Colorectal Cancer Screening: Tests, Strategies, and Perspectives

Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66–90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed

Diffusion of good practices of care and decline of the association with case volume: the example of breast conserving surgery

<p>Abstract</p> <p>Background</p> <p>Several previous studies conducted on cancer registry data and hospital discharge records (HDR) have found an association between hospital volume and the recourse to breast conserving surgery (BCS) for breast cancer. The aim of the current study is to depict concurrent time trends in the recourse to BCS and its association with hospital volume.</p> <p>Methods</p> <p>Admissions of breast cancer patients for BCS or mastectomy in the period 2000–2004 were identified from the discharge database of the Veneto Region (Italy). The role of procedural volume (low < 50, medium 50–100, high > 100 breast cancer surgeries/year), and of individual risk factors obtainable from HDR was assessed through a hierarchical log-binomial regression.</p> <p>Results</p> <p>Overall, the recourse to BCS was higher in medium (risk ratio = 1.12, 95% confidence interval 1.07–1.18) and high-volume (1.09, 1.03–1.14) compared to low-volume hospitals. The proportion of patients treated in low-volume hospitals dropped from 22% to 12%, with a concurrent increase in the activity of medium-volume providers. The increase over time in breast conservation (globally from 56% to 67%) was steeper in the categories of low- and medium-volume hospitals with respect to high caseload.</p> <p>Conclusion</p> <p>The growth in the recourse to BCS was accompanied by a decline of the association with hospital volume; larger centers probably acted as early adopters of breast conservation strategies that subsequently spread to smaller providers.</p

Relationship between hospital volume and short-term outcomes: A nationwide population-based study including 75,280 rectal cancer surgical procedures

There is growing interest on the potential relationship between hospital volume (HV) and outcomes as it might justify the centralization of care for rectal cancer surgery. From the National Italian Hospital Discharge Dataset, data on 75,280 rectal cancer patients who underwent elective major surgery between 2002 and 2014 were retrieved and analyzed. HV was grouped into tertiles: low-volume performed 1-12, while high-volume hospitals performed 33+ procedures/year. The impact of HV on in-hospital mortality, abdominoperineal resection (APR), 30-day readmission, and length of stay (LOS) was assessed. Risk factors were calculated using multivariate logistic regression. The proportion of procedures performed in low-volume hospitals decreased by 6.7 percent (p<0.001). The rate of in-hospital mortality, APR and 30-day readmission was 1.3%, 16.3%, and 7.2%, respectively, and the median LOS was 13 days. The adjusted risk of in-hospital mortality (OR = 1.49, 95% CI = 1.25-1.78), APR (OR 1.10, 95%CI 1.02-1.19), 30-day readmission (OR 1.49, 95%CI 1.38-1.61), and prolonged LOS (OR 2.29, 95%CI 2.05-2.55) were greater for low-volume hospitals than for high-volume hospitals. This study shows an independent impact of HV procedures on all short-term outcome measures, justifying a policy of centralization for rectal cancer surgery, a process which is underwa

Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test. The EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)

OBJECTIVES: To assess variation in the main colonoscopy quality indicators in organised colorectal cancer (CRC) screening programmes based on faecal immunochemical test (FIT). DESIGN: Data from a case-series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected. The adenoma detection rate (ADR) and caecal intubation rate (CIR) were assessed for the whole population and the individual endoscopists. To explore variation in the quality indicators, multilevel analyses were performed according to patient/centre/endoscopist characteristics. RESULTS: We analysed 75 569 (mean age: 61.3 years; men: 57%) colonoscopies for positive FIT performed by 479 endoscopists in 79 centres. ADR ranged from 13.5% to 75% among endoscopists (mean: 44.8%). ADR was associated with gastroenterology specialty (OR: 0.87 for others, 95% CI 0.76 to 0.96) and, at the endoscopy centre level, with the routine use of sedation (OR: 0.80 if occasional (600 colonoscopies; 95% CI 1.11 to 2.04) and, at the endoscopy centre level, screening-dedicated sessions (OR: 2.18; 95% CI 1.24 to 3.83) and higher rates of sedation (OR: 0.47 if occasional; 95% CI 0.24 to 0.92). CONCLUSIONS: The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

Failure to rescue as a source of variation in hospital mortality after rectal surgery: The Italian experience

INTRODUCTION: Failure to rescue (FTR) patients from postoperative complications could contribute to the variability in surgical mortality seen among hospitals with different volumes. We sought to examine the impact of complications and FTR on mortality following rectal surgery. METHODS: The National Italian Hospital Discharge Dataset allowed to identify 75,280 patients who underwent rectal surgery between 2002 and 2014. Hospital volume was stratified into tertiles. Rates of major complications, FTR from complications and mortality following rectal surgery were compared. RESULTS: During the study period, both the incidence of complications (2002, 23.7% versus 2014, 21.2%), and FTR decreased overtime (2002, 6.9% versus 2014, 3.8%) (both P\u202f<\u202f0.001). The complication rate was 24.4% in low-, 21.6% in intermediate- and 20.4% in high-volume hospitals (P\u202f<\u202f0.001). Complications were less common in minimally invasive surgery (MIS) versus open cases (18.2% versus 23.2%; P\u202f<\u202f0.001). The most frequent complications included prolonged ileus or small bowel obstruction (5.3%), and anemia requiring blood transfusions (5.3%). The rate of FTR was 5.5%, 5.6% and 3.7% for low-, intermediate- and high-volume hospitals, respectively (P\u202f<\u202f0.001). FTR after MIS was 2.6% vs. 5.5% after open surgery (P\u202f<\u202f0.001). After accounting for patient and hospital characteristics, patients treated at low-volume hospitals were 23% more likely to die after a complication, compared to patients at high-volume hospitals (OR 1.23, 95%CI 1.13-1.33). CONCLUSIONS: Hospital volume is the strongest predictor of complication and FTR. The reduction in mortality in high-volume hospitals could be determined by the better ability to rescue patients. These findings support the centralization policy of rectal cancer treatment

Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared

During the COVID-19 pandemic, excess mortality has been reported worldwide, but its magnitude has varied depending on methodological differences that hinder between-study comparability. Our aim was to estimate variability attributable to different methods, focusing on specific causes of death with different pre-pandemic trends. Monthly mortality figures observed in 2020 in the Veneto Region (Italy) were compared with those forecasted using: (1) 2018–2019 monthly average number of deaths; (2) 2015–2019 monthly average age-standardized mortality rates; (3) Seasonal Autoregressive Integrated Moving Average (SARIMA) models; (4) Generalized Estimating Equations (GEE) models. We analyzed deaths due to all-causes, circulatory diseases, cancer, and neurologic/mental disorders. Excess all-cause mortality estimates in 2020 across the four approaches were: +17.2% (2018–2019 average number of deaths), +9.5% (five-year average age-standardized rates), +15.2% (SARIMA), and +15.7% (GEE). For circulatory diseases (strong pre-pandemic decreasing trend), estimates were +7.1%, −4.4%, +8.4%, and +7.2%, respectively. Cancer mortality showed no relevant variations (ranging from −1.6% to −0.1%), except for the simple comparison of age-standardized mortality rates (−5.5%). The neurologic/mental disorders (with a pre-pandemic growing trend) estimated excess corresponded to +4.0%/+5.1% based on the first two approaches, while no major change could be detected based on the SARIMA and GEE models (−1.3%/+0.3%). The magnitude of excess mortality varied largely based on the methods applied to forecast mortality figures. The comparison with average age-standardized mortality rates in the previous five years diverged from the other approaches due to the lack of control over pre-existing trends. Differences across other methods were more limited, with GEE models probably representing the most versatile option

Ventricular arrhythmias in young competitive athletes: Prevalence, determinants, and underlying substrate

Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes.Background--Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes. Method and Results--We studied 288 competitive athletes (age range, 16-35 years; median age, 21 years) and 144 sedentary individuals matched for age and sex who underwent 12-lead 24-hour ambulatory electrocardiographic monitoring. VAs were evaluated in terms of number, complexity (ie, couplet, triplet, or nonsustained ventricular tachycardia), exercise inducibility, and morphologic features. Twenty-eight athletes (10%) and 13 sedentary individuals (11%) showed > 10 isolated premature ventricular beats (PVBs) or 651 complex VA (P=0.81). Athletes with > 10 isolated PVBs or 651 complex VA were older (median age, 26 versus 20 years; P=0.008) but did not differ with regard to type of sport, hours of training, and years of activity compared with the remaining athletes. All athletes with > 10 isolated PVBs or 651 complex VA had a normal echocardiographic examination; 17 of them showing > 500 isolated PVBs, exercise-induced PVBs, and/or complex VA underwent additional cardiac magnetic resonance, which demonstrated nonischemic left ventricular late gadolinium enhancement in 3 athletes with right bundle branch block PVBs morphologic features. Conclusions--The prevalence of > 10 isolated PVBs or 651 complex VA at 24-hour ambulatory electrocardiographic monitoring did not differ between young competitive athletes and sedentary individuals and was unrelated to type, intensity, and years of sports practice. An underlying myocardial substrate was uncommon and distinctively associated with right bundle branch block VA morphologic features

Relationship between electrocardiographic findings and cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy

Background-\u2014The new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated the relationship between electrocardiographic findings and contrast-enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy. Methods and Results-\u2014We studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast-enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T-wave inversion across a 12-lead ECG and increasing values of median right ventricular (RV) end-diastolic volume (P55 ms in the right precordial leads (V1-V3) was associated with higher RV volume (P=0.014) and lower RV ejection fraction (P=0.053). Low QRS voltages in limb leads predicted the presence (P=0.004) and amount (P<0.001) of left ventricular late gadolinium enhancement. Conclusions-\u2014The study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients

Introduction The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. Objective The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. Methods This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. Results Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. Conclusions ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n\u2009=\u2009305,044), while 42% of prevalent women had breast cancer (n\u2009=\u2009604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since 6515 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+\u200937% vs 2010). The largest 10-year increases are foreseen for prostate (+\u200985%) and for thyroid cancers (+\u200979%), and for long-term survivors diagnosed since 20 or more years (+\u200945%). Among the population aged 6575 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation need