deficiency, as shown in xenograft and metastasis mouse models.</p><p><strong>Conclusions: </strong>YAP expression serves as a predictive marker of recurrence for GIST patients with curative resection, highlighting its potential as a novel therapeutic target that warrants further investigation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"275-284"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668300","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":"Validation of the Japanese version of the Esophageal Hypervigilance and Anxiety Scale for esophageal symptoms.","authors":"Akinari Sawada, Yoshimasa Hoshikawa, Hiroko Hosaka, Masahiro Saito, Hirotaka Tsuru, Shunsuke Kato, Eikichi Ihara, Tomoyuki Koike, Toshio Uraoka, Kunio Kasugai, Katsuhiko Iwakiri, Daniel Sifrim, John Erik Pandolfino, Tiffany H Taft, Yasuhiro Fujiwara","doi":"10.1007/s00535-024-02193-w","DOIUrl":"10.1007/s00535-024-02193-w","url":null,"abstract":"<p><strong>Background: </strong>The Esophageal Hypervigilance and Anxiety Scale (EHAS) is an English questionnaire created in the USA to assess these factors in all patients with esophageal diseases. The aim of this study was to develop and validate the Japanese version of EHAS and investigate the relationship between EHAS scores and symptoms in untreated disorders of esophagogastric junction (EGJ) outflow.</p><p><strong>Methods: </strong>This prospective study recruited patients who underwent high-resolution manometry (HRM) at six tertiary centers in Japan. The EHAS was translated to Japanese using standard forward and backward translation methods. Patients completed the following questionnaires: the Japanese EHAS, Eckardt score, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for assessment of construct validity. Logistic regression analysis identified factors associated with esophageal symptom severity in untreated disorders of EGJ outflow.</p><p><strong>Results: </strong>Overall, we analyzed 432 patients. Their main symptoms were dysphagia and reflux. The most common HRM diagnosis was normal (35.9%), followed by achalasia (29.4%). The Japanese EHAS demonstrated excellent reliability, and construct validity, with two subscales similar to the original EHAS. Total EHAS score moderately correlated to Eckardt score (r = 0.545, p < 0.001). In 113 patients with untreated disorders of EGJ outflow, multivariable analysis demonstrated that younger age, type II achalasia, and higher EHAS score were independently associated with higher Eckardt score.</p><p><strong>Conclusions: </strong>The Japanese EHAS is a reliable and valid questionnaire. Its subscale scores can be used as in the original version with some caution. Future studies are warranted to assess the appropriateness of factor loading.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"265-274"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801096","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":"Refining risk assessment in Barrett's esophagus: addressing follow-up and diagnostic limitations.","authors":"Jing Jia, Ying He, Ling Hu","doi":"10.1007/s00535-024-02207-7","DOIUrl":"10.1007/s00535-024-02207-7","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"385-386"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921077","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":"Revisiting the relationship between thyroid function and metabolic dysfunction-associated steatotic liver disease in the era of resmetirom.","authors":"Sadatsugu Sakane, Hayato Hikita","doi":"10.1007/s00535-025-02214-2","DOIUrl":"10.1007/s00535-025-02214-2","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"389-391"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023650","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":"Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors.","authors":"Shinji Okabayashi, Takahiro Itaya, Hajime Yamazaki, Ryo Yanai, Masaaki Isshiki, Yosuke Yamamoto","doi":"10.1007/s00535-024-02190-z","DOIUrl":"10.1007/s00535-024-02190-z","url":null,"abstract":"<p><strong>Background: </strong>The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi.</p><p><strong>Methods: </strong>A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16 years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment.</p><p><strong>Results: </strong>We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]).</p><p><strong>Conclusions: </strong>There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"285-293"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785951","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}