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.     

Particulate vs. block bone grafts: Three-dimensional changes in graft volume after reconstruction of the atrophic maxilla,a 2-year radiographic follow-up

BackgroundExtensive alveolar bone resorption in the maxilla limits the possibility of successful placement and osseointegration of endosseous implants for future prosthetic rehabilitation. Autogenous bone from the iliac crest may be used as lateral onlays in the atrophic maxilla, both as block and particulate bone. To our knowledge, there is no three-dimensional 2-year follow-up study measuring the volumetric reduction of the augmented areas comparing particulate and block bone grafts.PurposeThe aim of this study was to conduct a radiographic 2-year follow-up study, using computed tomographic (CT) images in order to evaluate and compare the extent of bone graft resorption in the frontal maxillae augmented by particulate (test) and block bone (control).Material and methodsEleven patients treated with iliac bone grafts and oral implants in the maxilla were followed with CT examinations directly post grafting and after 2 years.ResultThe volumetric changes after 6 months were extensive. Additionally, the changes in particulate bone tended to be larger after 2 years compared to block bone, using this protocol. However, the difference was not statistically significant.ConclusionThe present follow-up study showed that there is radiographically complete integration and embedding of implants installed in grafted bone despite extensive initial graft resorption. There was no significant difference in the amount of volumetric reduction between particulate bone and block bone grafts.     

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.     

UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects and methods: Allele frequencies of SNPs UGT1A4^24Thr, UGT1A4^48Val, UGT2B15^85Tyr, UGT2B15^523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A4^48Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations.

Conclusion: North African populations show a high frequency of carriers of UGT2B15^523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17^del, a variant associated with high concentrations of testosterone and oestradiol.     

Central auditory processing and word discrimination in patients with multiple sclerosis

Many multiple sclerosis (MS) patients with normal pure tone threshold suffer from difficulties in their hearing especially speech perception in background noise, which is possibly because of incompetence of central auditory processing in this group. Three audiologic tests including gap in noise test (GIN), duration pattern sequence test (DPST) and word discrimination score (WDS) were used for comparing a number of aspects of central auditory processing between patients with MS and normal subjects. Approximate threshold and percent of correct answers in GIN test, percent of correct answers in DPST test and monosyllabic discrimination in WDS test were obtained through cross-sectional non-invasive study conducted on 26 subjects with relapsing-remitting multiple sclerosis who had mean age of 28.9 (SD 4.1) years, and 26 18–40-year-old ones with normal hearing and mean age of 27.7 (SD 5.2). Results of this study demonstrate increased approximate threshold and reduction of percent of correct answers obtained from GIN test in patients with multiple sclerosis (Pv = 0.0001). Furthermore in patients with MS, the average of correct answers in DPST was lower than normal subjects and finally performance of MS subjects in WDS test in quiet environment was correlated with GIN threshold (r = ?/624, Pr = /003). Results of the present study showed that patients with MS had defect in aspects of central auditory processing consisting of temporal resolution, auditory pattern and the memory for auditory task and difficulty in discrimination of speech in noisy environment that are related to the involvement of central nervous system.