The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

[Prevalence of burnout syndrome and its associated factors in Primary Care staff]. / Prevalencia del síndrome del burnout y factores asociados a dicho síndrome en los profesionales sanitarios de Atención Primaria.

INTRODUCTION: Burnout syndrome is an emerging disease among health professionals. The aim of this study is to determine the prevalence of occupational burnout among Primary Care staff, as well as to determine the differences in prevalence between family doctors, paediatricians, nurses, administrative-officers, and social-workers, and to evaluate the different related factors. MATERIALS AND METHODS: A cross-sectional, descriptive study was conducted on 178 professionals from 5 different occupational groups in 54 Primary Care centres in Navarre from September to December 2010. An anonymous, self-administered questionnaire that included: the Maslach Burnout Inventory and a questionnaire on socio-demographic and work-related factors. RESULTS: Burnout was detected in 39.3% of staff. Those with higher levels are administrative-officers and family doctors, with an OR compared to nurses of 4.58 and 5.37, respectively in the dimension of emotional exhaustion, 4.98 and 2.87 in depersonalization, and 8.37 for administrative-officers in personal accomplishment. An association was found between burnout and the following factors: to be a male (for the dimensions of emotional exhaustion and depersonalization, 25.5 and 31.9%, respectively), to be employed in an urban area (for emotional exhaustion and depersonalization, 20 and 27.8%, respectively), use of psychiatric medication (for emotional exhaustion, 30%), size of patient-quota (for depersonalization, with an average of 1,565 patients), and welfare pressure (for emotional exhaustion and depersonalization, averages of 170.35 and 153.54 patients/week, respectively). CONCLUSIONS: About one-third of Primary Care professionals have a high level of burnout, which is mainly associated with the working area, the size of the quota, and professional group, with higher prevalence in administrative-officers and family doctors.

Role of the new azoles in the treatment of fungal osteoarticular infections.

OBJECTIVES: To analyze the usefulness of the new azoles for the treatment of fungal osteoarticular infections, and to report three cases of fungal knee arthritis treated with fluconazole in our unit. METHODS: The medical literature was reviewed for all cases of osteoarticular infection caused by fungi and treated with fluconazole or itraconazole registered in the MedLine Silver Platter database from 1972 to 1997. RESULTS: The total number of patients included in this review was 56; 19 were treated with fluconazole and 37 with itraconazole. The most frequent causative agents implicated were fungi of the genuses Candida and Aspergillus. There were eight therapeutic failures, and there were no statistically different findings among the patients in terms of their health status. Adverse effects were unusual. CONCLUSIONS: Controlled studies are necessary to establish the true role of the new azole drugs in the treatment of fungal osteoarticular infections, but they seem to be a promising therapeutic option.