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.     

Anästhesiologische Risikoevaluation und rechtssichere Aufklärung per Telemedizin – Sind wir bereit für einen Paradigmenwechsel?

Die Anaesthesiologie - In Deutschland werden pro Jahr 17 Millionen Narkosen und damit auch ungefähr so viele Narkosevorgespräche durchgeführt. Bis dato finden diese praktisch...     

Der Notfall – unendliche Welten?

Die Anaesthesiologie - Simulationstraining ist für die Notfallmedizin unverzichtbar, insbesondere in Hinsicht auf eine verbesserte Patientensicherheit. Methoden und Technologien umfassen ein...     

Praxis der perioperativen Prävention von Phantomschmerz: eine deutschlandweite Umfrage

Die Anaesthesiologie - Phantomschmerzen haben eine hohe Prävalenz nach Majoramputationen und sind mit einer zusätzlichen Einschränkung der Lebensqualität verbunden....     

A Review of Aerosol Generation Mitigation in International Dental Guidance

IntroductionThe coronavirus disease 2019 (COVID-19) led to the worldwide closure of dental practices or reduction of dental services. By the end of April 2020, governments and professional organisations were publishing recommendations or guidance for the reopening/restructuring of dental services. The aim of this study was to assess how dental aerosol-generating procedures (AGPs) were defined in international dental guidelines, what mitigation processes were advised, and whether they were linked to COVID-19 epidemiology.MethodsElectronic searches of a broad range of databases, along with grey literature searches, without language restriction were conducted up to 13 July 2020. Recommendations for the use of face masks and fallow times with patients without COVID-19 were assessed against the deaths per 1 million population in the included countries and country income level using Pearson Chi-squared statistics.ResultsSixty-three guidance documents were included. Most (98%) indicated that AGPs can be performed with patients without COVID-19 with caveats, including advice to restrict AGPs where possible, with 21% only recommending AGPs for dental emergencies. Face masks were recommended by most documents (94%), with 91% also specifying the use of goggles or face shields. Fallow periods for patients without COVID-19 were mentioned in 48% of documents, ranging from 2 to 180 minutes. There were no significant differences in recommendations for face masks or fallow time in patients without COVID-19 by country death rate (P = .463 and P = .901) or World Bank status (P = .504 and P = .835). Most documents recommended procedural or environmental mitigations such as preprocedural mouthwash (82%) and general ventilation (52%). Few documents provided underpinning evidence for their recommendations.ConclusionsWhile the amount of high-quality direct evidence related to dentistry and COVID-19 remains limited, it is important to be explicit about the considered judgements for recommendations as well as generate new evidence to face this challenge.     

WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.