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.     

低温等离子腺样体切除联合双侧扁桃体方案治疗儿童鼾症的疗效及其影响因素研究

目的 探讨低温等离子腺样体切除联合双侧扁桃体方案治疗儿童鼾症的疗效及其影响因素研究。 方法 选取鼾症患儿110例作为研究对象，按照随机数字表法分为对照组与观察组，各55例。观察治愈率及总有效率，对比术前、术后1个月、6个月的免疫球蛋白A(immunoglobulin A，IgA)、免疫球蛋白G(immunoglobulin G，IgG)、免疫球蛋白M(immunoglobulin M，IgM)。评估术前、术后7 d的呼吸暂停低通气指数（apnea hypopnea index，AHI）、夜间最低氧饱和度［minimum blood oxygen saturation，LSa(O2）］及儿童睡眠问卷(pediatric sleep questionnaire,PSQ)评分。 结果 观察组的总有效率高于对照组，且治愈率高于对照组（P＜0.05）。观察组手术时间、术中出血量、术后疼痛时间及症状缓解时间均低于对照组（P＜0.05）。2组IgA、IgG、IgM均随着时间增加，术后1个月、6个月，观察组的IgA、IgG、IgM高于对照组（P＜0.05）。2组IgA、IgG、IgM在组间，时点间，组间时点间交互作用比较差异有统计学意义（P＜0.05）。简单效应LSD-t成对比较显示，术前2组IgA、IgG、IgM、AHI、LSa(O2）及PSQ评分比较，差异无统计学意义（P＞0.05）；术后1个月、6个月，观察组的IgA、IgG、IgM高于对照组（P＜0.05）。术后7 d，观察组的AHI低于对照组，而LSa(O2）、PSQ评分高于对照组（P＜0.05）。治愈/显效组与有效/无效组在性别、年龄、病程、体重、术前IgA、术前IgG、术前IgM、术前AHI、术前LSa(O2）、术前PSQ评分比较中，差异无统计学意义（P＞0.05）；而在手术方法比较中差异有统计学意义（P＜0.05）。logistic回归分析显示，动力切割系统切除腺样体联合常规剥离双侧扁桃体手术是影响儿童鼾症治疗效果的独立危险因素（P＜0.05）。 结论 低温等离子腺样体切除联合双侧扁桃体切除治疗小儿鼾症效果显著，不仅对免疫功能影响小，并且能改善患者通气功能。     

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.