Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise.

BACKGROUND: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. PATIENTS AND METHODS: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. RESULTS: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). CONCLUSION: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended. CLINICAL TRIALS REGISTRATION NUMBER: CRO-2010-17.

Hospital Anxiety and Depression Scale (HADS) accuracy in cancer patients.

PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is a self-report questionnaire designed to screen anxious and depressive states in patients in non-psychiatric settings. In spite of its large use, no agreement exists in literature on HADS accuracy in case finding. The present research addresses the issue of HADS accuracy in cancer patients, comparing its two subscales (HADS-A and HADS-D) against tools not in use in psychiatry, which are able to detect prolonged negative emotional states. METHODS: 2121 consecutive adult cancer inpatients were administered the HADS together with the State Anxiety subscale of State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Scale on Depression. Receiver operating characteristic (ROC) curves were computed to identify a cut-off for anxious and depressive states in cancer patients. All indicators were computed together with their corresponding 95% confidence interval (95% CI). RESULTS: Data of 1628 and 1035 participants were used to assess the accuracy in case finding of HADS-A and HADS-D, respectively. According to the ROC analysis, the optimal cut-off was > 9 units for the HADS-A and > 7 units for the HADS-D. The area under the ROC curve was 0.90 for HADS-A (95% CI 0.88-0.91) and 0.84 for HADS-D (95% CI 0.81-0.86). CONCLUSIONS: This study suggested that risk scores of anxious and depressive states above specific HADS cut-offs are useful in identifying anxious and depressive states in cancer patients, and they may thus be applicable in clinical practice.

[Mortality Atlas of the Campania Region. All-cause and cause-specific mortality at municipal level, 2006-2014]. / Atlante di mortalità della regione Campania. Mortalità generale e specifica per causa, con dettaglio comunale, periodo 2006-2014.

OBJECTIVES: This Monograph aims to provide the scientific community and the Regional Healthcare Service an up-to-date Atlas of mortality for the Campania Region (Southern Italy). The Atlas shows an overview of mortality through comparisons with national data and with intraregional macroareas. Maps presenting risk measures with municipal details are also provided. MATERIALS AND METHODS: Both overall and cause-specific mortality data for the period 2006-2014 referred to people residing in Campania Region are analysed in this Atlas. Twenty-nine death causes (major causes and specific cancers) are studied; for each of them, it has been provided: • direct standardised rates (standard population EU 2013) referred to Italy, Campania Region, and the seven regional Local Health Units (LHUs); • standardised mortality ratios (SMRs), estimated on a regional basis, referred to every LHU; • years of life lost (number and rate) both on a regional and on LHU basis; • mortality rate trends for the period 2006-2014, including annual percentage changes (APCs) for Italy, Campania Region, and every LHU; • for every death cause, regional maps are provided also with municipal details for Relative Risks (RRs) and risk posterior probabilities (PPs) estimated through a Bayesian hierarchical model. Risk estimates are presented both crude and adjusted by socioeconomic deprivation index resulted from the 2011 Census of the Italian National Institute fo Statistics. RESULTS: In Campania Region, standardised mortality ratios (per 100,000; IC95%) higher than the national average have been recorded for the following causes: all causes of death: M: 1,233.3 (IC95% 1,227.9-1,238.9) vs 1,093.8 (IC95% 1,092.5-1,095.1); F: 826.1 (IC95% 822.6-829.7) vs 722.8 (IC95% 721.9-732.6); digestive system diseases: M: 51.2 (IC95% 50.2-52.3) vs 44.2 (IC95% 44.0-44.5); F: 35.8 (IC95% 35.1-36.6) vs 29,2 (IC95% 29.0-29.4); circulatory system diseases: M: 493.1 (IC95% 489.6-496.8) vs 404.3 (IC95% 403.5-405.1); F: 388.5 (IC95% 386.1-390.9) vs 296.5 (IC95% 295.9-297.0); genitourinary system diseases: M: 27.2 (IC95% 26.4-28.1) vs 21.9- (IC95% 21.7-22.1); F: 18.2 (IC95% 17.7-18.7) vs 13.7- (IC95% 13.5-13.8); endocrine and metabolic diseases: M: 60.0 (IC95% 58.8-61.2) vs 43.8 (IC95% 43.5-44.0); F: 60.7 (IC95% 59.8-61.7) vs 36.6 (IC95% 36.4-36.8); myocardial infarction: M: 71.1 (IC95% 69.8-72.4) vs 60.9 (IC95% 60.6-61.2); F: 38.2 (IC95% 37.4-39.0) vs 30.2-(IC95% 30.0-30.4); diabetes: M: 52.6 (IC95% 51.5-53.8) vs 35.1 (IC95% 34.9-35.3); F: 53.8 (IC95% 52.9-54.7) vs 28.6 (IC95% 28.4-28.8). On the other hand, mortality rates comparable to or lower than the national average are observed for the remaining causes of death, with different differences for gender. Mortality for cancer causes in Campania Region presents rates higher than the rates observed at national level in males for the following causes: all cancers: 380.4 (IC95% 377.5-383.3) vs 356.5 (IC95% 355.8-357.2); lung cancer: 112.5 (IC95% 110.9/114.0) vs 93.0 (IC95% 92.6-93.3);larynx cancer: 7.6 (IC95% 7.2-8.0) vs 5.5 (IC95% 5.4-5.6);bladder cancer: 25.1 (IC95% 24.4-25.9) vs 17.3 (IC95% 17.1-17.4); in females for the following causes: liver cancer: 3.8 (IC95% 3.6-4.1) vs 3.3 (IC95% 3.2-3.4);bladder cancer:: 3.5 (IC95% 3.3-3.7) vs 3.0 (IC95% 2.9-3.0). In Campania Region, mortality rates comparable to or lower than the national average are observed for the remaining cancer causes both in females and in males. For almost all the death causes, the highest mortality rates are observed in the three LHUs of Naples (Naples centre, Naples 2 North, Naples 3 South); for some death causes, also the Province of Caserta presents the highest mortality rates. It is worth noting that these areas are characterised by the highest urbanisation and regional population density, and by exposures to possible environmental risks. Time trend analyses highlight that regional and national trends are similar for almost all the examined death causes. In Campania Region, males present decreasing trends for all-cause mortality; for respiratory system, circulatory system, and digestive system diseases; for all malignant cancers; for lung, prostate, and stomach cancers; for leukaemias. On the other hand, an increasing trend is shown for liver cancer. Trends for genitourinary system and nervous system diseases are almost unchanged; the same is for blood diseases and haemolymphopoietic system cancers. In females, there is a decreasing mortality trend for all causes, for circulatory system and digestive system diseases; for haemolymphopoietic system and stomach cancers; on the contrary, an increasing trend is highlighted for communicable diseases and lung and liver cancer, mirroring the national situation. Trends for respiratory system, genitourinary system, nervous system diseases; blood diseases; all malignant cancers; kidney and breast cancers; leukaemias are almost unchanged. The analysis of mortality data on municipal basis reported that the most excesses in mortality risk occur in the municipalities included in the area with the highest urban development of Naples and, partly, in the municipalities of the Caserta Province. The distribution of the excesses at municipal level is not homogeneous in Campania Region, but there are relevant intermunicipal differences related to the considered causes of death. This heterogeneity in the distribution of excess risk is a characteristic also of the area called Terra di fuochi (Land of fires), both for overall mortality and for mortality by gender. CONCLUSIONS: Mortality data are a valuable support to the analysis of the population health conditions. Excesses in general mortality and for some specific causes found in Campania Region vs Italy in 2006-2014 suggest that in this region there is a need to implement more strict intervention in terms both of primary prevention (for individuals and the environment) and of management of the whole care and clinical pathway of some pathologies, bearing in mind the burden of regional structural and economic factors on these excesses. The highest excesses in mortality in Campania Region have been found in the areas with the highest degree of urbanisation: this confirms the national data of a different distribution of diseases - and mortality - in the areas characterised by high urban development compared to rural areas. Finally, cause-specific mortality maps at municipal level, extended to the whole region, could enable to identify possible critical issues which may need epidemiological studies focused on possible local factors of environmental pressure.

Patients and caregivers' unmet information needs in the field of patient education: results from an Italian multicenter exploratory survey.

Patient education and empowerment (PEE) is aimed at improving competence of patients during their clinical path and enabling healthcare providers with specific communication strategies. We investigated the interest of Italian Cancer Research & Care Centers (CRCI) users (patients and caregivers) in being involved in PEE activities. An anonymous questionnaire addressed to users was distributed between June 2013 and February 2014. The questionnaire gathered information on the following: health-related topics; 13 different PEE initiatives/modalities of learning already active at CRCI; personal demographic data; the willingness to be more involved in the organization of health services provided and in which context; and five preferred info-educational activities. Frequency distribution and chi-square analysis were computed. Statistical significance (p value) was set at < 0.05. A total of 875 (29%) users responded to the 3000 distributed questionnaires. The first three priorities of interest were "early diagnosis" (18%), "prevention" (17%), and "diagnosis explanation" (13%). The first three priorities on informational activity were as follows: "classes on cancer-related topics with healthcare professionals" (28%); "cancer information service" (22%); "drug information point" (7%). Forty-nine percent of the respondents stated that they would like to be involved in the organization of PEE activities, particularly caregivers and users older than 55 years of age. The preferred educational activities were "classes on cancer-related topics with healthcare professionals" and "cancer information service" on a face-to-face modality. Patients were more interested than caregivers in "prevention." The extension of PEE programs to all CRCI users into routine care will be the next step of the present research.

Survival after the diagnosis of breast or colorectal cancer in the GAZA Strip from 2005 to 2014.

BACKGROUND: Within a dramatic socio-political context, cancer represents a growing health burden in the Gaza Strip. We investigated the survival experience of people diagnosed with breast (BC) or colorectal (CRC) cancer from 2005 to 2014. METHODS: Data included 1360 BC cases (median age 55.1 years) and 722 CRC cases (median age: 59.5 years; 52.5% men) recorded by the Gaza Cancer Registry according to a standard protocol. Clinical information was available for cases diagnosed in 2005-2006 only. Survival probabilities were estimated by Kaplan-Meyer method, while hazard ratios (HRs) and 95% confidence intervals (CI), adjusted for age and sex, were computed to assess factors associated with the risk of death. RESULTS: Five-year survival was 65.1% for women with BC and 50.2% for patients with CRC. Advanced age (> 65 years), stage, and grade increased the death risk. Full access to therapies was associated with a reduced risk of death as compared with patients who had limited access (HR = 0.26, 95% CI:0.13-0.51 for BC; and HR = 0.11, 95% CI:0.04-0.31 for CRC). CONCLUSION(S): The 5-year survival after BC or CRC in the Gaza Strip was in line with estimates from surrounding Arab countries, but it was much lower than in developed Mediterranean countries (e.g., in Italy or in Jewish people in Israel).

Sleep disorders in children with brain tumors: a pilot study based on a sleep disorder questionnaire.

PURPOSE: The aim of this study is to compare the prevalence of sleep disorders (SD) between children treated for brain tumors and healthy children, and to define the type of SD. METHODS: A case-control study was performed from October 2014 to April 2015. Inclusion criteria were patients between 2 and 16 years with "cases" defined as children affected by central nervous system tumors at least 3 months after the end of treatment (surgery and/or radiotherapy and/or chemotherapy) at the time of evaluation and "controls" as healthy children. Children's sleep quality was assessed with a questionnaire administered to parents (Child's Sleep Habits Questionnaire, CSHQ). A total score greater than 41 is suggestive for the presence of disturbed sleep. The risk of SD was estimated by the odds ratio (OR) and their 95% confidence intervals (95% CI) through logistic regression models. RESULTS: Twenty-nine cases and 87 controls (in a 1:3 model) were enrolled, for a total of 116 subjects. The prevalence of SD resulted of 82.8% among cases and 64.4% in controls. A statistically significant difference between the two groups (OR 2.65; 95% CI 0.92-7.65) was not reached. Analyzing singular disturbances, parasomnias and night awakenings showed a statistically significant difference between the two groups (OR 4.32; 95% CI 1.08-17.34). CONCLUSIONS: Our study revealed a trend toward SD in children with brain tumor when compared to healthy population. Hovewer, analyzing specific subtypes of SD some significant differences were obtained. A significant difference was obtained only for specific subtypes of SD. Further investigations could better define the real burden of SD.

Molecular and Pathological Features of Gastric Cancer in Lynch Syndrome and Familial Adenomatous Polyposis.

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are autosomal dominant hereditary diseases caused by germline mutations leading to the development of colorectal cancer. Moreover, these mutations result in the development of a spectrum of different tumors, including gastric cancers (GCs). Since the clinical characteristics of GCs associated with LS and FAP are not well known, we investigated clinical and molecular features of GCs occurring in patients with LS and FAP attending our Institution. The Hereditary Tumor Registry was established in 1994 at the Department of Oncologic Gastroenterology, CRO Aviano National Cancer Institute, Italy. It includes 139 patients with LS and 86 patients with FAP. Patients were recruited locally for prospective surveillance. Out of 139 LS patients, 4 developed GC­3 in the presence of helicobacter pylori infection and 1 on the background of autoimmune diseases. All GCs displayed a high microsatellite instability (MSI-H) and loss of related mismatch repair (MMR) protein. One of the FAP patients developed a flat adenoma, displaying low-grade dysplasia at the gastric body, and another poorly differentiated adenocarcinoma with signet ring cells like Krukenberg without HP infection. LS carriers displayed a risk of GC. The recognition of HP infection and autoimmune diseases would indicate those at higher risk for an endoscopic surveillance. Regarding FAP, the data suggested the need of suitable endoscopic surveillance in long survivals with diffuse fundic gland polyps.

Low glycemic index diet, exercise and vitamin D to reduce breast cancer recurrence (DEDiCa): design of a clinical trial.

BACKGROUND: Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. METHODS: Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DISCUSSION: DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. TRIAL REGISTRATION: May 11, 2016; NCT02786875 . EUDRACT NUMBER: 2015-005147-14.

Long-Term Outcome of Rectal Cancer With Clinically (EUS/MRI) Metastatic Mesorectal Lymph Nodes Treated by Neoadjuvant Chemoradiation: Role of Organ Preservation Strategies in Relation to Pathologic Response.

BACKGROUND: Organ preservation strategies are under investigation for patients with locally advanced rectal cancer (LARC) who achieve a complete pathologic response in the primary tumor (ypT0) after neoadjuvant chemoradiation therapy (CRT). This study explored the value of this approach for cN+ patients. METHODS: Data were retrieved from our institutional prospective rectal cancer database. Tumors with mesorectal lymph nodes larger than 5 mm shown on endorectal ultrasonography, pelvic magnetic resonance imaging, or both were staged as cN+. RESULTS: The study population comprised 226 patients (142 men and 84 women; median age, 64 years) with LARC who underwent CRT followed by surgery including total mesorectal excision (TME) (n = 179) and full-thickness local excision (LE) (n = 47) between 1996 and 2013. At staging, 123 patients (54.4 %) were cN+. In 65 cases (28.7 %), ypCR was observed. Metastatic mesorectal lymph nodes (ypN+) were detected in 41.6 % of the cN+ patients and in 2.8 % of the cN0 patients (P < 0.01). Among the cN+ patients, 16 % of the ypT0 cases were ypN+ compared with 51.8 % of the no-ypT0 cases (P < 0.01). Among the cN+ patients who underwent TME, the 5-year disease-specific survival (DSS) and disease-free survival (DFS) rates were respectively 100 and 91.6 % for the ypT0 patients compared with 71.2 and 58.0 % for the no-ypT0 patients (P = 0.01). Among the ypN+ patients, the 5-year DSS and DFS rates were both 100 % for the ypT0 cases compared with 59.1 and 43.3 % for the no-ypT0 patients. Among the cN+ and ypT0 patients, the 5-year DSS and DFS were respectively 100 and 85.7 % for the TME patients compared with 100 and 91.6 % for the LE patients. In the multivariate analysis, ypT0 was the only independent prognostic factor. CONCLUSIONS: Protocols aimed at organ preservation in LARC that achieve ypT0 after CRT can be offered also to cN+ patients.

Cell-free DNA as a prognostic marker in stage I non-small-cell lung cancer patients undergoing stereotactic body radiotherapy.

OBJECTIVE: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated. RESULTS: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR = 5.9, 95%CI: 1.7-19.8, p = 0.04). CONCLUSION: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.

Dietary glycemic index, glycemic load and risk of age-related cataract extraction: a case-control study in Italy.

PURPOSE: Although a role of glycemic index (GI) and glycemic load (GL) in age-related cataract development is plausible, a few studies, all conducted in USA or Australia, provided results on this issue. The aim of the present study was to provide new original data from a Mediterranean population. METHODS: We analyzed data from an Italian case-control study including 761 cases with cataract extraction and 1,522 hospital controls, frequency-matched with cases by center, sex, and age. Multivariate odds ratios (ORs) for GI and GL intakes were obtained from logistic regression models after allowance for major confounding factors, including non carbohydrate energy intake, smoking, and diabetes. RESULTS: The ORs of cataract extraction for the highest versus the lowest tertile were 1.20 (95% confidence interval, CI 0.91-1.57) for GI and 1.57 (95% CI 1.16-2.13) for GL, with a statistically significant trend in risk for GL (p < 0.01). Results were materially unchanged when diabetics were excluded from the analysis. No heterogeneity emerged across strata of sex, age, education, smoking habits and body mass index. CONCLUSIONS: The present study supports a positive association between dietary GL and the risk of cataract extraction, independently from diabetes, and a lack of association for GI.

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

BACKGROUND: Neoadjuvant Chemotherapy (NC) including trastuzumab induces a high rate of pathological Complete Responses (pCR) in patients with locally advanced HER2-overexpressing Breast Cancer (BC), but is penalized by a severe cardiotoxicity when combined with anthracyclines. A phase II study was designed to assess whether an anthracycline-free NC regimen based on the early addition of trastuzumab to paclitaxel may increase the pCR rate without inducing severe cardiotoxicity in patients with locally advanced HER2-overexpressing BC. Immunomonitoring was performed to assess the contribution of patients' immunological background to the induction of clinical responses. METHODS: Stage II-III HER2-positive BC patients received 24 weeks paclitaxel and trastuzumab NC, followed by 1 year adjuvant trastuzumab ± hormonal and/or radio-therapy. Assessment of pCR rate was the primary endpoint. A group of HER2-negative BC patients treated with neoadjuvant taxanes and anthracyclines was included. Serum levels of 10 cytokines and the efficiency of trastuzumab-mediated antibody-dependent cell cytotoxicity (ADCC) were monitored in vitro every 3 months. RESULTS: From July 2006 to February 2013, we enrolled 109 patients including 46 evaluable HER2-positive cases. A pCR rate of 50% was reached and no severe cardiotoxicity occurred. Serum cytokine profiling revealed only an IL-10 decrease (P = 0.02) in patients achieving a partial response, while HER2-negative patients disclosed marked cytokines changes. Compared to the unfavourable F/F genotype, patients carrying the V allele in the FcγRIIIa-158 polymorphism showed a higher efficacy of trastuzumab-ADCC throughout treatment (P ≤0.05). CONCLUSIONS: In the absence of anthracyclines, trastuzumab and paclitaxel induced a high rate of pCR, exploiting the synergy between the immunomodulating properties of these drugs and the retained immunological proficiency of patients with HER2-overexpressing BC. TRIAL REGISTRATION: Trial registration number: NCT02307227, registered on ClinicalTrials.gov (http://www.clinicaltrials.gov, November 26, 2014).

Time trends of cancer incidence in Setif, Algeria, 1986-2010: an observational study.

BACKGROUND: Incidence rates of various cancers are increasing in Arab countries and are expected to reach those of industrialized ones in few decades. This paper aimed to describe the incidence rates of most common cancers--and/or of those cancer preventable through modifiable behaviors--recorded in the province of Setif, Algeria from 1986 through 2010. METHODS: Cancer diagnoses for the 1986-2010 period were provided by the population-based Cancer Registry of Setif, disentangled by site, morphology, age (quinquennia), sex, and calendar period. The corresponding population was obtained from the Algerian Institute of Statistics. Age-standardized rates (world population) (ASR-WR) were computed by calendar period (five quinquennias from 1986-1990 to 2006-2010), while annual percent changes (APCs) were computed for the period 1996-2010. RESULTS: During the 2006-2010 period, ASR-WR for all cancer sites were 106.4/100,000 in men and 110.3 in women. The four leading cancers were: lung (18.0%); colon-rectum (9.6%); bladder (9.1%); and prostate (6.5%) in men; breast (36.4%); colon-rectum (8.5%); cervix uteri (6.0%); and thyroid (6.0%) in women. Between 1996-2010, overall cancer incidence increased statistically significantly (p < 0.05) in both men (APC = +2.5%) and women (APC = +3.7%). Statistically significant decreasing trends were observed for nasopharyngeal carcinoma (APC = -3.4%) in men, and for cervical (APC = -4.2%) and gallbladder (APC = -3.2%) cancers in women. Statistically significant increasing trends were observed for most common cancers both in men (lung:+1.8%, colon-rectum:+5.4%, prostate:+4.3%, liver:+8.9%, and bladder:+5.9%) and women (breast:+8.2%, colon-rectum:+4.5%, lung:+10.0%, liver:+5.4%, thyroid:+5.3%, and larynx:+13.8%). CONCLUSIONS: International recommendations against cancer must be strongly promoted in Setif after taking into account epidemiological transition, lifestyle, and environmental changes.

Early Onset of Lung Cancer in Small Areas as a Signature of Point Pollution Sources.

The impact of air pollution on lung cancer (LC) is difficult to detect in low-populated areas due to the potentially unfocused detection of pollutants and/or limited statistical power. This study identified and measured the harmful effect of pollution in small areas by considering the early onset of LC as a signature of pollution. This novel method requires a Bayesian standard curve calculated from the median age at LC onset and the corresponding median age of reference populations. Similar medians gathered from the area/s under investigation permits a probabilistic comparison with the standard curve. Statistically significant divergences can be interpreted as early or late LC onset. The method is exemplified in the Trieste municipality (northeast Italy) using data from the Friuli Venezia Giulia Cancer Registry (study population) and from the International Agency for Research on Cancer (reference population). Early LC onset has been observed near the pollution sources. Within 600 m of the iron foundry, onset ranged between 3.2 and 7.7 years earlier in men and between 11.7 and 16.8 years earlier in women. Near the shipyard, early onset was around 4 years in men and 7 years in women, while in the industrial area, early onset was 5 years in women only. Examining early LC onset may speed up the investigation of potential environmental hazards.

Fiber intake and risk of nasopharyngeal carcinoma: a case-control study.

Some studies examined the inverse relation between nasopharyngeal carcinoma (NPC) risk and dietary fibers in endemic populations. By means of a hospital-based case-control study, we verified whether this association was also present in Italy in connection with various types of dietary fibers. Cases were 198 patients with incident, histologically confirmed, NPC admitted to major teaching and general hospitals during 1992-2008. Controls were 594 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire including 78 foods, food groups, or dishes. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated for quartiles of intake of different types of fiber after allowance for energy intake and other potential confounding factors. Total fiber intake was inversely related to risk of NPC (OR = 0.58 for the highest vs. the lowest quartile of intake; 95% CI: 0.34-0.96). We found an inverse association for total soluble (OR = 0.58; 95% CI: 0.35-0.96) and total insoluble fiber (OR = 0.56; 95% CI: 0.33-0.95), in particular cellulose (OR = 0.57; 95% CI: 0.33-0.96), and lignin (OR = 0.51; 95% CI: 0.31-0.85). In conclusion, this study suggests that dietary intake of soluble and insoluble fibers is inversely related to NPC risk in a nonendemic southern population.

The use of PSA testing over more than 20 years: A population-based study in North-Eastern Italy.

OBJECTIVE: To describe the practice of prostate-specific antigen (PSA) testing over more than 20 years in Friuli Venezia Giulia (FVG), North-Eastern Italy. METHODS: A population-based, ecological study was conducted using information derived from regional administrative health-related databases. Data on PSA and prostate biopsies performed on resident men aged ⩾45 years from 1998 to 2019 were retrieved. PSA and biopsy rates were calculated as the number of men who had at least one such procedure in each calendar year over the mean resident male population of the same year. Temporal trends were analyzed using joinpoint regression (annual percentage change -APC). RESULTS: A total of 2,502,670 PSA were made between 1998 to 2019 in men aged ⩾45 years. The number of PSA steadily increased from 51,055 in 1998-1999 to 134,504 in 2010-2011, then dropped to 122,080 in 2018-2019. Significant changes in the slopes of PSA rates emerged in 2002 and 2009: the largest increase occurred during 1998-2002 (APC 18.4), followed by a smaller increase in 2002-2009 (APC 3.4) and a subsequent reduction (APC -2.5). Similar patterns emerged for all ages, but the decrease since 2009 was smaller for men aged ⩾65 years. An upward trend emerged in biopsy rate from 1998 to 2001 (APC 13.0), followed by a smaller increase until 2007 (APC 5.7) and a subsequent decrease. Biopsies as percentage of PSA decreased from 3.2% to 2.2%, particularly in those aged ⩾75 years. CONCLUSIONS: Although overall declining PSA rates have been observed in FVG since 2009, rates remained higher in the ⩾65-year-old group than in the 45-64-year-old group.

Breast cancer deaths attributable to alcohol consumption: Italy, 2015-2019.

A study was conducted to assess the fraction of female breast cancer (BC) deaths attributable to alcohol consumption in Italy. National mortality data for the period 2015-2019 were used along with national estimates of women from the general population exposed to moderate (11-20 gr/day) or heavy (>20 gr/day) alcohol consumption. From 2015 to 2019, 2918 (4.6%) out of 63,428 BC| deaths were attributable to alcohol consumption, including 1269 deaths (2.0%) caused by moderate consumption. Study findings could help stakeholders to prioritize programs aimed at reducing alcohol consumption, and to improve ways to effectively communicate alcohol-related health risks, including moderate consumption.

Comparison between two cancer registry quality check systems: functional features and differences in an Italian network of cancer registries dataset.

Purpose: The aim of this study was to compare the functional characteristics of two computer-based systems for quality control of cancer registry data through analysis of their output differences. Methods: The study used cancer incidence data from 22 of the 49 registries of the Italian Network of Cancer Registries registered between 1986 and 2017. Two different data checking systems developed by the WHO International Agency for Research on Cancer (IARC) and the Joint Research Center (JRC) with the European Network of Cancer Registries (ENCR) and routinely used by registrars were used to check the quality of the data. The outputs generated by the two systems on the same dataset of each registry were analyzed and compared. Results: The study included a total of 1,305,689 cancer cases. The overall quality of the dataset was high, with 86% (81.7-94.1) microscopically verified cases and only 1.3% (0.03-3.06) cases with a diagnosis by death certificate only. The two check systems identified a low percentage of errors (JRC-ENCR 0.17% and IARC 0.003%) and about the same proportion of warnings (JRC-ENCR 2.79% and IARC 2.42%) in the dataset. Forty-two cases (2% of errors) and 7067 cases (11.5% of warnings) were identified by both systems in equivalent categories. 11.7% of warnings related to TNM staging were identified by the JRC-ENCR system only. The IARC system identified mainly incorrect combination of tumor grade and morphology (72.5% of warnings). Conclusion: Both systems apply checks on a common set of variables, but some variables are checked by only one of the systems (for example, checks on patient follow-up and tumor stage at diagnosis are included by the JRC-ENCR system only). Most errors and warnings were categorized differently by the two systems, but usually described the same issues, with warnings related to "morphology" (JRC-ENCR) and "histology" (IARC) being the most frequent. It is important to find the right balance between the need to maintain high standards of data quality and the workability of such systems in the daily routine of the cancer registry.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.