Systemic Treatment for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a diverse group of epithelial cancers that affect the biliary tree. The incidence of CCA is low in Western countries but significantly higher in endemic regions such as China and Thailand. Various risk factors contribute to the development of CCA. Recent studies have revealed molecular alterations in biliary tract cancers, providing insights into cholangiocarcinogenesis and potential targeted therapies. Surgical resection is the primary curative treatment for CCA. Adjuvant chemotherapy has been extensively studied, and some regimens have proven to be beneficial. Neoadjuvant chemotherapy has shown potential benefits in select cases, but its role remains controversial. In advanced stages, chemotherapy is the standard of care, and molecular profiling has identified potential targets such as FGFR, IDH1, HER2, and other tumor-agnostic therapies. Immunotherapy has demonstrated limited benefit in advanced CCA. This chapter provides an overview of the current evidence and ongoing research evaluating various chemotherapy regimens, targeted therapies, and immunotherapies across different stages of CCA.

Risk factors of left ventricular hypertrophy in obstructive sleep apnea.

Obstructive sleep apnea (OSA) and left ventricular hypertrophy (LVH) are both related to major cardiovascular diseases. Previous studies have indicated that, compared with non-OSA, OSA is related to LVH with an odds ratio (OR) of 1.70 (95% CI: 1.44-2.00), particularly in patients with coronary artery disease. Meta-analysis has revealed that the severity of OSA is significantly associated with left ventricular mass compared with non-OSA controls. There is, however, limited data on the risk factors of LVH in patients with OSA. The present study aimed to assess the prevalence and clinical factors that are predictive of LVH in patients with OSA. A retrospective analysis of adult patients diagnosed with OSA who had undergone echocardiography was performed. LVH defined by echocardiography indicated an enlarged LV mass index. Clinical factors predictive of LVH were assessed using multivariate logistic regression analyses. An unadjusted OR and an adjusted OR with 95% confidence intervals (CI) were determined. During the study period, 130 patients met the study criteria, with an LVH prevalence of 27.69% (36 patients). The final predictive model of LVH comprised six factors: Age, sex, unrefreshed sleep, body mass index, systolic blood pressure and apnea-hypopnea index. Only age was independently associated with LVH, with an adjusted OR of 1.048 (95% CI: 1.002-1.096). The prevalence rate of LVH in patients with OSA was 27.69%. Older age was independently related to LVH in patients with OSA.

Repurposing Metformin for Cancer Treatment: A Great Challenge of a Promising Drug.

The safety windows and toxicity of clinically available known drugs allow drug repurposing to be a popular treatment strategy for several diseases, including cancers. Several common drugs, e.g., metformin, statin, and aspirin are on clinical trials for repurposing in oncology treatment. Most of repurposed drugs, however, cannot be used as single agents and some do not exert any clinically significant effects. The limitations and possible biases from observational studies and preclinical models to repurpose these drugs are debatable. In this article, the limitations and probability of using metformin, one of the most repurposed drugs for cancer treatment and in oncological practice, are discussed.

Association of Diabetes Mellitus and Cholangiocarcinoma: Update of Evidence and the Effects of Antidiabetic Medication.

Diabetes mellitus (DM) is a risk factor for cancer in many organs and associated with an increased risk of cholangiocarcinoma (CCA). The molecular linkage between these diseases has been demonstrated in preclinical studies, which have highlighted the role of hyperinsulinemia and hyperglycemia in the carcinogenesis and progression of CCA. Recent studies on the emerging role of antidiabetic medication in the development and progression of CCA showed a subclass of antidiabetic drug with a therapeutic effect on CCA. Although associations between CCA, insulin analogues and sulfonylureas are unclear, incretin-based therapy is likely associated with an increased risk for CCA, and may lead to CCA progression, as demonstrated by in vitro and in vivo experiments. In contrast, biguanides, especially metformin, exert an opposite effect, associated with a reduced risk of CCA and inhibited in vitro and in vivo CCA progression. The association between incretin-based therapy and the risk of CCA needs further clarification, as metformin is being studied in an ongoing clinical trial. Understanding the association between DM and CCA is critical for preventing the development of CCA in patients with DM, and for establishing the appropriateness of antidiabetic medication to treat CCA. Determining how metformin affects CCA can lead to repurposing this safe and well-known drug for improving CCA treatment, regardless of the diabetes status of patients.