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Biliary tract cancer, the second most common type of liver cancer, remains a therapeutic challenge due to its late diagnosis and poor prognosis. In recent years, it has become evident that classical chemotherapy might not be the optimal treatment for patients with biliary tract cancer, especially after failure of first-line therapy. Finding new treatment options and strategies to improve the survival of these patients is therefore crucial. With the rise and increasing availability of genetic testing in patients with tumor, novel treatment approaches targeting specific genetic alterations have recently been proposed and have demonstrated their safety and efficacy in numerous clinical trials. In this review, we will first consider chemotherapy options and the new possibility of combining chemotherapy with immune checkpoint inhibitors in first-line treatment. We will then provide an overview of genomic alterations and their potential for targeted therapy especially in second-line therapy. In addition to the most common alterations such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, fibroblast growth factor receptor 2 (FGFR2) fusions, and alterations, we will also discuss less frequently encountered alterations such as BRAF V600E mutation and neurotrophic tyrosine kinase receptor gene (NTRK) fusion. We highlight the importance of molecular profiling in guiding therapeutic decisions and emphasize the need for continued research to optimize and expand targeted treatment strategies for this aggressive malignancy., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Iron deficiency anemia (IDA) is the most common form of anemia worldwide, resulting in a high burden of disease. Accumulating evidence suggests that IDA is associated with the development of gastrointestinal (GI) cancers., Methods: Data from the IDA database (IQVIA) of primary care practices in Germany of adult patients first diagnosed with IDA between January 2005 and December 2021 were retrospectively analyzed and compared with a 1:1 propensity score-adjusted cohort without IDA. Study outcomes were first stomach cancer or colorectal cancer (CRC) diagnosis up to 10 years after the index date as a function of IDA., Results: A total of 122,502 individuals with IDA and 122,502 individuals without IDA were included. The 10-year cumulative incidence of CRC was 1.4% in the IDA patients compared to 0.8% in the cohort without IDA (p < 0.001). Regression analysis revealed a significant association between IDA and subsequent CRC (HR 2.05; 95% CI 1.83-2.30). Stomach cancer was diagnosed in 0.3% of IDA patients compared to 0.2% in the non-IDA cohort during the 10-year follow-up period (p = 0.002). However, this was significant only in the age group > 80 years (HR 2.73; 95% CI 1.60-4.67) and in men (HR 1.90; 95% CI 1.38-2.61)., Conclusion: These findings add to the literature and suggest an association between IDA and GI cancers. The extent to which this association is due to GI bleeding or other pathophysiological processes that may be caused by IDA requires further investigation, particularly experimental studies., (© 2024. The Author(s).)

Purpose: Sleep disorders are among the most common health problems worldwide and are linked to a variety of physical and mental health problems. Recently, there has been increasing evidence of an association between sleep disorders and cancer risk. We aimed to investigate this association specifically for cancers of the gastrointestinal (GI) tract., Methods: Using the DA database (IQVIA), adult patients diagnosed with GI cancer between January 2010 and December 2022 were retrospectively compared to a 1:1 propensity score-matched cohort of patients without cancer. The outcome of the study was the association between sleep disorders and subsequent diagnosis of GI cancer. To determine whether sleep disorders were more common in patients with GI cancer than in patients without GI cancer, logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI)., Results: After matching, 37,161 cases with GI cancer and 37,161 controls without cancer were available for analysis. No association with cancer was found for sleep disorders in the overall history before the index date (OR 1.04; 95% CI 0.96-1.12), but considering sleep disorders documented within 1 year before the index date showed a positive association with GI cancer overall (OR 1.20; 95% CI 1.08-1.34). Stratified analyses by cancer site revealed higher odds of sleep disorders prior to diagnosis of gastric, pancreatic, and colorectal cancer., Conclusion: Our findings suggest that sleep disorders might be indicative of short-term health outcomes, including GI cancer, suggesting a role for sleep disorder screening in the context of cancer prevention efforts., (© 2023. The Author(s).)

Background: Previous studies have found variations in cancer types, tumor progression, and disease outcomes between men and women. However, there is limited knowledge of the effect of sex on gastrointestinal neuroendocrine neoplasms (GI-NENs)., Methods: We identified 1354 patients with GI-NEN from the IQVIA's Oncology Dynamics database. Patients were derived from four European countries (Germany, France, the United Kingdom (UK), Spain). Clinical and tumor related characteristics including patients' age, tumor stage, tumor grading and differentiation, frequency and sites of metastases, as well as co-morbidities were analyzed as a function of patients´ sex., Results: Among the 1354 included patients, 626 were female and 728 were male. The median age was similar between both groups (w: 65.6 years, SD: 12.1 vs. m: 64.7 years; SD: 11.9; p = 0.452). UK was the country with the most patients, however, there was no differences in the sex ratio between the different countries. Among documented co-morbidities, asthma was more often diagnosed in women (7.7% vs. 3.7%), while COPD was more prevalent in men (12.1% vs. 5.8%). The ECOG performance states was comparable between females and males. Of note, the patients´ sex was not associated with tumor origin (e.g., pNET or siNET). Females were overrepresented among G1 tumors (22.4% vs. 16.8%), however, median proliferation rates according to Ki-67 were similar between both groups. In line, no differences in tumor stages was found and rates of metastases as well as the specific sites of metastases were similar between males and females. Finally, no differences in the applied tumor specific treatments between the both sexes became apparent., Conclusion: Females were overrepresented among G1 tumors. No further sex-specific differences became apparent, highlighting that sex-related factors might play a rather subordinate role in the pathophysiology of GI-NENs. Such data may help to better understand the specific epidemiology of GI-NEN., (© 2023. The Author(s).)

Liver diseases represent a significant global health burden, necessitating the development of reliable biomarkers for early detection, prognosis, and therapeutic monitoring. Extracellular vesicles (EVs) have emerged as promising candidates for liver disease biomarkers due to their unique cargo composition, stability, and accessibility in various biological fluids. In this study, we present an optimized workflow for the identification of EVs-based biomarkers in liver disease, encompassing EVs isolation, characterization, cargo analysis, and biomarker validation. Here we show that the levels of microRNAs miR-10a, miR-21, miR-142-3p, miR-150, and miR-223 were different among EVs isolated from patients with nonalcoholic fatty liver disease and autoimmune hepatitis. In addition, IL2, IL8, and interferon-gamma were found to be increased in EVs isolated from patients with cholangiocarcinoma compared with healthy controls. By implementing this optimized workflow, researchers and clinicians can improve the identification and utilization of EVs-based biomarkers, ultimately enhancing liver disease diagnosis, prognosis, and personalized treatment strategies.

Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies.