Intrahepatic cholangiocarcinoma: current management and emerging therapies

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify ‘target-able’ molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients.

Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies.

Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.     

Psychological and Sociocultural Adaptation: Acculturation,Depressive Symptoms,and Life Satisfaction Among Older Iranian Immigrants in Canada

Informed by Ward’s (1996) theory of psychological and sociocultural adaptation, this study identified links between acculturation and the mental health of older Iranian immigrants living in Canada (N = 103). According to Ward and colleagues, both psychological and sociocultural adaptation change at different rates and extend into later life. For this study, participants 50+ years of age and born in Iran completed questionnaires measuring life satisfaction, depressive symptoms, acculturation, and demographic and sociocultural variables (e.g., pre- and post-immigration occupational status). We collected study data anonymously in Persian to obtain responses from long-term residents of Canada as well as more recent immigrants who may not read or write English. We examined both life satisfaction and (the absence of) depressive symptoms as distinct forms of psychological adaptation; these emerged as independent predictors of acculturation. Contrary to theory, acculturation appears to predict life satisfaction, not vice versa; moreover, there seems to be no direct link between depressive symptoms and acculturation. Our findings suggest that integration within Canadian society is associated with higher life satisfaction. In contrast, sociocultural factors are indirectly associated with life satisfaction (except age) and acculturation (except ethnic diversity of social interactions). Involuntary migrants reported higher levels of depression, whereas loss of occupational status is associated with reduced life satisfaction. Implications for future research and health policy are discussed.     

Disturbance of zinc and glucose homeostasis by methyl tert-butyl ether (MTBE); evidence for type 2 diabetes

1.?The prevalence of diabetes and the other metabolic disorders has noticeably increased worldwide. A causal link between increasing risk of type 2 diabetes and exposure to environmental pollutants has been reported.

2.?We hypothesized that exposure to methyl tert-butyl ether (MTBE), an oxygenate additive to gasoline would hinder zinc and glucose homeostasis in rats.

3.?Male Sprague–Dawley rats received MTBE in drinking water for 90 days. At the end of the treatment, pancreas and blood samples were collected for biochemical and molecular examinations. Expression of four candidate genes, including Insulin1, Insulin2, MT1A, SLC30A8 by Real-Time Quantitative PCR (Q-PCR) as well as biochemical parameters, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), copper (Cu²⁺) and calcium (Ca²⁺) levels as well as High-sensitive C-reactive protein were assessed as endpoints.

4.?This study suggested that MTBE exposure can be associated with disruption in zinc homeostasis and glucose tolerance.