Sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents ejection fraction reduction, reduces myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity.

Background: Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models. Methods: Cardiomyocytes were exposed to DOXO alone or combined with dapagliflozin (DAPA) at 10 and 100 nM for 24 h; cell viability, iATP, and Ca++ were quantified; lipid peroxidation products (malondialdehyde and 4-hydroxy 2-hexenal), NLRP3, MyD88, and cytokines were also analyzed through selective colorimetric and enzyme-linked immunosorbent assay (ELISA) methods. Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg), or DOXO combined with DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory chemokines (IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed. Results: DAPA exerts cytoprotective, antioxidant, and anti-inflammatory properties in human cardiomyocytes exposed to DOXO by reducing iATP and iCa++ levels, lipid peroxidation, NLRP-3, and MyD88 expression. Pro-inflammatory intracellular cytokines were also reduced. In preclinical models, DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in the DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1ß, IL-6, TNF-α, G-CSF, and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in the DOXO group; on the other hand, their expression was reduced in the DAPA-DOXO group. Troponin-T, B-type natriuretic peptide (BNP), and N-Terminal Pro-BNP (NT-pro-BNP) were strongly reduced in the DOXO-DAPA group, revealing cardioprotective properties of SGLT2i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression. Conclusion: The overall picture of the study encourages the use of DAPA in the primary prevention of cardiomyopathies induced by anthracyclines in patients with cancer.

Intestinal, intestinal-type and intestine-localized metastatic adenocarcinoma. Immunohistochemical approach to the differential diagnosis.

The pathologist is often called to define the origin of tumors through the help of ancillary studies, mainly immunohistochemical stainings. In this setting, the differential diagnosis between intestinal adenocarcinomas, other tumors with intestinal-type morphology, and adenocarcinomas metastatic to the bowel can be particularly difficult. In such cases, an accurate assessment of the disease is required to address the patients to the optimal treatment. Immunohistochemistry offers the use of multiple antibodies: the integrated evaluation of specific stainings can lead to a correct diagnosis. Particularly, the use of cytokeratins, mucins, and ß-catenin could be of great help in most cases. In addition, recently, novel specific markers such as SATB2 and AMACR have been introduced, improving the utility of immunohistochemistry in the differential diagnosis of intestinal-type and intestinal adenocarcinomas.

The potential diagnostic and predictive role of anaplastic lymphoma kinase (ALK) gene alterations in melanocytic tumors.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

Diagnosis of anaplastic large cell lymphoma on late peri-implant breast seroma: Management of cytological sample by an integrated approach.

INTRODUCTION: Peri-implant breast seroma is a late clinical presentation of reconstructive surgery or augmentation mammoplasty with breast implants. Pre-operative cytological evaluation of the peri-implant breast seroma is a common clinical approach, showing mainly an inflammatory reaction or more rarely a breast implant-associated anaplastic large cell lymphoma. Herein, we reported the role of cytology in the evaluation of peri-implant breast seroma and its critical pre-operative implications. METHODS: Eight cases of peri-implant breast seroma from files at Luigi Vanvitelli University were identified between January and December 2017. In all cases, seroma was aspirated; cytospins were performed and stained by Papanicolaou stain; finally, in all cases, a cell block was obtained for immunocytochemical evaluation and, in one case, for FISH to detect ALK1-gene translocation. RESULTS: The median age of patients was 48 years and the mean time between the implant placement and the occurrence of peri-implant breast seroma was 18 months. Microscopic examination showed breast implant-associated anaplastic large cell lymphoma in one case, aspecific inflammatory reaction in six cases and silicon-associated reaction in one case. CONCLUSIONS: Peri-implant breast seroma may be caused by several pathological conditions with different clinical behaviour. A proper cytological approach to peri-implant breast seroma allows a correct differential diagnosis between inflammatory conditions and breast implant-associated anaplastic large cell lymphoma and an appropriate management of the patient.

Epigenetic Changes Induced by Green Tea Catechins a re Associated with Prostate Cancer.

Prostate cancer is one of the most difficult cancers to treat especially when it becomes hormone resistant such as castrate resistant prostate cancer (CRPC) and subsequent metastatic CRPC. Apart from the genetic alterations in prostate cancer, epigenetic modifications also play an important role in the development and neoplastic progression of this disease. These include DNA methylation, histone modifications, and non-coding microRNAs. miRNAs are a novel class of small endogenous single-stranded non-coding RNAs of 19-25 nucleotides in length that typically silence gene expression. Considering the reversibility of epigenetic alterations in early carcinogenesis process, reversion (correction) of these modifications by green tea catechins could be a promising strategy for cancer chemoprevention and therapy. Recent evidence suggests that green tea catechins such as epigallocatechin gallate (EGCG) not only act as epigenetic modulators but can also modify miRNA expression and their target mRNAs, consistently contributing to the inhibition of prostate carcinogenesis. Various studies also indicate that several green tea polyphenols (GTPs) exert synergistic effects with other cancer chemotherapeutic agents. Therefore, the use of appropriate combinations of green tea catechins with the existing chemotherapeutics will lead to a reduction in side effects without decreasing the chemotherapeutic effects. This review will summarize the key results from recent studies detailing the effects of green tea catechins such as EGCG on epigenetic alterations and miRNA expression in prostate cancer.

Ultrasound imaging of oral fibroma: a case report.

Oral mucosa is constantly under the influence of various internal and external stimuli, therefore it is interested by a range of developmental disorders, irritation, inflammation, and neoplastic conditions. Traumatic fibroma is one of these lesions. The aim of this work is to obtain an ultrasound characterization of a lip fibroma with a high frequency probe (8-18 MHz) as feasibility and experimental model of this non-invasive technique in the oral mucosa compared with its histo-pathological section. Ultrasound characterization of a fibroma in a 50-year-old patient in the right retro commissural area of mucosa was performed. The ultrasound images were compared with its histological image. Fibroma is a traumatic lesion clinically recognizable and with a complex and well-defined histopathology structure. Although further investigations are necessary to determine the potential of ultrasonographic images as an aid in the diagnosis of oral lesions, this case report might be a model for ultrasound imaging compared with its histological section.

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc.

Tumor characteristics and prognosis in familial breast cancer.

BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome. METHODS: We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months. RESULTS: BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28-0,93) p = 0.028). CONCLUSIONS: The biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

Body weight and risk of molecular breast cancer subtypes among postmenopausal Mediterranean women.

Breast cancer (BC) is the most common malignant tumor in women, obesity is associated with increased BC incidence and mortality and high levels of circulating insulin may negatively impact on cancer incidence. In the present study, we investigated whether the strength of several anthropometric and metabolic parameters varies between BC molecular subtypes. Eligible cases were 991 non-metastatic BC patients recruited between January 2009 and December 2013. Anthropometric, clinical and immunohistochemical features were measured. Multivariate logistic regression models were built to assess HER2 positive BC risk, comparing (a) triple positive (TP) with luminal A, luminal B and triple negative (TN) and (b) HER2-enriched group with luminal A, luminal B and TN. We stratified patients in pre- and post-menopause: significant differences emerged for luminal A in relation to age: they were more likely to be older compared to other groups. Among postmenopausal patients, the adjusted multivariate analysis showed that high BMI and high waist circumference were inversely correlated to TP subtype when compared to luminal B (OR=0.48 and OR=0.49, respectively). Conversely, HOMA-IR was a risk factor for TP when compared to luminal A and TN (OR=2.47 and OR=3.15, respectively). Our findings suggest a potential role of higher abdominal fat in the development of specific BC molecular subtypes in postmenopausal women. Moreover, they support a potential role of insulin resistance in the development of HER2 positive BC, although this role appears to be stronger when hormone receptors are co-expressed, suggesting a difference in the etiology of these two BC subtypes.

Epithelioid angiosarcoma arising in schwannoma of the kidney: report of the first case and review of the literature.

BACKGROUND: Schwannoma and angiosarcoma are infrequent pathologies that have been rarely reported in the kidney. Angiosarcoma is an uncommon malignant tumor presenting a recognizable vascular differentiation. It can develop in any site but the most common locations include the skin, soft tissues, breast, bone, liver, and spleen while renal localization has been very rarely reported in the literature. Schwannoma is a benign peripheral nerve sheath tumor composed of cells with the immunophenotype and ultrastructural features of differentiated Schwann cells. It has a wide anatomical distribution but the most frequent locations include subcutaneous tissues of the extremities and the head and neck region and the retroperitoneal and mediastinal soft tissues. The occurrence of an angiosarcoma in a pre-existing schwannoma is an extremely rare event with <20 cases reported in worldwide literature. In the present study, a renal case of angiosarcoma arising in schwannoma is presented with a detailed review of the pertinent literature. CASE PRESENTATION: A 56-year-old man was admitted with a few days history of lower back pain and hematuria. Abdominal ultrasound showed a mass inside the left renal medulla. Subsequent imaging investigations with computed tomography and magnetic resonance confirmed the presence of the lesion and showed a pulmonary metastasis. CONCLUSIONS: The final histopathological examination led to the diagnosis of epithelioid angiosarcoma arising in a schwannoma. The patient came to death a few months later due to a massive hemothorax. To the best of our knowledge, the present is the first case of an angiosarcoma arising in a schwannoma of the kidney.

Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies.

BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms. METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors. RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users. CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Diabetes mellitus and the risk of bladder cancer: an Italian case­control study.

BACKGROUND: Diabetes mellitus has been associated with an increased risk of bladder cancer, although the evidence is still open to discussion. METHODS: We examined this association using data from a multicentre Italian case­control study, conducted between 2003 and 2014 on 690 bladder cancer cases and 665 frequency-matched hospital controls. Odds ratios (ORs) for diabetes were estimated by unconditional multiple logistic regression models, after allowance for major known risk factors for bladder cancer. RESULTS: One hundred and twelve (16.2%) cases and 57 (8.6%) controls reported a diagnosis of diabetes mellitus, corresponding to a multivariate OR of 2.09 (95% confidence interval (CI): 1.46­3.01). Bladder cancer risk increased with duration of diabetes (OR 1.92 for 1­ <5 years, 1.63 for 5­ <10 years, 2.39 for 10­ <15 years, and 2.58 for ≥15 years). The increased risk of bladder cancer was consistent in strata of age and education, whereas it was somewhat lower (although not significantly) in women (OR 1.18), in never (OR 1.31) and current (OR 1.42) smokers, and in subjects with a body mass index <25 kg m(-2) (OR 1.48). CONCLUSION: The present study provides further support of a role of diabetes in bladder cancer aetiology, although some residual confounding by tobacco, body mass index, or other unmeasured covariates may partly explain the association observed.

Factors predictive of pelvic lymph node involvement and outcomes in melanoma patients with metastatic sentinel lymph node of the groin: A multicentre study.

INTRODUCTION: The optimal extent of the groin lymph node (LN) dissection for melanoma patients with positive sentinel LN biopsy is still debated and no agreement exist on dissection of pelvic LN. This study aimed at investigating predictors of pelvic LN metastasis and prognostic significance of having metastasis in the pelvic LNs. METHODS: Clinicopathologic data of 740 patients with positive groin sentinel LN who underwent ilioinguinal completion LN dissection at four Italian centre were analysed. Multivariable logistic and Cox regression analysis was used to identify independent predictors of pelvic LN metastasis and to adjust prognostic significance of pelvic LN metastasis. RESULTS: More than a quarter (26%) of patients had positive non-SLNs after inguinal and pelvic lymphadenectomy, which were located in their pelvis in the 12% of cases. Older patients [(OR) 1.69; 95% confidence interval (CI) 1.02-2.78] having thick primary (OR 1.6; 95% CI, 1.01-2.53) and ≥ 2 positive SLNs (OR 2.5; 95% CI, 1.4-4.47) were more likely to harbour pelvic LN metastasis. Interestingly, 4% of all patients (34% of patients with positive pelvic LNs) had pelvic LN metastasis with negative inguinal LNs. Pelvic LN metastasis was independently associated with higher risk of recurrence and lower survival. 5-year disease free and overall survival was 30% and 50%, respectively, for patients with pelvic LN metastasis. CONCLUSIONS: Pelvic LNs are frequently positive after ilioinguinal lymphadenectomy and it should be considered for all patients, especially those who are older, have thick primary and ≥ 2 positive SLN. Patients with pelvic LN metastasis have worse prognosis.

Red meat and cancer risk in a network of case-control studies focusing on cooking practices.

BACKGROUND: Consumption of red meat has been related to increased risk of several cancers. Cooking methods could modify the magnitude of this association, as production of chemicals depends on the temperature and duration of cooking. METHODS: We analyzed data from a network of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1465 oral and pharyngeal, 198 nasopharyngeal, 851 laryngeal, 505 esophageal, 230 stomach, 1463 colon, 927 rectal, 326 pancreatic, 3034 breast, 454 endometrial, 1031 ovarian, 1294 prostate and 767 renal cancer cases. Controls included 11 656 patients admitted for acute, non-neoplastic conditions. Odds ratios (ORs) and confidence intervals (CIs) were estimated by multiple logistic regression models, adjusted for known confounding factors. RESULTS: Daily intake of red meat was significantly associated with the risk of cancer of the oral cavity and pharynx (OR for increase of 50 g/day = 1.38; 95% CI: 1.26-1.52), nasopharynx (OR = 1.29; 95% CI: 1.04-1.60), larynx (OR = 1.46; 95% CI: 1.30-1.64), esophagus (OR = 1.46; 95% CI: 1.23-1.72), colon (OR = 1.17; 95% CI: 1.08-1.26), rectum (OR = 1.22; 95% CI:1.11-1.33), pancreas (OR = 1.51; 95% CI: 1.25-1.82), breast (OR = 1.12; 95% CI: 1.04-1.19), endometrium (OR = 1.30; 95% CI: 1.10-1.55) and ovary (OR = 1.29; 95% CI: 1.16-1.43). Fried meat was associated with a higher risk of cancer of oral cavity and pharynx (OR = 2.80; 95% CI: 2.02-3.89) and esophagus (OR = 4.52; 95% CI: 2.50-8.18). Risk of prostate cancer increased for meat cooked by roasting/grilling (OR = 1.31; 95% CI: 1.12-1.54). No heterogeneity according to cooking methods emerged for other cancers. Nonetheless, significant associations with boiled/stewed meat also emerged for cancer of the nasopharynx (OR = 1.97; 95% CI: 1.30-3.00) and stomach (OR = 1.86; 95% CI: 1.20-2.87). CONCLUSIONS: Our analysis confirmed red meat consumption as a risk factor for several cancer sites, with a limited impact of cooking methods. These findings, thus, call for a limitation of its consumption in populations of Western countries.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

Metabolic syndrome and hepatocellular carcinoma risk.

BACKGROUND: Hepatocellular carcinoma (HCC) has been associated to diabetes and obesity, but a possible association with the metabolic syndrome (MetS) and its potential interaction with hepatitis is open to discussion. METHODS: We analysed data from an Italian case-control study, including 185 HCC cases and 404 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models. RESULTS: Among the MetS components, diabetes and obesity (i.e, body mass index (BMI)≥30 kg m(-2)) were positively associated to HCC risk, with ORs of 4.33 (95% CI, 1.89-9.86) and 1.97 (95% CI, 1.03-3.79), respectively. The ORs for the MetS were 4.06 (95% CI, 1.33-12.38) defining obesity as BMI≥25, and 1.92 (95% CI, 0.38-9.76) defining it as BMI≥30. The risk increased with the number of MetS components, up to an almost four-fold excess risk among subjects with ≥2 MetS factors. Among subjects without chronic infection with hepatitis B and/or C, the OR for those with ≥2 MetS components was over six-fold elevated. There was no consistent association in subjects with serological evidence of hepatitis B and/or C infection. CONCLUSION: This study found that the risk of HCC increases with the number of MetS components in subjects not chronically infected with hepatitis viruses.

Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case-control study in Italy.

BACKGROUND: Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18-76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression. RESULTS: Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26-0.79), α-carotene (OR=0.57; 95% CI: 0.33-0.97), and ß-carotene (OR=0.42; 95% CI: 0.24-0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12-3.05). CONCLUSION: Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.

Dietary folates and cancer risk in a network of case-control studies.

BACKGROUND: Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. PATIENTS AND METHODS: The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. RESULTS: For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 µg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. CONCLUSIONS: Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

[Implementing clinical pathways: some practical notes]. / L'implementazione dei percorsi: note pratiche.

The traditional biomedical paradigm is no longer a guarantee of quality for health care, facing increasingly difficult challenges caused by chronic diseases and increasingly fragmented resources that current healthcare systems are dealing with. Health care organizations, considered to be the most complex enterprises of the modern era, must be able to focus on the flow of patients, integrating primary and secondary care through tools such as the Integrated Care Pathways (ICP). This brief discussion attempts to define the ICP its purposes, the elements that characterize it, its limitations and the mechanisms to push for a successful implementation. In order to highlight the elements and basic steps for the creation of an ICP, the authors have compared five different clinical pathways, whose implementation they have contributed to. The comparison was made using two grids: the first showing the essential elements for the definition of lCP and the second one with features that can facilitate their effectiveness. The conclusions of the work show what, pursuing the construction of a pathway, we must never forget: to analyze the gap between the clinical-care activities performed and the theoretical framework provided by the evidence; to see the barriers to change that may impede the implementation; to involve all actors in the system, with particular attention to patients and their associations, and finally to provide a plan for information and education, addressed to health professionals and patients as well.