Search

A Consensus Conference of clinicians, researchers, public health specialists and users was convened in Italy to review efficacy, effectiveness, treatment appropriateness and access to care for anxiety and depression, and to consider the role of psychological therapies. Expert opinion was sought concerning identification of people requiring psychological therapies according to levels of symptom severity matched to corresponding levels of treatment intensity, suitability of psychological therapies for subclinical anxiety or depression, definition of a minimum level of information on evidence-based psychotherapies to be provided by university medical and psychology courses, initiatives to raise awareness among potential users and decision makers on the role and effectiveness of psychological therapies in healthcare. The expert jury concluded that a number of psychological therapy models endorsed by most authoritative guidelines are supported by research showing their effectiveness at least equal to the drugs used in common mental disorders (CMDs). Such therapies are under-represented in the Italian public health system, leading many people to resort to the private sector, resulting in unacceptable wealth discrimination. The difficulty of accessing psychological treatments often entails the use of drug therapies in cases where they are not indicated. Starting from these assumptions, the experts recommended the promotion of better and timely recognition of anxiety and depressive disorders and their classification in terms of symptom intensity and functional impairment, differentiating subthreshold mood swings from clinical forms, to foster outcome studies of psychotherapies in CMDs in Italy, to introduce a stepped care model structured according to levels of intensity of treatment, based on wellbeing support strategies in nonmedical contexts for subthreshold situations, self-help, support and psychoeducation as frontline interventions in mild clinical forms, evidence-based psychotherapies in moderate and severe forms, with the option of combining psychological treatment and appropriate drug therapy in the most severe cases.

This editorial describes the clinical trials related to antidiabetic drugs, most of them following an "add-on" design of where the new drug is added to metformin and the comparative arm is metformin plus placebo. Many drugs are already approved for therapy following this design; the authors believe that it is unethical to continue this trend because it makes it impossible to stratify the many antidiabetic drugs according to their efficacy and toxicity.

Introduction Prevalence of cancer patients is dramatically increasing. We aimed at quantifying the oncology workload generated by each new cancer patient in the two years following first consultation. Methods In this record-based retrospective study, we retrieved data of all newly diagnosed patients treated at the Oncology Department of Udine Academic Hospital between 01.01.2012 and 31.12.2017. We calculated mean number and standard deviation of the activity type generated by each new cancer patient during the following 2 years. Results Seven thousand four hundred fifty-two cancer patients generated a total of 85,338 clinical episodes. The two-years mean number of oncology episodes generated was 11.31 (i.e., for every 1,000 new cancer patients, 11,310 oncology activities are generated overall in the following two-year lapse). Patients with advanced disease generated the highest workload (24.3; SD 18.8) with a statistically significant difference compared to adjuvant and follow-up patients (p p p Conclusion This is the first study reporting on the mean oncology workload generated during the 2 years following first consultation. Workload is the highest for patient with advanced disease, especially in the first months and in patients in active treatment. A detailed analysis of workloads in oncology is feasible and could be crucial for planning a sustainable framework for cancer care in the next future.

IntroductionUp to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts’ involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.Methods and analysisThis is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.Ethics and disseminationThis trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.Trial registration numberNCT03914820.

Introduction At the time of diagnosis, 15–20% of gastric carcinomas are in stage T4 or T4b. Furthermore, 5–20% of patients undergoing potentially curative surgery suffer from synchronous or metachronous peritoneal metastases. To date, neither surgery nor systemic chemotherapy successfully controls peritoneal dissemination, offering a limited impact on survival. Peritoneal metastases are in fact responsible for death in around 60% of gastric cancer patients. Several Eastern studies in the past have focused on hyperthermic intraperitoneal chemotherapy (HIPEC) as a prophylactic measure in patients with serosal extension, nodal involvement, and positive peritoneal fluid cytology. Therefore, a new multimodal therapeutic strategy based on aggressive surgery plus new locoregional treatment may prolong survival in this particular clinical scenario. Methods This study compares the efficacy of prophylactic surgery (radical gastric resection, appendectomy, resection of the round ligament of the liver, and bilateral adnexectomy) plus hybrid CO2 HIPEC system versus standard surgery in patients with T3-T4 N0-N + gastric adenocarcinoma. Patients will be randomly assigned (1:1 ratio) to the experimental arm or standard surgery. The primary endpoint is to establish the difference in disease-free survival between the groups. The secondary objective is to compare the safety and tolerability of prophylactic surgery plus HIPEC CO2 versus standard surgery. Discussion Considering the poor prognosis of patients with peritoneal dissemination from gastric cancer, a prophylactic strategy to prevent peritoneal metastases may be beneficial. In patients with gastric cancer at high risk of peritoneal carcinomatosis, we propose aggressive surgical treatment with radical gastrectomy, removal of organs at risk of harbouring tumour cells, and HIPEC. Trial registration ClinicalTrials.gov NCT03917173. Registered on 16 April 2019. Protocol version: v1, March 27, 2019. Protocol number: IRFMN-GCC-7813. EudraCT number: 2019–001478-27.

Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship between CDH1 mRNA expression and HER2-positivity in mGC using a multiplexed gene expression profile in two series of gastric cancer (GC): Series 1 (n = 38): HER2+ and HER2- mGC; Series 2 (n = 36) HER2- GC with and without metastasis. To confirm the results, the same expression profiles were analyzed in 354 GC from The Cancer Genome Atlas (TCGA) dataset. The difference in gene expression connected HER2 overexpression with canonical wingless-type (Wnt)/β-catenin pathway and immunohistochemical (IHC) expression loss of E-cadherin (E-CAD). CDH1 mRNA expression was simultaneously associated with the rs16260-A variant and an increase in E-CAD expression. Differences in retinoic acid receptor alfa (RARA), RPL19 (coding for the 60S ribosomal L19 protein), catenin delta 1 (CTNND1), and epidermal growth factor (EGF) mRNA levels—all included in the Wnt/β-catenin pathway—were found associated with overall survival (OS). RARA, CTNND1, and EGF resulted in independent OS prognostic factors. EGF was confirmed as an independent factor along with TNM stage in HER2-overpressed mGC from TCGA collection. Our study highlighted factors involved in the WNT/β-catenin pathway that interconnected E-CAD with HER2 overexpression and patient survival.