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.     

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6–20.7) and 32.3 (95% CI 27.3–38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58–5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip.