Prostate cancer incidence and mortality in Europe and implications for screening activities: population based study.

OBJECTIVE: To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives. DESIGN: Population based study. SETTING: 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer's Global Cancer Observatory, and mortality data from the World Health Organization. POPULATION: Men aged 35-84 years from 26 eligible countries. RESULTS: Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in several countries. Mortality rates during 1980-2020 were much lower and less variable than incidence rates, with steady declines in most countries and lesser temporal differences between countries. Overall, the up to 20-fold variation in prostate cancer incidence contrasts with a corresponding fivefold variation in mortality. Also, the inverse U-shape of the age specific curves for incidence contrasted with the mortality pattern, which increased progressively with age. The difference between the highest and lowest incidence rates across countries ranged from 89.6 per 100 000 men in 1985 to 385.8 per 100 000 men in 2007, while mortality rates across countries ranged from 23.7 per 100 000 men in 1983 to 35.6 per 100 000 men in 2006. CONCLUSIONS: The epidemiological features of prostate cancer presented here are indicative of overdiagnosis varying over time and across populations. Although the results are ecological in nature and must be interpreted with caution, they do support previous recommendations that any future implementation of prostate cancer screening must be carefully designed with an emphasis on minimising the harms of overdiagnosis.

Upcoming Italian clinical practice guidelines on endoscopic bariatric treatment of overweight and obesity: design and methodological aspects.

Obesity/overweight and its complications are a growing problem in many countries. Italian Society of Bariatric and Metabolic Surgery for Obesity (Società Italiana di Chirurgia dell'Obesità e delle Malattie Metaboliche-SICOB) decided to develop the first Italian guidelines for the endoscopic bariatric treatment of obesity. The creation of SICOB Guidelines is based on an extended work made by a panel of 44 members and a coordinator. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide the aims, reference population, and target health professionals. Clinical questions have been created using the PICO (patient, intervention, comparison, outcome) conceptual framework. We will perform systematic reviews, formal meta-analyses, and network meta-analyses for each PICO and critical outcomes aimed at assessing and rating the efficacy and safety of endoscopic bariatric procedures in comparison with either no interventions, lifestyle interventions, or approved anti-obesity treatments in trials with a follow-up of at least 52 weeks. For PICO on temporary endoscopic bariatric treatments, we will also consider RCT with a minimum duration of 6 months. The panel proposed 8 questions, organized into four domains: A. Indication for endoscopic bariatric surgery; B. Revisional surgery; C. Temporary gastric and duodenal-jejunal procedures; D. Endoscopic diagnosis/treatment of bariatric and metabolic surgery complications. These guidelines will apply to patients aged ≥ 14 years) with body mass index (BMI) ≥ 27 kg/m2 and requiring endoscopic bariatric surgery or endoscopic diagnostic and/or therapeutic procedures. The areas covered by the clinical questions included indications of endoscopic bariatric surgery, types of surgery, revisional surgery, and management of bariatric and metabolic surgery complications.

Cost-Effectiveness of Treatment Optimisation with Biomarkers for Immunotherapy in Solid Tumours: A Systematic Review.

This study investigated the health economic evaluations of predictive biomarker testing in solid tumours treated with immune checkpoint inhibitors (ICIs). Searching PubMed, EMBASE, and Web of Science from June 2010 to February 2022, 58 relevant articles were reviewed out of the 730 screened. The focus was predominantly on non-small cell lung cancer (NSCLC) (65%) and other solid tumours (40%). Among the NSCLC studies, 21 out of 35 demonstrated cost-effectiveness, notably for pembrolizumab as first-line treatment when preceded by PD-L1 assessment, cost-effective at a threshold of $100,000/QALY compared to the standard of care. However, for bladder, cervical, and triple-negative breast cancers (TNBCs), no economic evaluations met the affordability threshold of $100,000/QALY. Overall, the review highlights a certain degree of uncertainty about the cost-effectiveness of ICI. In particular, we found PD-L1 expression associated with ICI treatment to be a cost-effective strategy, particularly in NSCLC, urothelial, and renal cell carcinoma. The findings suggest the potential value of predictive biomarker testing, specifically with pembrolizumab in NSCLC, while indicating challenges in achieving cost-effectiveness for certain other solid tumours.

Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study.

Background: Reducing socioeconomic inequalities in cancer is a priority for the public health agenda. A systematic assessment and benchmarking of socioeconomic inequalities in cancer across many countries and over time in Europe is not yet available. Methods: Census-linked, whole-of-population cancer-specific mortality data by socioeconomic position, as measured by education level, and sex were collected, harmonized, analysed, and compared across 18 countries during 1990-2015, in adults aged 40-79. We computed absolute and relative educational inequalities; temporal trends using estimated-annual-percentage-changes; the share of cancer mortality linked to educational inequalities. Findings: Everywhere in Europe, lower-educated individuals have higher mortality rates for nearly all cancer-types relative to their more highly-educated counterparts, particularly for tobacco/infection-related cancers [relative risk of lung cancer mortality for lower- versus higher-educated = 2.4 (95% confidence intervals: 2.1-2.8) among men; = 1.8 (95% confidence intervals: 1.5-2.1) among women]. However, the magnitude of inequalities varies greatly by country and over time, predominantly due to differences in cancer mortality among lower-educated groups, as for many cancer-types higher-educated have more similar (and lower) rates, irrespective of the country. Inequalities were generally greater in Baltic/Central/East-Europe and smaller in South-Europe, although among women large and rising inequalities were found in North-Europe (relative risk of all cancer mortality for lower- versus higher-educated ≥1.4 in Denmark, Norway, Sweden, Finland and the England/Wales). Among men, rate differences (per 100,000 person-years) in total-cancer mortality for lower-vs-higher-educated groups ranged from 110 (Sweden) to 559 (Czech Republic); among women from approximately null (Slovenia, Italy, Spain) to 176 (Denmark). Lung cancer was the largest contributor to inequalities in total-cancer mortality (between-country range: men, 29-61%; women, 10-56%). 32% of cancer deaths in men and 16% in women (but up to 46% and 24%, respectively in Baltic/Central/East-Europe) were associated with educational inequalities. Interpretation: Cancer mortality in Europe is largely driven by levels and trends of cancer mortality rates in lower-education groups. Even Nordic-countries, with a long-established tradition of equitable welfare and social justice policies, witness increases in cancer inequalities among women. These results call for a systematic measurement, monitoring and action upon the remarkable socioeconomic inequalities in cancer existing in Europe. Funding: This study was done as part of the LIFEPATH project, which has received financial support from the European Commission (Horizon 2020 grant number 633666), and the DEMETRIQ project, which received support from the European Commission (grant numbers FP7-CP-FP and 278511). SV and WN were supported by the French Institut National du Cancer (INCa) (Grant number 2018-116). PM was supported by the Academy of Finland (#308247, # 345219) and the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No 101019329). The work by Mall Leinsalu was supported by the Estonian Research Council (grant PRG722).

Initial 50 consecutive full-robotic pancreatoduodenectomies without conversion by a single surgeon: a learning curve analysis from a tertiary referral high-volume center.

BACKGROUND: Several studies report on a learning curve for robotic pancreatoduodenectomy (R-PD) ranging between 20 and 80 operations, with conversion rates varying between 1.1 and 35%. However, as these publications mostly refer to initial robotic experiences and do not take into account the previous surgical background in pancreatic surgery (PS) and in robotic-assisted surgery (RAS), the center's volume, as well as the platform used, we aimed to perform a surgical outcomes analysis with a particular view to these aspects. METHODS: Intraoperative and perioperative outcomes of the first 50 consecutive R-PD performed with the da Vinci Xi by the same surgeon, within a tertiary referral high-volume center, between January 2018 and March 2022, were analyzed. The surgeon was previously experienced in both PS and RAS. Shewhart control chart and cumulative sum (CUSUM) analysis were used to evaluate the learning curve of R-PD. RESULTS: All the operations were performed with a full-robotic technique, without any conversion to open surgery. Twenty of 50 patients (40%) had a BMI ≥ 25 kg/m2, while 24/50 (48%) had undergone previous abdominal surgery. Mean console time was 276.30 ± 31.16 min. The median post-operative length of hospital stay was 10 days, while 20/50 (40%) patients were discharged within post-operative day 8. Six patients (12%) had major complications (Clavien-Dindo grade 3 or above). There was no 30-day mortality. Shewhart control chart and CUSUM analysis did not show a significant learning curve during the study period. CONCLUSIONS: An extensive prior experience in both PS and RAS, within a tertiary referral high-volume center with availability of the da Vinci Xi platform, can significantly flatten the learning curve and, therefore, enable safe performance of challenging operations, i.e., pancreatoduodenectomies with a minimally invasive approach, with very low risk of conversion to open surgery, even in the first 50 operations.

Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative.

BACKGROUND: Tracking progress and providing timely evidence is a fundamental step forward for countries to remain aligned with the targets set by WHO to eliminate cervical cancer as a public health problem (ie, to reduce the incidence of the disease below a threshold of 4 cases per 100 000 women-years). We aimed to assess the extent of global inequalities in cervical cancer incidence and mortality, based on The Global Cancer Observatory (GLOBOCAN) 2020 estimates, including geographical and socioeconomic development, and temporal aspects. METHODS: For this analysis, we used the GLOBOCAN 2020 database to estimate the age-specific and age-standardised incidence and mortality rates of cervical cancer per 100 000 women-years for 185 countries or territories aggregated across the 20 UN-defined world regions, and by four-tier levels of the Human Development Index (HDI). Time trends (1988-2017) in incidence were extracted from the Cancer Incidence in Five Continents (CI5) plus database. Mortality estimates were obtained using the most recent national vital registration data from WHO. FINDINGS: Globally in 2020, there were an estimated 604 127 cervical cancer cases and 341 831 deaths, with a corresponding age-standardised incidence of 13·3 cases per 100 000 women-years (95% CI 13·3-13·3) and mortality rate of 7·2 deaths per 100 000 women-years (95% CI 7·2-7·3). Cervical cancer incidence ranged from 2·2 (1·9-2·4) in Iraq to 84·6 (74·8-94·3) in Eswatini. Mortality rates ranged from 1·0 (0·8-1·2) in Switzerland to 55·7 (47·7-63·7) in Eswatini. Age-standardised incidence was highest in Malawi (67·9 [95% CI 65·7 -70·1]) and Zambia (65·5 [63·0-67·9]) in Africa, Bolivia (36·6 [35·0-38·2]) and Paraguay (34·1 [32·1-36·1]) in Latin America, Maldives (24·5 [17·0-32·0]) and Indonesia (24·4 [24·2-24·7]) in Asia, and Fiji (29·8 [24·7-35·0]) and Papua New Guinea (29·2 [27·3-31·0]) in Melanesia. A clear socioeconomic gradient exists in cervical cancer, with decreasing rates as HDI increased. Incidence was three times higher in countries with low HDI than countries with very high HDI, whereas mortality rates were six times higher in low HDI countries versus very high HDI countries. In 2020 estimates, a general decline in incidence was observed in most countries of the world with representative trend data, with incidence becoming stable at relatively low levels around 2005 in several high-income countries. By contrast, in the same period incidence increased in some countries in eastern Africa and eastern Europe. We observed different patterns of age-specific incidence between countries with well developed population-based screening and treatment services (eg, Sweden, Australia, and the UK) and countries with insufficient and opportunistic services (eg, Colombia, India, and Uganda). INTERPRETATION: The burden of cervical cancer remains high in many parts of the world, and in most countries, the incidence and mortality of the disease remain much higher than the threshold set by the WHO initiative on cervical cancer elimination. We identified substantial geographical and socioeconomic inequalities in cervical cancer globally, with a clear gradient of increasing rates for countries with lower levels of human development. Our study provides timely evidence and impetus for future strategies that prioritise and accelerate progress towards the WHO elimination targets and, in so doing, address the marked variations in the global cervical cancer landscape today. FUNDING: French Institut National du Cancer, Horizon 2020 Framework Programme for Research and Innovation of the European Commission; and EU4Health Programme.

The Current Burden of Oropharyngeal Cancer: A Global Assessment Based on GLOBOCAN 2020.

BACKGROUND: Oropharyngeal cancer (OPC) is a complex disease whose etiologies, either related to risk factors such as smoking or alcohol, or linked to HPV infection, are believed to be responsible for wide gender and geographical variability. This study depicts the current burden of OPC worldwide. METHODS: Estimated OPC new cases, deaths, age-standardized rates (ASR) for both incidence and mortality in 2020 were obtained from the GLOBOCAN database for each country and across 20 UN-defined world regions by sex. The incidence-to-mortality ratio (IMR) was also estimated from ASR. RESULTS: Worldwide, 98,400 new cases and 48,100 OPC deaths were estimated in 2020, with ASR of 1.1 and 0.51 per 100,000 for incidence and mortality, respectively. ASR for both incidence and mortality were approximately four times higher in men and varied greatly across geographical regions and countries within the same region. Higher incidence was estimated in Europe, North-America, Australia, and New Zealand. Mortality was the highest in Central-East Europe, Western Europe, Melanesia, South-Central Asia, and the Caribbean. South-Central Asia, most African areas, and Central America exhibited the lowest IMR values, whereas North-America, Australia, New Zealand, and North-Europe had the highest. CONCLUSIONS: The marked geographical and gender variability in OPC incidence and mortality is likely to reflect the distribution of risk factors and the diverse prevalence of HPV-negative and HPV-positive cases. IMPACT: Findings are likely to drive future research, support the development of targeted strategies to counteract disease burden, establish priorities for prevention and treatment programs, and address inequality in access to services.

Minimally invasive distal pancreatectomy: a case-matched cost-analysis between robot-assisted surgery and direct manual laparoscopy.

BACKGROUND: Few studies have reported a structured cost analysis of robotic distal pancreatectomy (RDP), and none have compared the relative costs between the robotic-assisted surgery (RAS) and the direct manual laparoscopy (DML) in this setting. The aim of the present study is to address this issue by comparing surgical outcomes and costs of RDP and laparoscopic distal pancreatectomies (LDP). METHODS: Eighty-eight RDP and 47 LDP performed between January 2008 and January 2020 were retrospectively analyzed. Three comparable groups of 35 patients each (Si-RDP-group, Xi-RDP group, LDP-group) were obtained matching 1:1 the RDP-groups with the LDP-group. Overall costs, including overall variable costs (OVC) and fixed costs were compared using generalized linear regression model adjusting for covariates. RESULTS: The conversion rate was significantly lower in the Si-RDP-group and Xi-RDP-group: 2.9% and 0%, respectively, versus 14.3% in the LDP-group (p = 0.045). Although not statistically significant, the mean operative time was lower in Xi-RDP-group: 226 min versus 262 min for Si-RDP-group and 247 min for LDP-group. The overall post-operative complications rate and the length of hospital stay (LOS) were not significantly different between the three groups. In LDP-group, the LOS of converted cases was significantly longer: 15.6 versus 9.8 days (p = 0.039). Overall costs of LDP-group were significantly lower than RDP-groups, (p < 0.001). At multivariate analysis OVC resulted no longer statistically significantly different between LDP-group and Xi-RDP-group (p = 0.099), and between LDP-group and the RDP-groups when the spleen preservation was indicated (p = 0.115 and p = 0.261 for Si-RDP-group and Xi-RDP-group, respectively). CONCLUSIONS: RAS is more expensive than DML for DP because of higher acquisition and maintenance costs. The flattening of these differences considering only the variable costs, in a high-volume multidisciplinary center for RAS, suggests a possible optimization of the costs in this setting. RAS might be particularly indicated for minimally invasive DP when the spleen preservation is scheduled.

Robot-assisted pancreatoduodenectomy with the da Vinci Xi: can the costs of advanced technology be offset by clinical advantages? A case-matched cost analysis versus open approach.

BACKGROUND: Robot-assisted pancreatoduodenectomy (RPD) has shown some advantages over open pancreatoduodenectomy (OPD) but few studies have reported a cost analysis between the two techniques. We conducted a structured cost-analysis comparing pancreatoduodenectomy performed with the use of the da Vinci Xi, and the traditional open approach, and considering healthcare direct costs associated with the intervention and the short-term post-operative course. MATERIALS AND METHODS: Twenty RPD and 194 OPD performed between January 2011 and December 2020 by the same operator at our high-volume multidisciplinary center for robot-assisted surgery and for pancreatic surgery, were retrospectively analyzed. Two comparable groups of 20 patients (Xi-RPD-group) and 40 patients (OPD-group) were obtained matching 1:2 the RPD-group with the OPD-group. Perioperative data and overall costs, including overall variable costs (OVCs) and fixed costs, were compared. RESULTS: No difference was reported in mean operative time: 428 min for Xi-RPD-group versus 404 min for OPD, p = 0.212. The median overall length of hospital stay was significantly lower in the Xi-RPD-group: 10 days versus 16 days, p = 0.001. In the Xi-RPD-group, consumable costs were significantly higher (€6149.2 versus €1267.4, p < 0.001), while hospital stay costs were significantly lower: €5231.6 versus €8180 (p = 0.001). No significant differences were found in terms of OVCs: €13,483.4 in Xi-RPD-group versus €11,879.8 in OPD-group (p = 0.076). CONCLUSIONS: Robot-assisted surgery is more expensive because of higher acquisition and maintenance costs. However, although RPD is associated to higher material costs, the advantages of the robotic system associated to lower hospital stay costs and the absence of difference in terms of personnel costs thanks to the similar operative time with respect to OPD, make the OVCs of the two techniques no longer different. Hence, the higher costs of advanced technology can be partially compensated by clinical advantages, particularly within a high-volume multidisciplinary center for both robot-assisted and pancreatic surgery. These preliminary data need confirmation by further studies.

Trajectories of Adherence to Biologic Disease-Modifying Anti-Rheumatic Drugs in Tuscan Administrative Databases: The Pathfinder Study.

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.

Cost-effectiveness of treatment optimisation with biomarkers for immunotherapy in solid tumours: a systematic review protocol.

INTRODUCTION: The combination of biomarkers and drugs is the subject of growing interest both from regulators, physicians and companies. This study protocol of a systematic review is aimed to describe available literature evidences about the cost-effectiveness, cost-utility or net-monetary benefit of the use of biomarkers in solid tumour as tools for customising immunotherapy to identify what further research needs. METHODS AND ANALYSIS: A systematic review of the literature will be carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed and Embase will be queried from June 2010 to June 2021. The PICOS model will be applied: target population (P) will be patients with solid tumours treated with immune checkpoint inhibitors (ICIs); the interventions (I) will be test of the immune checkpoint predictive biomarkers; the comparator (C) will be any other targeted or non-targeted therapy; outcomes (O) evaluated will be health economic and clinical implications assessed in terms of incremental cost-effectiveness ratio, net health benefit, net monetary benefit, life years gained, quality of life, etc; study (S) considered will be economic evaluations reporting cost-effectiveness analysis, cost-utility analysis, net-monetary benefit. The quality of the evidence will be graded according to Grading of Recommendations Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: This systematic review will assess the cost-effectiveness implications of using biomarkers in the immunotherapy with ICIs, which may help to understand whether this approach is widespread in real clinical practice. This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020201549.

Prognostic value of stress echocardiography assessed by the ABCDE protocol.

AIM: The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. METHODS AND RESULTS: From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13-36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B-E steps (P < 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. CONCLUSION: ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis.

OBJECTIVES: To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). METHODS: We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. RESULTS: Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). CONCLUSION: Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. KEY POINTS: • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Cost-Effectiveness of Direct Non-Vitamin K Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Patients with Non-Valvular Atrial Fibrillation Based on Available "Real-World" Evidence: The Italian National Health System Perspective.

BACKGROUND AND OBJECTIVE: The increasing availability of real-world evidence (RWE) about safety and effectiveness of direct non-vitamin K oral anticoagulants (DOACs) for the management of atrial fibrillation (AF) offers the opportunity to better understand the clinical and economic implications of DOACs versus vitamin K antagonists (VKAs). The objective of this study was to compare the economic implications of DOACs and VKAs using data from real-world evidence in patients with AF. METHODS: A Markov model simulating the lifetime course of patients diagnosed with non-valvular AF was used to evaluate the cost-effectiveness of DOACs (i.e., rivaroxaban, dabigatran and apixaban) versus VKAs from the Italian National Health System (INHS) perspective. The model was made up of data from the literature and a meta-analysis of RWE on the incidence of stroke/systemic embolism (SE), major bleeding (MB), intracranial haemorrhage (ICH) and all-cause mortality (ACM); direct costs included drug costs, costs for drug monitoring, and management of events from official national lists. One-way and probabilistic sensitivity analyses (PSA) were used to assess the robustness of the results. RESULTS: Results from the meta-analysis showed that apixaban had a high probability of being the most effective for stroke/SE, MB and ACM. Despite their higher acquisition costs, the cost-effectiveness analysis showed all DOACs involved a saving when compared with VKAs, with per-patient savings ranging between €4647 (rivaroxaban) to €6086 (apixaban). Moreover, all DOACs indicated a gain both in quality-adjusted life-years and life-years. According to PSA, findings related to apixaban were consistent, while for dabigatran and rivaroxaban PSA revealed a higher degree of uncertainty. CONCLUSIONS: The beneficial effect of DOACs on containing events showed in RWE had the potential to offset drug-related costs, thus improving the sustainability of treatment for non-valvular AF in daily clinical practice.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

Coronary Flow Velocity Reserve Reduction Is Associated with Cardiovascular, Cancer, and Noncancer, Noncardiovascular Mortality.

BACKGROUND: Coronary flow velocity reserve (CFVR) measured in the left anterior descending artery during high-dose vasodilator stress echocardiography interrogates both epicardial and microcirculatory coronary function and has been inversely associated with chronic inflammation and microvascular dysfunction, as well as with the presence of obstructive coronary artery disease. Microvascular dysfunction and chronic inflammation are common mechanisms of disease in cardiovascular (CV) and non-CV conditions. We aimed to assess whether CFVR is associated with all-cause death, but more specifically with CV, cancer, and non-CV and noncancer (NCVNC) mortality, independently and increasingly over other demographic, clinical, and echocardiography variables. METHODS: One thousand two patients who underwent stress echocardiography were followed for a median of 8.2 years, with clinical, regional wall motion abnormalities (RWMAs), and CFVR data. The independent prognostic value of RWMA and CFVR regarding CV, cancer, or NCVNC mortality was evaluated adjusting for clinical variables. A prespecified subgroup of subjects with no RWMA or revascularization procedures during follow-up was also analyzed (n = 752), to exclude most participants with possible coronary artery disease and remove such confounding from the assessment of the potential association of CFVR and mortality. RESULTS: A total of 161 patients (16%) died, 63 deaths being CV (39%), 52 from cancer (32%), and 46 (29%) from NCVNC causes. In comparison to CV mortality, cancer and NCVNC mortality were not associated with an ischemic RWMA at univariable analysis, while a CFVR < 2 was significantly associated with each category of cause-specific mortality. A CFVR < 2 or ≥2 separated a group of patients with 8-year 14.6% versus 1.2% CV mortality, 10.3% versus 0.4% cancer mortality, and 9.5% versus 1.5% NCVNC mortality. CONCLUSIONS: The reduction of CFVR is independently associated with CV, cancer, and NCVNC death in a population clinically referred for suspected/known coronary artery disease. CFVR can act as a marker or a mechanism preceding and predicting mortality from a wide variety of diseases.

Standard echocardiography versus very-low mechanical index contrast-imaging: left ventricle volumes and ejection fraction multi-reader variability and reference values in a subgroup with no risk factors or cardiac disease.

We retrospectively assessed the rest-phase images of 300 contrast stress- echocardiograms, during which very-low mechanical index (VLMI) imaging with ultrasound enhancing agents (UEAs) was routinely acquired in addition to greyscale echocardiography; intra- and inter-reader variability for left ventricle (LV) volumes and ejection fraction (LVEF) at rest was established in the overall cohort and normal values were calculated in the subset of subjects with no cardiac risk factors or cardiac disease and a normal stress-echocardiogram. Current recommendations for chamber quantification using echocardiography advise the use of UEAs in case of insufficient quality of endocardial visualization, but normal values for LV volumes and LVEF using UEAs have never been published using currently recommended VLMI method. Single-centre retrospective study, enrolling subjects referred to contrast stress- echocardiography for suspect coronary artery disease, including the acquisition of both standard 2D greyscale and bolus UEAs with VLMI, regardless of the image quality. This enables offline measurement of the LV volumes and LVEF for both greyscale and UEAs-VLMI images at rest in all subjects. Images were allocated to 3 readers in random order. Normal range for LV volumes and LVEF was also derived in a subset of apparently healthy subjects. In the 298 exams finally assessed, measurement variability among the three readers was lower with UEAs-VLMI, in particular for end-systolic volumes (intra-class correlation coefficient for concordance improved from 0.855 to 0.916, for LVEF from 0.68 to 0.783, p < 0.01), intra- observer variability reduced (Lin's correlation coefficient for LVEF from 0.747 to 0.857, p < 0.01). Normal mean indexed LV end-diastolic volume with UEAs-VLMI, compared to greyscale imaging, was + 14 ml/m2, while LVEF was + 5 to + 6% points. This is the largest study specifically addressing UEAs-VLMI imaging and comparing data with standard greyscale imaging; it demonstrates a reduction in measurement variability of LV volumes and LVEF. Normal reference values for VLMI ultrasound are reported for the first time in comparison with greyscale values.

Structured cost analysis of robotic TME resection for rectal cancer: a comparison between the da Vinci Si and Xi in a single surgeon's experience.

BACKGROUND: Robotic-assisted surgery by the da Vinci Si appears to benefit rectal cancer surgery in selected patients, but still has some limitations, one of which is its high costs. Preliminary studies have indicated that the use of the new da Vinci Xi provides some added advantages, but their impact on cost is unknown. The aim of the present study is to compare surgical outcomes and costs of rectal cancer resection by the two platforms, in a single surgeon's experience. METHODS: From April 2010 to April 2017, 90 robotic rectal resections were performed, with either the da Vinci Si (Si-RobTME) or the da Vinci Xi (Xi-RobTME). Based on CUSUM analysis, two comparable groups of 40 consecutive Si-RobTME and 40 consecutive Xi-RobTME were obtained from the prospectively collected database and used for the present retrospective comparative study. Data costs were analysed based on the level of experience on the proficiency-gain curve (p-g curve) by the surgeon with each platform. RESULTS: In both groups, two homogeneous phases of the p-g curve were identified: Si1 and Xi1: cases 1-19, Si2 and Xi2: cases 20-40. A significantly higher number of full RAS operations were achieved in the Xi-RobTME group (p < 0.001). A statistically significant reduction in operating time (OT) during Si2 and Xi2 phase was observed (p < 0.001), accompanied by reduced overall variable costs (OVC), personnel costs (PC) and consumable costs (CC) (p < 0.001). All costs were lower in the Xi2 phase compared to Si2 phase: OT 265 versus 290 min (p = 0.052); OVC 7983 versus 10231.9 (p = 0.009); PC 1151.6 versus 1260.2 (p = 0.052), CC 3464.4 versus 3869.7 (p < 0.001). CONCLUSIONS: Our experience confirms a significant reduction of costs with increasing surgeon's experience with both platforms. However, the economic gain was higher with the Xi with shorter OT, reduced PC and CC, in addition to a significantly larger number of cases performed by the fully robotic approach.

Brief Report: How Do Patients With Newly Diagnosed Systemic Lupus Erythematosus Present? A Multicenter Cohort of Early Systemic Lupus Erythematosus to Inform the Development of New Classification Criteria.

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with nonspecific signs and symptoms that are also found in other conditions. This study aimed to evaluate manifestations at disease onset and to compare early SLE manifestations to those of diseases mimicking SLE. METHODS: Academic lupus centers in Asia, Europe, North America, and South America collected baseline data on patients who were referred to them during the previous 3 years for possible SLE and who had a symptom duration of <1 year. Clinical and serologic manifestations were compared between patients diagnosed as having SLE and those diagnosed as having SLE-mimicking conditions. Diagnostic performance of the 1997 American College of Rheumatology (ACR) SLE classification criteria and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria was tested. RESULTS: Data were collected on 389 patients with early SLE and 227 patients with SLE-mimicking conditions. Unexplained fever was more common in early SLE than in SLE-mimicking conditions (34.5% versus 13.7%, respectively; P < 0.001). Features less common in early SLE included Raynaud's phenomenon (22.1% versus 48.5%; P < 0.001), sicca symptoms (4.4% versus 34.4%; P < 0.001), dysphagia (0.3% versus 6.2%; P < 0.001), and fatigue (28.3% versus 37.0%; P = 0.024). Anti-double-stranded DNA, anti-ß2 -glycoprotein I antibodies, positive Coombs' test results, autoimmune hemolytic anemia, hypocomplementemia, and leukopenia were more common in early SLE than in SLE-mimicking conditions. Symptoms detailed in the ACR and SLICC classification criteria were significantly more frequent among those with early SLE. Fewer patients with early SLE were not identified as having early SLE with use of the SLICC criteria compared to the ACR criteria (16.5% versus 33.9%), but the ACR criteria demonstrated higher specificity than the SLICC criteria (91.6% versus 82.4%). CONCLUSION: In this multicenter cohort, clinical manifestations that could help to distinguish early SLE from SLE-mimicking conditions were identified. These findings may aid in earlier SLE diagnosis and provide information for ongoing initiatives to revise SLE classification criteria.

Gastroesophageal reflux symptoms among Italian university students: epidemiology and dietary correlates using automatically recorded transactions.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. METHODS: A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. RESULTS: We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. DISCUSSION: The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. CONCLUSIONS: To our knowledge, this is the first study evaluating the prevalence of typical GERD-related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system.