AIM: To present a summary of the updated guidelines of the Italian Prostate Biopsies Group following the best recent evidence of the literature.
MATERIALS AND METHODS: A systematic review of the new data emerging from 2012-2015 was performed by a panel of 14 selected Italian experts in urology, pathology and radiology. The experts collected articles published in the English-language literature by performing a search using Medline, EMBASE and the Cochrane Library database. The articles were evaluated using a systematic weighting and grading of the level of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation framework system.
RESULTS: An initial prostate biopsy is strongly recommended when i) prostate specific antigen (PSA) >10 ng/ml, ii) digital rectal examination is abnormal, iii) multiparametric magnetic resonance imaging (mpMRI) has a Prostate Imaging Reporting and Data System (PIRADS) ≥4, even if it is not recommended. The use of mpMRI is strongly recommended only in patients with previous negative biopsy. At least 12 cores should be taken in each patient plus targeted (fusion or cognitive) biopsies of suspicious area (at mpMRI or transrectal ultrasound). Saturation biopsies are optional in all settings. The optimal strategy for reducing infection complications is still a controversial topic and the instruments to reduce them are actually weak. The adoption of Gleason grade groups in adjunction to the Gleason score when reporting prostate biopsy results is advisable.
CONCLUSION: These updated guidelines and recommendations are intended to assist physicians and patients in the decision-making regarding when and how to perform a prostatic biopsy.

Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.

 Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis.
AIM: To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center.
MATERIAL AND METHODS: Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively.
RESULTS: Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027).
CONCLUSIONS: This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.

Lung cancer is still considered a big killer among cancer diseases, due to high incidence and mortality rates. The newer frontiers of therapeutic development regard the discovery of oncogene driven tumours: however, the majority of NSCLC patients are wild type and they cannot be treated with targeted based agents. The recent positive results obtained with immunotherapy and with the combination of angiogenesis inhibitors and docetaxel, changed the therapeutic scenario of the second line therapy of non squamous NSCLC without actionable mutations. A major issue is currently the lack of predictive biomarkers that could help the oncologists in the choice of the best second-line treatment. Aim of this project was to define an optimal therapeutic pathway for patients with non-squamous NSCLC, through a working group of a large number of Italian lung cancer oncologists. Panellists have identified and discussed the more significant criteria in the second-line setting for a therapeutic decision between the combination of angiogenesis inhibitors plus chemotherapy or immunotherapy. Finally, they expressed their preference on each criterion, building a proposal of a decision-making tree for a second-line treatment of non-squamous NSCLC.

Although the public should have complete and correct information about risk/benefit ratio of breast cancer screening, public knowledge appears generally scarce and oriented to overestimate benefits, with little awareness of possible disadvantages of the screening.We evaluated any document specifically addressed to the general female public and posted on internet by Italian public health services. The presence of false positive, false positive after biopsy, false negative, interval cancer, overdiagnosis, lead-time bias, exposure to irradiation, and mortality reduction was analyzed.Of the 255 websites consulted, 136 (53.3%) had sites addressed to the female public. The most commonly reported information points were the false-positive (30.8% of sites) and radiation exposure (29.4%) rates. Only 11 documents mentioned overdiagnosis, 2 mentioned risk of false positive with biopsy, and only 1 mentioned lead-time bias. Moreover, only 15 sites (11.0%) reported quantitative data for any risk variables.Most documents about breast cancer screening published on the web for the female public contained little or no information about risk/benefit ratio and were biased in favor of screening.

Lycium barbarum is a famous plant in the traditional Chinese medicine. The plant is known to have health-promoting bioactive components. The properties of Lycium barbarum berries cultivated in Umbria (Italy) and their effect on human hepatocellular carcinoma cells (HepG2) have been investigated in this work. The obtained results demonstrated that the Lycium barbarum berries from Umbria region display high antioxidant properties evaluated by total phenolic content and ORAC method, on hydrophilic and lipophilic fractions. Moreover, on HepG2 cell line Lycium barbarum berries extract did not change cell viability analyzed by MTT and Trypan blue exclusion assay and did not induce genotoxic effect analyzed by comet assay. Furthermore, it was demonstrated, for the first time, that the berries extract showed a protective effect on DNA damage, expressed as antigenotoxic activity in vitro. Finally, Lycium barbarum berries extract was able to modulate the expression of genes involved in oxidative stress, proliferation, apoptosis, and cancer. In particular, downexpression of genes involved in tumor migration and invasion (CCL5), in increased risk of metastasis and antiapoptotic signal (DUSP1), and in carcinogenesis (GPx-3 and PTGS1), together with overexpression of tumor suppressor gene (MT3), suggested that Umbrian Lycium barbarum berries could play a protective role against hepatocellular carcinoma.

BACKGROUND: Capsular contracture (CC) is a major complication of breast surgery with smooth and textured implants. Polyurethane (PU) foam-coated breast implants were developed to decrease the incidence of CC.
OBJECTIVES: The authors determined the incidence of CC following 2-stage breast reconstruction using PU foam-covered implants, with and without radiation therapy.
METHODS: The records of 92 patients who received 115 PU implants were retrospectively reviewed. The rates of CC over time were compared for irradiated and nonirradiated groups with a Kaplan-Meier analysis and log-rank test. CC rates also were analyzed with respect to age.
RESULTS: The median follow-up time for patients was 103.3 months. Nine patients experienced unilateral Baker grade III or IV fibrous CC, including 6 patients from the irradiated group and 3 patients from the nonirradiated group. The overall cumulative incidence of CC at 9 years was 8.1%. In the irradiated and nonirradiated groups, the 9-year cumulative incidence was 10.7% and 5.5%, respectively. CC occurred within 3 years in the irradiated group and within 7 years in the nonirradiated group. The incidence of CC appeared to be higher among younger patients.
CONCLUSIONS: Radiation therapy increases the risk of high-grade CC with textured or smooth implants. PU implants are associated with a much lower cumulative incidence of CC following 2-stage breast reconstruction, even when radiotherapy is performed. LEVEL OF EVIDENCE 3.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with a lower cancer risk, possibly via a reduction of mutagenic oxygen-free radicals and by reducing nicotinamide-adeninedinucleotide-phosphate for replicating cells. In Sardinia, the enzyme defect is frequent as a consequence of selection by malaria in the past. This study investigated the relationship between G6PD deficiency and colorectal cancer (CRC).A retrospective case-control study of 3901 patients from Sardinia, who underwent a colonoscopy between 2006 and 2016, was performed. G6PD phenotype was assessed for each subject. The proportion of pre and malignant colorectal lesions was compared in cases (G6PD-deficient) and controls (G6PD-normal). Data concerning age, sex, family history of CRC, smoking habits, body height, and weight, and also associated diseases were collected.The CRC risk reduction was 43.2% among G6PD-deficient compared with G6PD-normal subjects (odds ratio 0.57, 95% confidence interval 0.37-0.87, P = 0.010). Age, sex, family history of CRC, and also comorbidities such as type 1 diabetes and ischemic heart disease, were significantly associated with CRC risk. The protective effect of G6PD deficiency remained significant after adjusting for all covariates by logistic regression analysis, and was consistently lower across all age groups.Glucose-6-phosphate dehydrogenase enzyme deficiency is associated with a reduced risk of CRC.

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using "American College of Medical Genetics and Genomics" guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.

As part of the third Mediterranean Symposium in Thoracic Surgical Oncology, we introduce the Italian VATS Group ( http://vatsgroup.org/sito/index.php ). This national collaborative initiative was established in 2013 and started to recruit patients in January 2014; as of July 2016, 3680 patients have been enrolled in the database. Three different video-assisted thoracic surgery approaches have been predominantly used by Italian thoracic surgery centers, 71% of them preferentially adopting a multi-portal approach, with a 20% recorded morbidity. The majority of the cases were stage I adenocarcinomas of the lung. Conversion to open surgery occurred in 9% of the cases. The study suggests video-assisted thoracic surgery lobectomy as a 'gold standard' for the surgical treatment of early-stage lung cancer in Italy.

Incidence of neuroepithelial Primary Brain Tumors (nPBT) varies, ranging from 7.3 to 11.6 cases/100,000/year across Europe. We present incidence and survival of nPBT in the Emilia-Romagna region (ER), Italy. This study is the largest in Southern Europe. Specialists in neurosurgery, neurology, neuroradiology, oncology, radiotherapy, genetics, and pathology of ER notified all suspected nPBT adult cases residing in ER (4,337,966 inhabitants) observed during 2009. Furthermore, through ICD-9 discharge codes, we identified and reviewed all possible cases. Neuroepithelial PBT diagnosis was based on histological or radiological findings. We included 400 incident nPBT cases, of which 102 (25%) were retrospectively identified. These latter were significantly older. The standardized incidence was 10.5/100,000/year (95% CI 9.4-11.5), higher for men. It was 9.2/100,000/year (95% CI 8.3-10.2) for astrocytic tumors, 0.6/100,000/year (95% CI 0.4-0.9) for oligodendroglial tumors, and 7.1 (95% CI 6.3-8.0) for glioblastoma (GBM). Among GBM patients, median survival was 249 days if prospectively identified vs. 132 days when identified through ICD-9 codes (p < 0.0001). The incidence of nPBT in the ER region is among the highest in the literature. Older patients were more likely to escape an active surveillance system. This should be considered when comparing incidence rates across studies, giving the increasing number of elderly people in the general population.

Multiresistant bacterial infections are a potentially life-threatening condition in acute leukaemia (AL) patients. We aimed to better define the very recent epidemiology and outcome of bloodstream infections (BSIs) in a real-life setting. We prospectively collected all consecutive febrile/infectious episodes occurring in AL patients admitted to 9 haematology units. In 293 AL patients, 433 BSIs were diagnosed. Gram-positive (GP) bacteria were isolated in 44.8 % BSI and Gram-negative (GN) in 38.3 %, while polymicrobial aetiology- or fungi-related events were identified in 15.7 and 1.1 % of the cases, respectively. GP was observed more frequently in patients not in complete remission (p = 0.04), while GN during consolidation cycles (p = 0.003). Extended spectrum β-lactamase-producing strains accounted for 23.2 % of enterobacteria. They were associated with previous antibiotic exposure, including fluoroquinolones prophylaxis (p = 0.01). Carbapenem-resistant (CR) strains occurred in 9 % of enterobacteria. Among Pseudomonas aeruginosa strains, 21.6 % were multiresistant. Overall 30-day mortality was 8.5 %. CR GN and multiresistant P. aeruginosa BSIs were independent predictors of death (p = 0.002), as well as relapsed/resistant AL (18.3 %; p = 0.0002) and the presence of pulmonary infiltrates (26.6 %; p < 0.001). Although GP still predominate over GN BSI, the percentage of antibiotic resistant GN strains is considerable in AL patients and it is associated with poor prognosis.

Cancer care involves many ethical issues. The need for more patient-centered healthcare together with the improved empowerment of every person diagnosed with cancer have been transposed by the Italian Association of Medical Oncology (AIOM) and eventually translated in the Ragusa statement. This position paper describes the philosophy that lies beneath this document and its fundamental principles.

PURPOSE: Solid-organ tumor incidences are higher in solid organ transplant patients than in the general population. The aim of this study was to analyze solid-organ tumor frequency and characteristics in a population of lung transplant patients and provide a brief review of the literature.
METHODS: A retrospective analysis was conducted of all patients who underwent a lung transplant in the Lung Transplant Program at the University Hospital of Siena, Italy, from 2001 to 2014 (n = 119). Patients' demographics, pretransplant characteristics, immunosuppressive therapy, and infectious factors were recorded.
RESULTS: Nine patients with a median age of 59.0 years (range 50-63) of our cohort developed a solid-organ tumor (7.5%). Most of the patients experienced nonmelanoma skin cancer (44.4%); the others were diagnosed with lung cancer (22.2%), breast cancer (22.2%), and colon-rectal cancer (11.2%). The median time from transplantation to tumor diagnosis was 895.0 days (range 321-2046). No differences in pretransplant characteristics, immunosuppressive therapy, or infectious factors were found between patients who developed solid organ tumors and those who did not.
CONCLUSIONS: The present study confirmed that de novo malignancies are a major issue in lung transplant patients; in particular, skin and lung cancers demonstrated a higher incidence rate. Oncologic treatment of these patients is complex, requiring close collaboration between the transplant team and oncologist. Strict screening programs are key factors for an early diagnosis and to allow for prompt treatment resulting in a better outcome.

INTRODUCTION: Despite the preference of many patients to die at home, high proportions of patients with advanced cancer undergo major procedures, receive intensive care, and die in the hospital. The goal of this study is to examine variation in hospital utilization and site of death for patients dying with poor-prognosis cancer in the Regione Emilia-Romagna (RER), Italy.
METHODS: We conducted a retrospective, population-level study using administrative data. Patients were included if they died in 2012 and had at least one hospital admission for metastatic or poor-prognosis cancer within 180 days of death. Variations in the use of the hospital, intensive care, and procedures performed were evaluated.
RESULTS: 11,470 patients died with metastatic or poor-prognosis cancer in 2012. Seventy-eight percent of patients were hospitalized in the last month of life while 50.7% of patients died in the hospital. Results varied by local health authority from 38.3% to 69.3%. Of patients who had an ICU stay, 55.1% in the community hospitals and 59.8% in the teaching hospitals were admitted to the ICU on the day of death or the day before death. 7.5% of patients underwent a major procedure in the last 30 days of life.
CONCLUSIONS: The overall high rate, and substantial variation, in hospital care at the end of life offers the RER the opportunity to evaluate if increasing availability of palliative care, along with provider and patient education, could reduce utilization of high-cost hospital care and increase patient and family satisfaction.

INTRODUCTION: The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the outcome of HIV-infected patients by prolonging their survival. The increase in life expectancy has led to an increased risk of non-AIDS-related mortality and morbidity, including cardiovascular diseases, neurocognitive diseases, neuroendocrine dysfunctions and cancer. Areas covered: The GICAT (Italian Cooperation Group on AIDS and Tumors) has demonstrated that patients who receive a multidisciplinary approach with the combination of anticancer agents (AC) and HAART can achieve better responses and survival rates than patients who receive AC alone. The first obstacle for the oncologist to plan treatment for cancer HIV-patients is the preliminary evaluation of drug-drug interactions between AC and HAART. Recent progress in pharmacogenomics could provide a new approach for personalized treatments. The rationale of this review is to summarize the existing data on the impact of HAART on the clinical management of cancer patients with HIV/AIDS and DDIs between antiretrovirals and AC. In addition, to maximize the efficacy of both concomitant therapy and to minimize the risk of DDIs, a currently useful list of pharmacogenomic markers of key metabolic enzymes is provided. Expert opinion: In this scenario, the importance of cooperation between oncologists and other health specialists (i.e., infectivologists, pharmacists, genetics and lab specialists) must not be underestimated in the management of these patients with the aim of planning an individual treatment strategy.

BACKGROUND AND AIMS: Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is frequently challenging. We describe a large series of patients with p-NETs in whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography (EUS) were performed.
METHODS: This was a retrospective analysis of prospectively collected sporadic p-NET cases. All patients underwent both standard multidetector CT study and EUS with fine-needle aspiration (FNA). The final histological diagnosis was achieved on a post-surgical specimen. Chromogranin A (CgA) levels were measured.
RESULTS: A total of 80 patients (mean age: 58 +/- 14.2 years; males: 42) were enrolled. The diameter of functioning was significantly lower than that of non-functioning p-NETs (11.2 +/- 8.5 mm vs 19.8 +/- 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non-functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall, the CT study detected the lesion in 51 (63.7%) cases, being negative in 26 (68.4%) patients with a tumor CONCLUSIONS: Data of this large case series would suggest that the EUS should be included in the diagnostic work-up in all patients with a suspected p-NET, even when the CT study was negative for a primary lesion in the pancreas.

BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been reported to be associated with an increased risk of developing extra-pancreatic malignancies. A common genetic background has been hypothesised to be responsible for such an association. Human chromosomal region 8q24 has been associated with many types of cancer. The majority of these associations lie at approximately 128 Mb on chromosome 8. We conducted a study in order to examine the association between IPMN and single nucleotide polymorphisms (SNPs) from the 8q24 region, namely rs10505477, rs6983267, rs7014346, rs6993464, previously reported to influence general cancer susceptibility.
METHODS: The study was performed on 117 IPMN cases and 231 controls. Cases were enrolled at the Digestive Endoscopy Unit, Policlinico Agostino Gemelli from January, 2010 to June, 2011, with either a prevalent or incident IPMN diagnosis. Status of SNPs was determined using a StepOne Real-time PCR system (Applied Biosystems) and TaqMan SNP Genotyping Assay™ 40X. Unconditional multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for the association of selected SNPs and IPMNs.
RESULTS: Cases were more likely to report a 1st degree family history of cancer (p<0.001), as well as heavy smoking (p=0.001) and heavy drinking habits (p<0.001). No significant association was observed between IPMN and selected SNPs. The results were confirmed also when stratified according to any 1st-degree family history of cancer.
CONCLUSION: Patients with IPMN do not have a higher prevalence of SNPs in the human chromosomal region 8q24 in respect to the control population.

Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

PURPOSE: The histological response to neoadjuvant chemotherapy is an important prognostic factor in patients with osteosarcoma (OS) and Ewing sarcoma (EWS). The aim of this study was to assess baseline primary tumour FDG uptake on PET/CT, and serum values of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), to establish whether these factors are correlated with tumour necrosis and prognosis.
METHODS: Patients treated between 2009 and 2014 for localized EWS and OS, who underwent FDG PET/CT as part of their staging work-up, were included. The relationships between primary tumour SUVmax at baseline (SUV1), SUVmax after induction chemotherapy (SUV2), metabolic response calculated as [(SUV1 - SUV2)/SUV1)] × 100, LDH and ALP and tumour response/survival were analysed. A good response (GR) was defined as tumour necrosis >90 % in patients with OS, and grade II-III Picci necrosis (persitence of microscopic foci only or no viable tumor) in patients with Ewing sarcoma.
RESULTS: The study included 77 patients, 45 with EWS and 32 with OS. A good histological response was achieved in 53 % of EWS patients, and 41 % of OS patients. The 3-year event-free survival (EFS) was 57 % in EWS patients and 48 % OS patients. The median SUV1 was 5.6 (range 0 - 17) in EWS patients and 7.9 (range 0 - 24) in OS patients (p = 0.006). In EWS patients the GR rate was 30 % in those with a high SUV1 (≥6) and 72 % in those with a lower SUV1 (p = 0.0004), and in OS patients the GR rate was 29 % in those with SUV1 ≥6 and 64 % in those with a lower SUV1 (p = 0.05). In the univariate analysis the 3-year EFS was significantly better in patients with a low ALP level (59 %) than in those with a high ALP level (22 %, p = 0.02) and in patients with a low LDH level (62 %) than in those with a high LDH level (37 %, p = 0.004). In EWS patients the 3-year EFS was 37 % in those with a high SUV1 and 75 % in those with a low SUV1 (p = 0.004), and in OS patients the 3-year EFS was 32 % in those with a high SUV1 and 66 % in those with a low SUV1 (p = 0.1). Histology, age and gender were not associated with survival. In the multivariate analysis, SUV1 was the only independent pretreatment prognostic factor to retain statistical significance (p = 0.017). SUV2 was assessed in 25 EWS patients: the median SUV2 was 1.9 (range 1 - 8). The GR rate was 20 % in patients with a high SUV2, and 67 % in those with a low SUV2 (p = 0.02). A good metabolic response (SUV reduction of ≥55 %) was associated with a 3-year EFS of 80 % and a poor metabolic response with a 3-year EFS of 20 % (p = 0.05). In the OS patients the median SUV2 was 2.7 (range 0 - 4.5). Neither SUV2 nor the metabolic response was associated with outcome in OS patients.
CONCLUSION: FDG PET/CT is a useful and noninvasive tool for identifying patients who are more likely to be resistant to chemotherapy. If this finding is confirmed in a larger series, SUV1, SUV2 and metabolic response could be proposed as factors for stratifying EWS patients to identify those with high-grade localized bone EWS who would benefit from risk-adapted induction chemotherapy.

AIM: The present survey investigates the views of medical oncologists, general practitioners (GPs) and patients about the various surveillance strategies.
METHODS: An online survey was conducted in Italy on a population of 329 medical oncologists, 380 GPs and 350 patients.
RESULTS: Most of GPs (n = 291; 76%) claim that follow-up should be provided by the collaboration between GPs and medical oncologists. Most medical oncologists report to have a poor relationship with GPs (n = 151; 46%) or no relationships at all (n = 14; 4%). Most patients believe there is no real collaboration between medical oncologists and GPs (n = 138; 54%).
CONCLUSION: GPs, medical oncologists and patients share the idea that the collaboration between oncologists and GPs for surveillance of cancer survivors is poor and should be improved.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

The use of imaging to maximize precision and accuracy throughout the entire process of radiation therapy (RT) delivery has been called "Image-guided RT" (IGRT). RT has long been image guided: in fact, historically, the portal films and later electronic megavoltage images represented an early form of IGRT. A broad range of IGRT modalities is now available and adopted. The target location may be defined for each treatment fraction by several methods by localizing surrogates, including implanted fiducial markers, external surface markers or anatomical features (through planar imaging, fluoroscopy, KV or MV computed tomography, magnetic resonance imaging, ultrasound and X-ray imaging, electromagnetic localization, optical surface imaging, etc.). The aim of the present review is to define practical recommendations for IGRT.

AIMS: This study was designed to answer the question whether surgery due to newly diagnosed cancer may modify quality of diabetes' management, as suggested by current guidelines.
METHODS: Adherence to guideline composite indicator (GCI), a process indicator including one annual assessment of HbA1c and at least two among eye examination, serum lipids measurement and microalbuminuria, was evaluated between years 2011-2012 and 2014-2015 in 158,069 diabetic patients living in Tuscany, Italy, on 1 January 2011 and surviving on 31 December 2015, of whom 661 were hospitalized in index year 2013 for a surgery procedure due to a newly incident cancer. Difference in GCI modification (DELTA_GCI) of these patients was compared with that of diabetic people without cancer, strictly matched for main confounders by means of a propensity score.
RESULTS: In diabetic patients with cancer, GCI adherence increased by about 8 % between years 2011-2012 and 2014-2015. When compared with controls, DELTA_GCI increased by 6 % in cancer group compared with controls (p < 0.05), but any significance was lost after matching the groups by propensity score (3 %; p = NS).
CONCLUSIONS: Our study suggests that a hospitalization for a surgical procedure due to a newly diagnosed cancer does not influence the compliance to a quality process indicator of diabetes care such as GCI.

AIM: A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC.
MATERIALS AND METHODS: Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables.
RESULTS: PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for SUVmax < 6 vs. 15 % for SUVmax > 6, p = 0.018; 2-year PFS 66 % for TLG < 8.5 vs. 18 % for TLG > 8.5, p = 0.09).
CONCLUSION: A very good diagnostic performance for FDG PET/CT was confirmed in patients with suspected recurrent BC. FDG PET/CT allowed for a change in treatment decision in about 40 % of cases and showed an important prognostic value in assessing PFS and OS.

AIMS: To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis.
METHODS: Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression.
RESULTS: Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival.
CONCLUSIONS: Insulin resistance is associated with the aggressiveness of PDAC.

To gain consensus on the role of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer, a panel of expert oncologists experienced in treating patients with metastatic breast cancer in Italy participated in a Delphi consensus study. The panel reached a full consensus on the efficacy of bevacizumab plus paclitaxel and the clinical meaningfulness of the progression-free survival benefit compared with paclitaxel alone, despite the lack of an overall survival effect in clinical trials. The participants agreed that real-world data support the effectiveness and well-defined safety profile of the regimen. Views on the use of bevacizumab plus paclitaxel in specific patient populations were not unanimous and clinical judgment remains important. Nevertheless, a high level of agreement was reached.

The region of Campania (particularly Naples and Caserta) were subjected to extensive illegal dumping operations of toxic and radioactive wastes since the 1980s. The highly toxic wastes (HTW) dumping operations that have taken place both along the coast and the hinterland, have extremely adverse effects on health, livelihoods and the future prospect of sustainable development of the local population. The toxic wastes dumping in Campania is real and it has compromised (irreversibly) the human health, natural environment, food security and the long-term development prospects of the affected population. To reverse this tragic trend, it is necessery the identification, isolation and reclamation of the polluted sites and full assessment of the nature and the scale of the polluting chemicals and other hazardous wastes. The purpose of this review is to contribute significantly to the available evidence of the long-running toxic waste dumping in Campania and its negative impact on the health of population.

Women who underwent chest radiation therapy (CRT) during pediatric/young-adult age (typically, lymphoma survivors) have an increased breast cancer risk, in particular for high doses. The cumulative incidence from 40 to 45 years of age is 13-20 %, similar to that of BRCA mutation carriers for whom contrast-enhanced magnetic resonance imaging (MRI) is recommended. However, in women who underwent CRT, MRI sensitivity is lower (63-80 %) and that of mammography higher (67-70 %) than those observed in women with hereditary predisposition, due to a higher incidence of ductal carcinoma in situ with microcalcifications and low neoangiogenesis. A sensitivity close to 95 % can be obtained only using mammography as an adjunct to MRI. Considering the available evidence, women who underwent CRT before 30 receiving a cumulative dose ≥10 Gy should be invited after 25 (or, at least, 8 years after CRT) to attend the following program: 1. interview about individual risk profile and potential of breast imaging; 2. annual MRI using the same protocol recommended for women with hereditary predisposition; 3. annual bilateral two-view full-field digital mammography or digital breast tomosynthesis (DBT) with synthetic 2D reconstructions. Mammography and MRI can be performed at once or alternately every 6 months. In the case of MRI or contrast material contraindications, ultrasound will be performed instead of MRI. Reporting using BI-RADS is recommended. At the age for entering population screening, the individual risk profile will be discussed with the woman about opting for only mammography/DBT screening or for continuing the intensive protocol.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure.
METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes.
RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT.
CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer.
ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.