Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Characteristics Associated with Reliability in Reporting of Contraceptive Use: Assessing the Reliability of the Contraceptive Calendar in Seven Countries

Although the reproductive calendar is the primary tool for measuring contraceptive dynamics in low-income settings, the reliability of calendar data has seldom been evaluated, primarily due to the lack of longitudinal panel data. In this research, we evaluated the reproductive calendar using data from the Performance Monitoring for Action Project. We used population-based longitudinal data from nine settings in seven countries: Burkina Faso, Nigeria (Kano and Lagos States), Democratic Republic of Congo (Kinshasa and Kongo Central Provinces), Kenya, Uganda, Cote d'Ivoire, and India. To evaluate reliability, we compared the baseline cross-sectional report of contraceptive use (overall and by contraceptive method), nonuse, or pregnancy with the retrospective reproductive calendar entry for the corresponding month, measured at follow-up. We use multivariable regressions to identify characteristics associated with reliability or reporting. Overall, we find that the reliability of the calendar is in the “moderate/substantial” range for nearly all geographies and tests (Kappa statistics between 0.58 and 0.81). Measures of the complexity of the calendar (number of contraceptive use episodes, using the long-acting method at baseline) are associated with reliability. We also find that women who were using contraception without their partners/husband's knowledge (i.e., covertly) were less likely to report reliably in several countries.     

Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.