G. La Torre

Fatty acid synthase expression in melanoma.

Background: Fatty acid synthase (FAS), the key enzyme responsible for the synthesis of fatty acids, is weakly expressed in some normal human tissues. Recently, FAS has been demonstrated to be overexpressed in many non‐neoplastic highly proliferative lesions and in aggressive carcinomas with poor outcome, including colon, breast and ovary carcinomas.

Predictive Role of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase and Thymidine Phosphorylase Expression in Colorectal Cancer Patients Receiving Adjuvant 5-Fluorouracil

Objective: The combined assessment of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) gene expressions in metastatic colorectal cancer has been reported to be able to predict the efficacy of fluoropyrimidine-based chemotherapy. In order to evaluate the prognostic role in the adjuvant setting, we investigated the TS, DPD and TP expression in primary tumors of colorectal cancer patients treated with 5-fluorouracil (5-FU). Methods: TS, DPD and TP expression levels were determined by immunohistochemistry in paraffin-embedded primary tumor tissues from 62 patients with Dukes’ stage B and C colorectal cancers who underwent surgery and received adjuvant systemic chemotherapy with 5-FU. The median follow-up was 90 months (range 17–127). Results: Dukes’ stage C cancer and high TS expression were independent markers of poor prognosis for disease-free survival (DFS; p = 0.0009 and p = 0.007, respectively) and overall survival (OS; p = 0.0005 and p = 0.011, respectively). By multivariate analysis, patients with high DPD expression had significantly shorter DFS (p = 0.007) and OS (p = 0.005) compared to patients with low DPD expression. In the combined analysis of 2 markers, patients with low TS and low DPD had the best outcome in terms of DFS (p = 0.007) and OS (p = 0.03). The analysis of all 3 proteins showed that the patients with low expression of all 3 markers had significantly longer DFS (p = 0.04) and OS (p = 0.01) than patients with a high value of any one of the protein expressions. However, the joint analysis of 3 markers (group with TS–/DPD–/TP–) could not identify a subgroup of patients with a better prognosis compared to the analysis of 2 markers (group with TS–/DPD–). The analysis of Dukes’ stage C cancer patients confirmed a significant benefit in terms of DFS and OS (p = 0.001 and p = 0.006, respectively) when all 3 markers had low expression. We also found a positive significant correlation between TS and TP protein expression (p = 0.033). Conclusions: This retrospective investigation suggests that the combined assessment of TS and DPD may be useful to evaluate the prognosis of patients with Dukes’ B and C colon carcinoma receiving 5-FU adjuvant chemotherapy. The role of TP as a predictor for 5-FU-based therapy needs further investigations.

DIFFUSION-WEIGHTED IMAGING IN BREAST LESION EVALUATION

PurposeThe purpose of this study was to investigate the ability of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in the detection and characterisation of breast lesions.Materials and methodsFrom September 2005 to September 2007, 86 patients with breast lesions who underwent magnetic resonance imaging (MRI) in our department were included in our study. MRI was performed with a 1.5-T unit using a standard protocol including DWI sequence. For each breast lesion, the ADC value was calculated and compared with that of normal breast tissue and to the definitive pathological diagnosis. Mann-Whitney U and Kruskal-Wallis tests were used for statistical analysis.ResultsA total of 126 breast lesions were detected. Pathology results revealed 100 malignant and 26 benign lesions. Mean diameter of lesions was 26.02 mm (range 4–90 mm), including 52 lesions ≤15 mm in size. Mean ADC value of normal glandular tissue was 1.55×10−3 mm2/s. Mean ADC value of malignant lesions was 0.97×10−3 mm2/s. Mean ADC value for benign lesions was 1.66×10−3 mm2/s. Benign lesions showed ADC values significantly higher than malignant lesions (p<0.0001).ConclusionsDWI provides reliable information to support MRI diagnosis of breast masses. ADC value appears a promising adjunctive parameter in distinguishing malignant from benign breast lesions.RiassuntoObiettivoLo scopo di questo lavoro è stato quello di valutare l’utilità dell’imaging di diffusione nella caratterizzazione delle lesioni mammarie.Materiali e metodiSono stati inclusi nel nostro studio 86 pazienti con lesione sospetta della mammella inviate all’esecuzione di risonanza magnetica (RM) mammaria presso il nostro Dipartimento da settembre 2005 a settembre 2007. La RM è stata eseguita con apparecchio da 1,5 T; il protocollo di studio includeva una sequenza di diffusione (DWI). Per ogni paziente è stato calcolato il valore del coefficiente di diffusione apparente (ADC) delle lesioni individuate e del parenchima ghiandolare controlaterale. Il valore ADC relativo alle lesioni è stato poi confrontato con la diagnosi patologica definitiva. I test di Mann-Whitney U e Kruskal-Wallis sono stati utilizzati per l’analisi statistica.RisultatiSono state identificate 126 lesioni. L’esame istopatologico ha rivelato la presenza di 100 lesioni maligne e 26 lesioni benigne. Il diametro medio delle lesioni è stato di 26,02 mm (range: 4–90 mm), di cui 52 con diametro ≤15 mm. L’ADC medio del tessuto ghiandolare normale è stato di 1,55×10−3 mm2/s. L’ADC medio delle lesioni maligne è stato di 0,97×10−3 mm2/s. L’ADC medio delle lesioni benigne è stato di 1,66×10−3 mm2/s. Le lesioni benigne hanno mostrato valori di ADC significativamente più alti rispetto alle lesioni maligne (p<0,0001).ConclusioniLa DWI fornisce utili informazioni alla diagnosi di lesioni mammarie in RM. Il valore di ADC sembra un parametro aggiuntivo promettente nella distinzione tra lesioni maligne e benigne della mammella.

Prognostic value of ventricular arrhythmias and heart rate variability in patients with unstable angina

Objectives: To assess the prognostic value of ventricular arrhythmias (VA) and heart rate variability (HRV) in patients with unstable angina. Design: Multicentre prospective study. Setting: 17 cardiological centres in Italy. Patients: 543 consecutive patients with unstable angina and preserved left ventricular function (ejection fraction ⩾40%) enrolled in the SPAI (Stratificazione Prognostica dell’Angina Instabile) study. Methods: Patients underwent 24 h ECG Holter monitoring within 24 h of hospital admission. Tested variables were frequent ventricular extrasystoles (⩾10/h), complex (that is, frequent or repetitive) VA, and bottom quartile values of time-domain and frequency-domain HRV variables. Primary end points were in-hospital and six-month total and cardiac deaths. Results: Eight patients died in hospital (1.5%) and 32 (5.9%, 29 cardiac) during follow up. Both complex VA and frequent extrasystoles were strongly predictive of death in hospital and at follow up, even after adjustment for clinical (age, sex, cardiac risk factors and history of myocardial infarction) and laboratory (troponin I, C reactive protein and transient myocardial ischaemia on Holter monitoring) variables. At univariate analysis bottom quartile values of three HRV variables (standard deviation of RR intervals index, low-frequency amplitude and low to high frequency ratio) were associated with in-hospital death, and bottom quartile values of most HRV variables predicted six-month fatal events. At multivariate Cox survival analysis reduced low-frequency amplitude was consistently found to be independently associated with fatal end points. Conclusion: In patients with unstable angina with preserved myocardial function, both VA and HRV are independent predictors of in-hospital and medium-term mortality, suggesting that these factors should be taken into account in the risk stratification of these patients.

Variables influencing quality of life and disability in Charcot Marie Tooth (CMT) patients: Italian multicentre study.

The purpose of this study was to assess the variables that influence quality of life (QoL) and disability in patients with Charcot-Marie-Tooth disease (CMT). We performed a prospective multicentre study using validated clinical disability and QoL measurements. Multivariate analysis was performed using QoL as a dependent variable and duration of symptoms, age, gender and CMT type, depression and disability measurements as independent variables. We enrolled 211 patients. QoL was highly significantly deteriorated with respect to the Italian normative sample. The physical aspect of QoL was mainly related to disability but it does not increase with the age, probably because of an adaptation between expectation and reality. The mental QoL is influenced by depression (hence we have to consider this aspect approaching CMT patients). Moreover, we observed that women complained of more severe symptoms than men. Finally, some CMT subtypes are related to more severe bodily pain symptoms than others. Multiperspective assessment of CMT showed new aspects of this disease, mainly regarding (1) differences between men and women and (2) the crucial role of pain and depression.

Solid breast mass characterisation: use of the sonographic BI-RADS classification

PurposeThe aim of this study was to assess the reliability of the sonographic Breast Imaging Reporting and Data System (BI-RADS) classification in differentiating benign from malignant breast masses.Materials and methodsA total of 292 female patients with breast masses undergoing biopsy between November 2004 and March 2006 in our department were included in this study. All lesions were classified according to the sonographic BI-RADS lexicon. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for the sonographic BI-RADS lexicon and PPV and NPV for each lesion category and each sonographic descriptor were calculated. The χ2 test and the Fischer exact test were used to evaluate our results.ResultsUnivariate analysis showed a significant difference between malignant and benign groups with regard to morphology (p<0.001), horizontal-vertical diameter ratio<1 (p<0.002), orientation (p<0.001), noncircumscribed margins (p<0.001), echogenic halo (p<0.001), hypoechoic pattern (p=0.035), shadowing (p<0.001) and surrounding tissue alterations (p=0.001). The cumulative risk for malignancy was 64 and 10 times higher, respectively, in categories 5 and 4 than in category 3.ConclusionsThe sonographic BI-RADS lexicon is an important system for describing and classifying breast lesions.RiassuntoObiettivoValutare l’attendibilità della classificazione BI-RADS nella caratterizzazione ecografica delle lesioni solide della mammella.Materiali e metodiSono state studiate 292 pazienti con nodulo mammario sottoposto a biopsia nel nostro Dipartimento dal novembre 2004 al marzo 2006. Ogni lesione è stata studiata ecograficamente e classificata secondo i criteri BI-RADS. Sono stati calcolati specificità, sensibilità, accuratezza, valore predittivo positivo e negativo (VPP e VPN) del sistema BI-RADS, VPP e VPN per ogni classe e per ogni descrittore ecografico. Sono stati adottati il test del χ2 e il test esatto di Fischer per valutare la significatività dei nostri risultati.RisultatiDall’analisi univariata sono emerse differenze statisticamente significative tra il gruppo lesioni maligne e quello lesioni benigne rispetto alle seguenti variabili: forma (p<0,001), rapporto dei diametri inferiori a 1 (p<0,002), orientamento (p<0,001), margini non circoscritti (p<0,001), alone iperecogeno (p<0,001), ipoecogenecità (p=0,035), sbarramento (p<0,001), presenza di alterazioni del parenchima circostante (p=0,001). Dall’analisi multivariata è risultato che il rischio di avere una lesione maligna è in classe V e IV, rispettivamente 64 e 10 volte maggiore rispetto alla classe III.ConclusioniIl nostro studio conferma che la classificazione ecografica BI-RADS costituisce un accurato sistema per la descrizione e il management delle lesioni mammarie.

A Clinical Trial of Oral Hyposensitization in Systemic Allergy to Nickel

Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema).

Suicide among first-generation and second-generation immigrants in Sweden: association with labour market marginalisation and morbidity

Background Previous research suggests that first-generation immigrants have a lower suicide risk than those both born in Sweden and with both parents born in Sweden (natives), while the suicide risk in the second generation seems higher. The aim of this study was to investigate to what extent suicide risk in first-generation and second-generation (both parents born abroad) and intermediate-generation (only one parent born abroad) immigrants compared with natives is associated with sociodemographic factors, labour market marginalisation and morbidity. Methods A prospective population-based cohort study of 4 034 728 individuals aged 16–50 years was followed from 2005 to 2010. HRs for suicide were calculated for first-generation, intermediate-generation and second-generation immigrants compared with natives. Analyses were controlled for sociodemographic factors, morbidity and labour market marginalisation. Results The HR of suicide was significantly lower in first-generation immigrants (HR 0.83 CI 0.76 to 0.91), and higher in second-generation (HR 1.32, CI 1.15 to 1.52) and intermediate-generation immigrants (HR 1.20, CI 1.08 to 1.33) in comparison to natives. The excess risk was explained by differences in sociodemographics, morbidity and labour market marginalisation. In the fully adjusted models, a higher HR remained only for the Nordic second generation (HR 1.29, CI 1.09 to 1.52). There were no sex differences in HRs. Conclusions The risk of suicide was shown to be lower in the first generation and higher in the second generation compared with natives. The higher HR in the Nordic second generation was not explained by differences in sociodemographics, labour market marginalisation and morbidity. Further research is warranted to investigate factors underlying this excess risk.

Human papillomavirus and cancerous diseases of the head and neck: a systematic review and meta-analysis.

The increasing incidence of head and neck cancer (HNSCC) highlights the need to better understand the role of human papillomavirus (HPV) in the development of these cancers. The aims of this study were to conduct a systematic review and a meta-analysis concerning observational studies on the association between HPV infection and HNSCC and to quantify this association, thereby obtaining a reliable estimation of the risk of HPV infection in the development of head and neck cancer. Literature searches were performed using PubMed and Scopus databases. StatsDirect 2.7.8 program was used for the analysis. We found 15 case-control studies, 63 prevalence studies, and no cohort studies. The pooled odds ratio (OR) for all the included case-control studies resulted in a value of 1.63 (95% CI 1.27-2.09; P < 0.0001). The highest pooled OR resulted from the analysis of all the studies that examined HPV 16 genotype in association oral cavity (OR 5.36; 95% CI 1.4-20). The strong evidence of association between HPV infection and HNSCC highlights the importance of the introduction of specific tests in the cancer prevention practices to evaluate the presence of the virus, especially in the oral cavity, and the possibility of an extension of the vaccine anti-HPV in the male population too.

IN-RATIO: a new test to increase diagnostic sensitivity in ulnar nerve entrapment at elbow.

OBJECTIVE Motor conduction velocity may yield false-negative results in mild ulnar nerve entrapment at elbow (UNE). There is evidence that the clinical heterogeneity of UNE may be due to the different involvement of fascicles. We hypothesized that, if fibres to FDI are more damaged than fibres to ADM, a relative slowing of motor conduction velocity (CV) at the segment across the elbow recording from FDI (FDI-CV) versus CV at the same segment recording from ADM (ADM-CV) would occur. METHODS We calculated the ratio between FDI-CV and ADM-CV (IN-RATIO) in 60 consecutive UNE patients, 40 norms, and 16 patients with lower cervical radiculopathy. The UNE sample consisted of (1) patients with neurophysiological evidence (UNE NF+), (2) patients without neurophysiological evidence (UNE NF-). We evaluated the possible usefulness of the IN-RATIO to increase sensitivity in diagnosing UNE. RESULTS The IN-RATIO was lower in the UNE NF- than in norms (p<0.001) and cervicobrachialgia sample (p=0.02). We found that if the IN-RATIO is <or=0.97, its sensitivity in diagnosing UNE NF- is 68%, specificity 91%. CONCLUSIONS Fibres to FDI have a higher susceptibility to damage than fibres to ADM, and the IN-RATIO is a useful neurophysiological parameter to increase diagnostic sensitivity. SIGNIFICANCE Our results demonstrate the usefulness of a new neurophysiological parameter in improving diagnosis of UNE.