Adaptation and validation of an Italian version of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI).

OBJECTIVE: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) is a measure of health-related quality of life (HRQoL) in advanced hormone-resistant prostate cancer. In this study, we aimed at performing a cross-cultural adaptation and validation of the Italian version of the PROSQOLI. PATIENTS AND METHODS: The original version of the PROSQOLI underwent several turnarounds of translations. A total of 472 patients treated with radical prostatectomy, radiotherapy or medical therapy were enrolled for the validation of the questionnaire. The PROSQOLI was administered together with the SF-12. Reliability indexes were calculated by using Cronbach alpha. To evaluate the validity of the construct, relationships between PROSQOLI and SF12 were assessed. The ANOVA test was used to evaluate the differences between groups of patients who had received different treatments. RESULTS: The reliability coefficient was 0.91. Item-to-total correlation indices were in most cases >0.70. The correlation between the scores of the PROSQOLI and those of the SF-12 questionnaire was high (r=0.8139, p<0.0001). The ANOVA test showed significant differences between groups (p<0.01) based on age, recurrence risk and treatment. CONCLUSIONS: The adaptation process showed that the PROSQOLI Italian version has high reliability and presents both convergent and discriminant validity. This version of the tool can be used to assess HRQoL in Italian men who underwent radical treatment for advanced prostate cancer.

PD-L1 marks a subset of melanomas with a shorter overall survival and distinct genetic and morphological characteristics.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is a cell surface molecule that plays a critical role in suppressing immune responses, mainly through binding of the PD-1 receptor on T lymphocytes. PD-L1 may be expressed by metastatic melanoma (MM). However, its clinical and biological significance remains unclear. Here, we investigated whether expression of PD-L1 in MM identifies a biologically more aggressive form of the disease, carrying prognostic relevance. PATIENTS AND METHODS: PD-L1 expression was analyzed by immunohistochemistry using two different antibodies in primary tumors and paired metastases from 81 melanoma patients treated at a single institution. Protein expression levels were correlated with PD-L1 mRNA, BRAF mutational status and clinical outcome. PD-L1(+) and PD-L1(-) subsets of the A375 cell line were stabilized in vitro and compared using gene expression profiling and functional assays. Results were confirmed using xenograft models. RESULTS: PD-L1 membrane positivity was detected in 30/81 (37%) of patients. By multivariate analysis, Breslow thickness and PD-L1 membrane positivity were independent risk factors for melanoma-specific death {PD-L1 5% cutoff [hazard ratio (HR) 3.92, confidence interval (CI) 95% 1.61-9.55 P < 0.003], PD-L1 as continuous variable (HR 1.03, 95% CI 1.02-1.04 P < 0.002)}. PD-L1 expression defined a subset of the BRAF-mutated A375 cell line characterized by a highly invasive phenotype and by enhanced ability to grow in xenograft models. CONCLUSIONS: PD-L1 is an independent prognostic marker in melanoma. If confirmed, our clinical and experimental data suggest that PD-L1(+) melanomas should be considered a disease subset with distinct genetic and morpho-phenotypic features, leading to enhanced aggressiveness and invasiveness.

Genetic association between bipolar disorder and 524A>C (Leu133Ile) polymorphism of CNR2 gene, encoding for CB2 cannabinoid receptor.

INTRODUCTION: Several studies provided evidence that the endocannabinoid system (ECS) is involved in psychiatric diseases, like major depression, schizophrenia and bipolar disorder (BD), mainly focusing on CB1 cannabinoid receptor, and FAAH, the fatty acid amide hydrolase involved in endocannabinoid metabolism. In this study we investigated the possible association of BD with three missense SNPs, of the gene CNR2, encoding for CB2 cannabinoid receptor. METHODS: The possible association between BD and three CNR2 missense SNPs, namely rs2501432 (315A>G; Arg63Gln), rs41311993 (524C>A; Leu133Ile) and rs2229579 (1073C>T; Tyr316His), was investigated through a case-control study. Eighty patients and one hundred and sixty healthy subjects were recruited. Allele Specific Oligonucleotide (ASO)-PCR and restriction fragment length polymorphism (RFLP) methods were used for genotyping. RESULTS: A statistically significant association was found between BD and the CNR2 524C>A; Leu133Ile (P(χ(2)) = 0.001; OR = 4.74; 95% C.I. = 2.52-10.50) while no statistically significant difference between BD and control group was observed for the other two SNPs. CONCLUSION: Though further investigations are necessary to confirm this data, our results suggest that CB2 cannabinoid receptor may play a role in BD.

Expression of gemcitabine- and cisplatin-related genes in non-small-cell lung cancer.

The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA) and ribonucleotide-reductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine-cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.

Recent applications of the sentinel lymph node concept: preliminary experience in prostate cancer.

AIMS AND BACKGROUND: Following the widespread use of radioguided surgery (RGS) in melanoma and breast cancer, we applied this new surgical strategy to prostate cancer (PC). The aims of this study were 1) to evaluate the accuracy of RGS in the detection of prostatic sentinel lymph nodes (SLN), and 2) to verify if pelvic lymphadenectomy (LAD) is an accurate means to detect solitary micrometastases. STUDY DESIGN: We investigated 48 patients with PC confirmed by transrectal biopsy who underwent radical prostatectomy and bilateral LAD. A dose of 99mTc-labeled nanocolloid particles was injected into the prostate after needle positioning by ultrasonography. Serial imaging was obtained with a gamma camera, identifying 1) the first radioactive lymph node (sentinel lymph node, SLN); 2) other radioactive lymph nodes, and 3) non-active lymph nodes. RESULTS: Forty-three SLNs were identified in 48 patients. Twenty SLNs were located at unusual sites with respect to the extent of conventional LAD. Five SLNs were positive for micrometastases and two of these were located outside the usual LAD area. No micrometastases were found in any of the remaining lymph nodes (active and non-active). CONCLUSIONS: These preliminary results are in agreement with the few previous scientific contributions available on this topic and indicate that it is possible to reduce the extent and duration of surgery and necessary to reevaluate the conventional sites of lymphatic drainage.

High-dose epirubicin in the prophylactic treatment of T1G2 superficial bladder tumors.

OBJECTIVES: To evaluate the activity and safety of intravesical instillations of 80 mg epirubicin in a selected patient population with T1G2 primary and multiple superficial bladder tumors. To assess the completeness of the transurethral resection (TUR) at 4 weeks (second look) and to compare the histology of local and review pathology. METHODS: One hundred and sixty-nine patients have been histologically assessed both locally and extramurally for T1G2 superficial bladder tumors. Epirubicin (80 mg/instillation) started within 20 days after TUR was administered weekly during the first month and then monthly for another 11 months. Assessments for relapse were carried out according to the standard methods. RESULTS: Histological consistency for T1G2 between local and extramural assessments was found in 85.2% of cases. At the median follow-up time of 38 months, the overall relapse rate was 43.3%. Treatment was very well tolerated: no systemic adverse events were reported and local adverse events were confined to chemical cystitis which in 3% required treatment discontinuation. CONCLUSIONS: Epirubicin (80 mg/instillation) appeared effective in the prophylaxis of relapse in primary and multiple T1G2 superficial bladder tumors. A second TUR at 3-4 weeks is necessary in T1 tumors. Excellent concordance between local and review pathology was found.

[Does PSA density of the transition zone represent a useful parameter in the diagnosis of prostate carcinoma?]. / PSA density della zona di transizione rappresenta un parametro utile nella diagnostica del carcinoma prostatico?

Prostate specific antigen (PSA) has unequivocally proved its clinical usefulness ad a serum marker for prostate cancer. In order to enhance the specificity of serum PSA, several diagnostic parameters have been employed including PSA density of transition zone (TZ). The authors report their experience on the efficacy of PSA density TZ with level of PSA < 4 ng/ml, between 4-10 ng/ml, > 10 ng/ml, in the diagnostic of prostate cancer. The PSA density of TZ resulted uscless for PSA levels < 4 ng/ml, but improved the diagnostic specificity associated to PSA serum in the PSA levels ranging between 4-10 ng/ml and > 10 ng/ml.