ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Sindrome dell'ovaio policistico: ruolo dell'obesità ed impatto sulla qualità di vita

La Sindrome dell’Ovaio Policistico (Pcos) è disordine non esclusivamente riproduttivo ma sistemico, con importanti implicazioni metaboliche. Nelle adolescenti affette da Pcos sono molto frequenti oligomenorrea, irsutismo ed obesità; in età riproduttiva, infertilità e, in fase climiterica, obesità, dislipidemia, intolleranza ai carboidrati e franco diabete mellito. Le donne con Pcos possono presentare gradi diversi di Insulino-resistenza (IR), che contribuiscono all’aumentato rischio di Sindrome Metabolica. L’attività svolta dalla dottoranda ha messo in evidenza che l’obesità, soprattutto quella addominale, oltre ad essere una manifestazione quasi ineluttabilmente legata al decorso della Pcos come effetto dell’iperandrogenismo, potrebbe avere un ruolo patogenetico importante nello sviluppo e nella progressione della sindrome in donne suscettibili. In linea con i dati emergenti dalla letteratura, lo studio evidenzia importanti differenze dei parametri ormonali e metabolici tra donne con IMC superiore e donne con IMC inferiore a 25, le più rilevanti delle quali risultano la più spiccata insulino-resistenza e la più severa iperinsulinemia nelle donne in sovrappeso od obese. Questo dato emerge dalla significatività della correlazione di Pearson tra IMC e ciascuno degli indici scelti per la valutazione della sensibilità all’Insulina (Insulinemia a digiuno, G/I ratio, Homa-IR, Homa % B, Tg/HDL, e CT/HDL). Il dato rafforzerebbe l’ipotesi, postulata dalla maggior parte degli studiosi, che l’insulino-resistenza nell’obesità é provocata da meccanismi indipendenti da quelli che sono responsabili della Pcos. L’obesità, quindi, aggraverebbe uno stato di ridotta sensibilità all’Insulina, presente nella Pcos indipendentemente dall’ IMC. A conferma di ciò i dati dello studio svolto evidenziano una differenza significativa nei livelli di Insulina, Homa-IR e Homa % B tra la popolazione con Pcos, indipendentemente dall’ IMC, e quella di controllo. Rispetto ai controlli le pazienti con Pcos reclutate hanno maggiori livelli di Testosterone totale e il coefficiente di Pearson tra IMC e Testosterone totale, evidenzia un più grave stato iperandrogenico nelle pazienti obese, rispetto alle non obese. Significativa anche la correlazione tra IMC e circonferenza vita. Ben il 74% delle donne con IMC>25 mostra un’obesità a distribuzione androide (circonferenza vita >88 cm). Le donne con Pcos e IMC>25 presentano anche un profilo lipidemico più aterogeno, con una correlazione positiva tra IMC e Trigliceridi e IMC e Colesterolo LDL e una correlazione negativa tra IMC e Colesterolo HDL. Questo dato, confermato anche da altri studi, renderebbe conto della maggiore predisposizione delle donne con Pcos e IMC elevato allo sviluppo di complicanze cardiovascolari a lungo termine. Per quanto riguarda la Glicemia, non sono emersi né importanti differenze con la popolazione generale, verosimilmente a causa della giovane età del campione, né una correlazione significativa con l’ IMC. Quanto al fenotipo clinico, infine, emerge una evidente correlazione tra IMC irsutismo, acne e seborrea. Se ne conclude che, per quanto l’obesità, aggravando lo stato di insulino-resistenza e di iperandrogenismo, contribuisca a peggiorare il fenotipo clinico e i parametri metabolici delle donne con Pcos, configurandosi a tutti gli effetti come uno dei fattori principali nel complesso meccanismo patogenetico alla base di questa endocrinopatia, essa non costituisce il solo determinante della Sindrome Metabolica nelle donne con Pcos. Sarebbe, pertanto, un fattore di confondimento, che non consentirebbe di valutare il contributo, pure importante, di altri fattori, tra cui durata dell’obesità, insulino-resistenza, presente nella Pcos indipendentemente dal IMC, fattori di rischio metabolico individuali, etnia, predisposizione genetica, familiarità e, soprattutto, età. È ovvio che la Pcos, soprattutto se associata alla obesità, sia causa di un severo distress, soprattutto nelle pazienti più giovani, che devono far fronte ai disagi fisici e psicologici che può comportare. Numerosi studi hanno valutato l’impatto della Pcos sulla qualità di vita usando strumenti standardizzati. Di quelli degni di nota, 12 hanno fatto ricorso a strumenti di valutazione generica (9 di essi, l’SF 36) e 8 hanno usato uno strumento specifico, lo PCOSQ. Tuttavia, poiché nessuno di essi è stato condotto in Italia, la seguente ricerca si configura come una novità nel panorama letterario nazionale. In particolare è stata valutato l’impatto negativo della Pcos sulla qualità della vita tramite l’utilizzo di questionari sia generici che specifici. Un’attenzione particolare è stata rivolta a confermare se e in che misura l’obesità contribuisce a compromettere, di per sé, la qualità di vita. I disturbi e i disagi psicologici, stigmatizzati con il questionario SCL-90-R, influenzano fortemente il benessere globale e il campione di donne con Pcos, soprattutto la subpopolazione con IMC>25, ha mostrato, rispetto alla popolazione di controllo, valori significativamente elevati di tutti e tre gli indici globali. Particolarmente compromesse risultano, indipendentemente dal IMC, le dimensioni sintomatiche Ossessione-Compulsione, Depressione e risulta compromessa anche la dimensione Ansia. Dall’analisi dei risultati dello PCOSQ emerge, conformemente alla letteratura, un più frequente interessamento del dominio peso (22%), seguito dall’ irsutismo (19%). Gli altri domini compromessi sono: emozioni e acne, con il 18% e, infertilità e problemi mestruali, con il 17% . In conclusione i risultati ottenuti confermano che nelle donne con Pcos la Sindrome Metabolica o, in alternativa, fattori di rischio metabolico individuale, possono essere presenti con frequenza maggiore rispetto alla popolazione femminile generale e suggeriscono anche che la Sindrome Metabolica possa avere un esordio significativamente più precoce. L’insieme dei dati rivoluzionerebbe il concetto di Pcos come disordine squisitamente riproduttivo e ne enfatizzerebbe il carattere metabolico. D’altra parte, visto che la Pcos, per le sue implicazioni fisiche e metaboliche, rappresenta una importante fonte di distress psichico, sarebbe sempre opportuno associare, all’esame clinico, uno screening psicologico che valuti il fragile equilibrio di queste pazienti, avvalendosi di misure della qualità di vita e della qualità di vita in relazione alla salute. Un ulteriore aspetto indagato dal seguente studio è stato quello di valutare gli effetti di un regime dietetico moderatamente iperlipidico o normolipidico sulle manifestazioni cliniche , sui parametri ormonali e metabolici di tale sindrome. Attualmente sono state reclutate 9 pz, che dopo un’indagine clinica e bioumorale sono state sottoposte in maniera random ad un regime dietetico moderatamente iperlipidico (lipidi 40%, proteine 15%, carboidrati 45%) o a una dieta normolipidica (lipidi 30%, proteine 15%, carboidrati 55%) per 3 mesi. Successivamente dopo una rivalutazione laboratoristica hanno praticato dieta normolipidica o moderatamente iperlipidica per altri 3 mesi, e infine un ulteriore controllo clinico e bioumorale. Da un’analisi dei dati preliminari sembrerebbe che un regime dietetico moderatamente iperlipidico agendo sull’insulino-resistenza, sarebbe utile nel migliorare il profilo metabolico-ormonale delle pazienti con PCOS, soprattutto se sovrappeso od obese. Al momento i dati preliminari sono incoraggianti, per cui è opportuno continuare questo studio per consolidare i risultati ottenuti

Resveratrol improves the lipid profile promoted by red yeast rice (monacolin k) in patients with moderate dyslipidemia: An open-label, randomized, parallel-group controlled clinical trial

Abstract Introduction: A relevant role is now emerging for nutraceuticals and specific functional foods in the treatment of dyslipidemia. The aim of this study was to evaluate the efficacy of a nutraceutical multi-target approach in subjects with moderate cardiovascular risk and to compare it with red yeast rice (RYR) treatment alone. Materials and Methods: Sixty patients with a first diagnosis of moderate dyslipidemia were included in a 6-week open-label, randomized, parallel-group controlled clinical trial and were treated with a nutraceutical supplement of Red Yeast Rice (RYR) extract containing 10 mg of monacolin k or its combination with 48 mg of an improved form of highly bioavailable resveratrol. The dosage of RYR was selected on the basis of its expected efficacy in reducing low-density lipoprotein- cholesterol also approved by the EFSA panel. All differences were assessed by Student's t test with P values .05 are considered as statistically significant. Statistical analysis was performed by using Excel. Results: Treatment with RYR (10 mg monacolin K) led to a reduction of total cholesterol (20%) and low-density lipoprotein- cholesterol (21%). The combination with resveratrol however, compared to RYR alone significantly reduced triglyceride (-18 %) levels, systolic blood pressure (-2 %) and HOMA index (-17 %). Discussion: These results indicate that the nutraceutical supplementation of RYR associated with resveratrol not only shows lipid-lowering activity but compared to RYR treatment alone significantly also ameliorates other metabolic parameters. Thus, may represent a valid and safe approach, especially in people with moderate cardiovascular risk, in which a pharmacologic intervention may not be appropriate

Teriparatide vs. alendronate as a treatment for osteoporosis: Changes in biochemical markers of bone turnover, BMD and quality of life

BACKGROUND: We studied the use of teriparatide in postmenopausal women with severe osteoporosis. MATERIAL/METHODS: Two groups (A and B) of patients affected by severe osteoporosis (T-score ⩽−2.5 at bone mineral density were analyzed and 2 vertebral fractures on radiograph). Group A was treated for 18 months with 20 μg/day of teriparatide. Group B was treated with bisphosphonates 70 mg/week. Every woman assumed 1 g of calcium and 800 IU of vitamin D3 daily. We evaluated the effects of therapy after 18 months (T18) from the beginning with bone turnover markers (alkaline phosphatase, procollagen type 1 N-terminal propeptide, and N-telopeptide cross-links) and dual-energy X-ray absorptiometry. RESULTS: Group A, at T18 procollagen type 1 N-terminal propeptide levels, increased 127%; bone alkaline phosphatase levels increased to 65%; N-telopeptide cross-links levels increased to 110%. Group B, at T18 procollagen type 1 N-terminal propeptide levels, decreased to 74%; bone alkaline phosphatase levels decreased to 41%; N-telopeptide cross-links levels decreased to 72%. After 18 months, lumbar bone mineral density increased to 12.4% and femoral bone mineral density increased to 5.2% in group A. Group B lumbar bone mineral density increased to 3.85% and femoral bone mineral density increased to 1.99%. Only a new vertebral fracture occurred in group A (2.4%), whereas 6 fractures occurred in group B (15.7%). The quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO) revealed a significant improvement in daily living, performed domestic jobs, and locomotor function in groups A and B. CONCLUSIONS: The use of rhPTH in patients with severe osteoporosis offers more protection against fractures and improves the QoL more than bisphosphonates

The risk of osteoporosis in patients with liver cirrhosis: A meta-analysis of literature studies

Objective Data about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta-analysis of literature studies on this topic. Design MEDLINE, Cochrane library, EMBASE, Scopus and Web of Science databases have been searched to retrieve all articles of interest. Data on prevalence of osteoporosis, bone mineral density (BMD) and bone turnover laboratory parameters were compared among cirrhotic patients and control subjects without cirrhosis. Patients Studies on patients with liver cirrhosis screened for the presence of osteoporosis were included. Results Six case-control studies (372 cirrhotic patients and 1579 controls) were included. The prevalence of osteoporosis was higher in cirrhotic patients than in controls (34·7% vs 12·8%, OR: 2·52, 95%CI: 1·11, 5·69; P = 0·03, I2 = 81%; P = 0·005). Accordingly, a reduced lumbar spine BMD (MD: -0·13, 95%CI: -0·24, -0·02; P = 0·02, I2 = 93%; P < 0·00001) and z-score (MD: -1·06, 95%CI: -1·79, -0·34; P = 0·004, I2 = 95%; P < 0·00001) were found in cirrhotic patients as compared with controls. In contrast, no significant differences were reported in femoral neck BMD and z-score. Interestingly, bone turnover laboratory parameters widely confirmed these results showing higher levels of ALP and D-Pyr, accompanied by reduced levels of IGF-1, PTH and 25-OH-D in cirrhotic patients as compared with controls. Conclusions Despite the high heterogeneity among studies, data showed an increased prevalence of osteoporosis in patients with cirrhosis. This information suggests the need of an accurate screening of bone mineral density in patients with liver cirrhosis to plan an adequate osteoporosis managemen

Quality of life in overweight (obese) and normal-weight women with polycystic ovary syndrome

Objective: Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are over­weight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients’ quality of life and to what extent obesity contributes to worsen this disease. Design: To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) &gt; 25 kg/m2 (group A1) and 50 with BMI &lt; 25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). Results: Our results showed a considerable worsening of HRQoL in PCOS patients (A) com­pared with controls (B). In addition, patients with PCOS and BMI &gt; 25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion: PCOS is a complex disease that alone determines a deterioration of HRQoL. The inno­vative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress

Quality of life in overweight (Obese) and normal-weight women with polycystic ovary syndrome

Objective: Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are over­weight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients’ quality of life and to what extent obesity contributes to worsen this disease. Design: To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) &gt; 25 kg/m2 (group A1) and 50 with BMI &lt; 25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). Results: Our results showed a considerable worsening of HRQoL in PCOS patients (A) com­pared with controls (B). In addition, patients with PCOS and BMI &gt; 25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion: PCOS is a complex disease that alone determines a deterioration of HRQoL. The inno­vative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress