Gastro hep advances最新文献

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Gastro hep advances

Pub Date : 2026-01-01

引用次数: 0

Gastro hep advances

Pub Date : 2026-01-01

引用次数: 0

Gastro hep advances

Pub Date : 2026-01-01

引用次数: 0

Gastro hep advances

Pub Date : 2026-01-01

引用次数: 0

Gastro hep advances

Pub Date : 2026-01-01

引用次数: 0

Carbonic Anhydrase-IX Is a Specific and Sensitive Theragnostic Target for Imaging and Radioimmunotherapy in Metastatic Colorectal Cancer 碳酸酐酶ix是转移性结直肠癌影像学和放射免疫治疗的特异和敏感的诊断靶点

Gastro hep advances

Pub Date : 2026-01-01 DOI: 10.1016/j.gastha.2025.100871

Dijina Swaroop , Jai Smith , Jessica Van Zuykelom , Asif Noor , Robin A. Wagner , Tamara Vu , Sarah Lee , Alexander G. Heriot , Benjamin Loveday , Kelly Waldeck , Peter D. Roselt , Benjamin Blyth , Paul S. Donnelly , Frédéric Hollande

Background and Aims

Over 40% of colorectal cancer (CRC) patients develop metastatic disease. Their survival outlook is very low, highlighting the urgent need to improve the detection and therapeutic management of metastatic colorectal cancer (mCRC), particularly when metastases are not surgically resectable. Our study aimed to characterize the preclinical utility of targeting carbonic anhydrase IX (CA-IX) for metastasis imaging and for therapeutic purposes in patients with CRC liver metastases.

Methods

CA-IX expression was characterized in 46 liver metastasis samples using RNA sequencing and immunohistochemical staining. We labeled girentuximab, a clinical grade CA-IX antibody, with zirconium-89 ([⁸⁹Zr]Zr) or lutetium-177 ([¹⁷⁷Lu]Lu), and characterized its biodistribution in vivo. Using radiolabeled girentuximab in patient-derived liver metastasis organoids (PDOs) and xenograft models, we then characterized the preclinical utility of CA-IX imaging and therapeutic targeting in mCRC.

Results

CA-IX mRNA and/or protein expression was detected in 87% of CRC liver metastasis samples, with little to no expression in surrounding liver tissue. Both [⁸⁹Zr]Zr- and [¹⁷⁷Lu]Lu-girentuximab exhibited excellent biodistribution characteristics in mice xenografted with PDOs. Positron emission tomography imaging showed that [⁸⁹Zr]Zr-girentuximab enabled specific and high-resolution detection of CA-IX-expressing lesions at subcutaneous and hepatic sites compared to [¹⁸F]F-fluoro deoxy-glucose. Finally, single-dose [¹⁷⁷Lu]Lu-girentuximab treatment induced cytotoxicity in PDOs in vitro and strongly reduced tumor burden in 2 independent xenografted mouse models, with no signs of toxicity.

Conclusion

Our results demonstrate that CA-IX is a relevant target for a theragnostic strategy in mCRC, and provide the first demonstration in clinically-relevant models of metastasis that radiolabeled girentuximab can be used as a scouting agent to stratify and monitor mCRC patients and as a therapeutic alternative for patients with CA-IX-expressing tumors.

背景和目的超过40%的结直肠癌（CRC）患者发生转移性疾病。他们的生存前景非常低，突出了迫切需要改善转移性结直肠癌（mCRC）的检测和治疗管理，特别是当转移不能手术切除时。我们的研究旨在描述靶向碳酸酐酶IX （CA-IX）在CRC肝转移患者的转移成像和治疗目的中的临床前应用。方法采用RNA测序和免疫组化染色对46例肝转移组织中sca - ix的表达进行检测。我们用锆-89 （[89Zr]Zr）或镥-177 （[177Lu]Lu）标记临床级CA-IX抗体girentuximab，并表征了其在体内的生物分布。在患者源性肝转移类器官（PDOs）和异种移植模型中使用放射标记的吉伦妥昔单抗，我们随后表征了CA-IX成像和治疗靶向在mCRC中的临床前应用。结果87%的结直肠癌肝转移灶中检测到ca - ix mRNA和/或蛋白表达，而周围肝组织中很少或不表达。[89Zr]Zr-和[177Lu]Lu-girentuximab在PDOs异种移植小鼠中均表现出良好的生物分布特性。正电子发射断层成像显示，与[18F] f -氟脱氧葡萄糖相比，[89Zr]Zr-girentuximab能够特异性和高分辨率地检测皮下和肝脏部位表达ca - ix的病变。最后，单剂量[177Lu]Lu-girentuximab在体外诱导PDOs细胞毒性，并在2个独立的异种移植小鼠模型中显著降低肿瘤负荷，无毒性迹象。结论我们的研究结果表明CA-IX是mCRC治疗策略的相关靶点，并首次在临床相关的转移模型中证明放射标记的吉伦妥昔单抗可以作为一种探测剂用于分层和监测mCRC患者，并作为表达CA-IX的肿瘤患者的治疗替代方案。

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引用次数: 0

Iron Deficiency Anemia is Associated With Gastric Intestinal Metaplasia in Patients With Helicobacter pylori Infection 缺铁性贫血与幽门螺杆菌感染患者的胃肠道化生有关

Gastro hep advances

Pub Date : 2026-01-01 DOI: 10.1016/j.gastha.2025.100852

Serach Patterson , Jacqueline Emerson , HannahSofia Brown , Priya Alagesan , Caroline Labriola , Rachel Zuzul , Allison O. Taylor , Danielle L. Mebuge , Nina R. Salama , Wai Yan Min Htike , Frances Wang , Shannon McCall , Katherine S. Garman , Meira Epplein

Background and Aims

Despite acknowledgment of the relationship between iron deficiency anemia (IDA) and Helicobacter pylori, consensus is lacking on clinical practice implications. This study sought to examine the association of iron deficiency and anemia with the precancerous lesion gastric intestinal metaplasia (GIM) in a cohort of patients with active H. pylori infection.

Methods

This retrospective cohort was assembled from adult patients diagnosed with H. pylori at endoscopy at Duke University between 2015 and 2019. Data were collected from pathology reports and electronic health records. The relationship between iron deficiency status and GIM prevalence among 422 H. pylori–positive individuals was examined using age-adjusted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and stratified by diagnosis of H. pylori before the diagnosis at study enrollment.

Results

Of these 422 H. pylori–positive patients, 48.6% had evidence of anemia and/or iron deficiency in the electronic health record. Compared to patients without anemia, those with IDA were more likely to have GIM (OR = 1.66; 95% CI, 1.02–2.69). Fifty-seven patients were previously positive for H. pylori, treated, and remained positive for H. pylori at the index endoscopy, of whom 40% had IDA. Among these patients, those with IDA had 4-fold increased odds of having GIM compared to patients without anemia (OR = 4.11; 95% CI, 1.10–15.32)

Conclusion

In a cohort of H. pylori–positive individuals at endoscopy, those with a history of IDA had greater odds of having GIM compared to patients without anemia. These results suggest the importance of close endoscopic evaluation and sampling of the gastric mucosa to evaluate for GIM in patients with IDA, and particularly those with a previous H. pylori diagnosis.

背景和目的尽管缺铁性贫血（IDA）和幽门螺杆菌之间的关系得到了承认，但在临床实践意义上仍缺乏共识。本研究旨在探讨在一组活动性幽门螺杆菌感染患者中缺铁和贫血与胃癌前病变肠化生（GIM）的关系。方法本回顾性队列研究来自2015年至2019年杜克大学内窥镜检查诊断为幽门螺杆菌的成年患者。数据收集自病理报告和电子健康记录。对422名幽门螺杆菌阳性个体的缺铁状况与GIM患病率之间的关系进行了研究，采用年龄调整logistic回归模型来估计优势比（ORs）和95%置信区间（ci），并根据研究入组时诊断前的幽门螺杆菌诊断进行分层。结果在422例幽门螺杆菌阳性患者中，48.6%的患者在电子健康记录中有贫血和/或缺铁的证据。与没有贫血的患者相比，IDA患者更容易发生GIM （OR = 1.66; 95% CI, 1.02-2.69）。57例患者先前幽门螺杆菌阳性，经治疗后，幽门螺杆菌指数内窥镜检查仍呈阳性，其中40%患有IDA。在这些患者中，IDA患者发生GIM的几率是无贫血患者的4倍（OR = 4.11; 95% CI, 1.10-15.32）。结论在一组内窥镜检查幽门螺杆菌阳性个体中，有IDA病史的患者发生GIM的几率高于无贫血患者。这些结果表明，对于IDA患者，特别是那些先前有幽门螺杆菌诊断的患者，进行近距离内镜评估和胃粘膜取样对于评估GIM的重要性。

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MAM and LDL Receptor Class A Domain Containing 1 Deficiency Aggravates Hepatic Fibrosis in Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis 含1缺陷的MAM和LDL受体A类结构域加重饮食诱导的代谢功能障碍相关脂肪性肝炎的肝纤维化

Gastro hep advances

Pub Date : 2026-01-01 DOI: 10.1016/j.gastha.2025.100854

Jashdeep Bhattacharjee , Linda X. Wang , Brianna Meneses , Juliet A. Emamaullee , Mark R. Frey , Rohit Kohli

引用次数: 0

Alcohol Relapse After Liver Transplantation: Advances in Risk Stratification, Biomarker Integration, and Post-Transplant Care 肝移植后酒精复发：风险分层、生物标志物整合和移植后护理的进展

Gastro hep advances

Pub Date : 2026-01-01 DOI: 10.1016/j.gastha.2025.100853

Vincent Pedulla , Alyson Kaplan

Alcohol-associated liver disease (ALD) is now the primary indication for liver transplantation (LT) in the United States. While outcomes after LT for ALD are generally excellent, the possibility of post-LT alcohol relapse raises ongoing clinical, ethical, and psychosocial challenges. Relapse is shaped by multiple factors, including young age, comorbid substance use or psychiatric history, lack of social support or engagement, and broader social determinants of health such as education, race, socioeconomic status, and geography. These influences are often difficult to capture through traditional psychosocial assessment alone, and program-level variation in evaluation practices may exacerbate disparities in access to LT. Several relapse prediction tools, including the Sustained Alcohol Use Post-Liver Transplant and Stanford Integrated Psychosocial Assessment for Transplant, have been developed to aid in candidate evaluation. While these tools provide structured approaches, their predictive accuracy remains limited. Biomarkers of alcohol use have emerged as valuable adjuncts to the psychosocial assessment, with phosphatidylethanol showing the greatest promise due to its high sensitivity and specificity and ability to detect alcohol use over a longer period of time. Post-transplant multidisciplinary treatment of alcohol use disorder is also important, including pharmacotherapy and addiction care. Ultimately, optimizing relapse prediction and management requires a framework that accounts not only for individual risk factors but also for structural inequities that shape access to transplantation. Efforts to combine clinical, biological, and social data into unified risk models may provide a more equitable and evidence-based approach to evaluating and supporting patients with ALD before and after LT.

在美国，酒精相关性肝病（ALD）现在是肝移植（LT）的主要适应症。虽然肝移植治疗ALD的结果通常很好，但肝移植后酒精复发的可能性引发了持续的临床、伦理和社会心理挑战。复发受多种因素影响，包括年轻、合并症物质使用或精神病史、缺乏社会支持或参与，以及教育、种族、社会经济地位和地理等更广泛的健康社会决定因素。这些影响通常很难通过传统的社会心理评估来捕获，评估实践中的项目水平差异可能会加剧lt获取的差异。已经开发了几种复发预测工具，包括肝移植后持续酒精使用和斯坦福移植综合社会心理评估，以帮助候选人评估。虽然这些工具提供了结构化的方法，但它们的预测准确性仍然有限。酒精使用的生物标志物已成为社会心理评估的宝贵辅助手段，磷脂酰乙醇因其高灵敏度和特异性以及检测较长时间酒精使用的能力而显示出最大的前景。移植后酒精使用障碍的多学科治疗也很重要，包括药物治疗和成瘾护理。最终，优化复发预测和管理需要一个框架，不仅要考虑个体风险因素，还要考虑影响移植获得的结构性不平等。努力将临床、生物学和社会数据整合到统一的风险模型中，可能会提供更公平和基于证据的方法来评估和支持肝移植前后的ALD患者。

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Gastro hep advances

Pub Date : 2026-01-01

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