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Cystic masses of the lateral neck are mostly benign. However, the incidence of metastatic squamous cell carcinoma (SCC) in cervical cystic masses initially diagnosed as benign is quite high in patients older than 40 years. The aim of this study was to compare the diagnostic accuracy of preoperative cytology and intraoperative frozen section (FS) in detecting malignancy in cystic masses of the neck. We reviewed 61 patients who underwent preoperative ultrasound-guided fine-needle aspiration cytology (FNAC) and neck biopsy of a cystic neck mass, and analysed the concordance between FNAC and intraoperative FS with respect to definitive histology. HPV status was also tested. Of 49 eligible cases, the accuracy of preoperative FNAC was 70.5% (weighted kappa 0.53), meaning moderate agreement between cytology and final diagnosis. Intraoperative FS consultations detected 16 cases of SCC metastasis while the remaining 33 cases were negative for SCC, showing perfect agreement with histology. Since FS results were useful in evaluating cystic neck masses, despite a moderate accuracy of cytology, we suggest intraoperative FS analysis for all cystic neck masses. This technique can allow us to switch to therapeutic neck dissection, multiple upper aerodigestive tract biopsies, tongue base mucosectomy, and bilateral tonsillectomy in the same surgical setting.

With the regional law n. 26 of December 30, 2020, the Friuli Venezia Giulia Region wanted to promote the establishment of the Regional Register of Sudden Cardiac Death, with the aim of favoring the study of all those deaths that occurred suddenly and unexpectedly under the age of 50 years in which it is not possible to trace the cause of death with certainty. Such dramatic events, difficult to quantify considering the complexity of data collection, are often accepted with resignation without any further investigation of the possible causes. The Regional Register of Sudden Cardiac Deaths of Friuli Venezia Giulia was born from this premise and from the awareness of the importance of going back with a rigorous scientific methodology and through a multidisciplinary approach, to the diagnosis of hereditary heart diseases which, when determined, allow the enrollment of relatives in a cardiological screening process and, therefore, primary prevention of potentially fatal events. The authors describe the operating procedures feeding the Regional Register and present the results of the first year of activity on 26 cases.

Additional file 1: Table S1. Intralaboratory reproducibility of HPV Selfy according to Meijer’s guidelines. HPV Selfy assay was performed twice on a subpopulation of 521 samples of which 157 samples positive to HC2. Overall concordance observed was 94.6% (kappa value of 0.87). Table S2. Interlaboratory reproducibility of HPV Selfy according to Meijer’s guidelines. HPV Selfy assay was performed in another laboratory (MediChrom) on a subpopulation of 500 samples of which 150 samples positive to HC2. Overall concordance observed was 93.6% (kappa value of 0.85). Table S3. Intra-laboratory reproducibility of genotype findings of HPV Selfy. Data are presented as number of each genotype detected in each run (i.e. run1 and/or run 2), and numbers do not count up to the total number of HR-HPV positive samples due to multiple infections.

Additional file 1: Supplementary Table S1. Automatic definition of cell types by NanoString nSolver Software. Supplementary Table S2. Automatic definition of immune pathways by NanoString nSolver Software. Supplementary Fig. S1. Representative images of cell-to-cell distance analyses. (A) For mean distance between different cell subtypes, the nearest neighbors analysis was used. The mean distance between tumor cells (light blue dots) and the nearest CD8+ cells (red dots) is represented in the figure as an example. (B) The count within analysis was employed to calculate the percentage of reference cells, among the total number of reference cells, which are present within a 20 μm radius from at least one cell of a different phenotype. The percentage of tumor cells (light blue dots) within a 20 μm radius from a CD8+ T lymphocyte (red dots) is represented in the figure as an example. Original magnification X20. Supplementary Table S3. Differentially expressed genes (DEGs) between HPV-positive and HPV-negative (used as baseline) OPSCC patients. Supplementary Fig. S2. Differential expression of immune-related pathways and cell type genes in HPV-positive and HPV-negative OPSCC. Trend plots depicting differential expression of predefined (A) pathway genes and (B) gene expression-based cell types in HPV-positive and HPV-negative OPSCC. Supplementary Table S4. Correlation analysis between immune cell populations in HPV-positive and HPV-negative primary tumors and metastases. Supplementary Fig. S3. Immune cells in primary tumors and related metastases. Density (number of cells/mm2) of different immune cell populations in HPV-positive and HPV-negative primary tumors and metastases. Supplementary Fig. S4. The immune cell contexture of metastases correlates with patient outcome. (A-C) Kaplan-Meier survival curves for disease-free survival according to the immune cell composition of (A) the entire cohort (n = 39), (B) HPV-positive (n = 24) and (C) HPV-negative (n = 15) lymph node metastases. The median cut-off of each immune cell subset density was used to separate high and low infiltrated groups. Log-rank p values, hazard ratios (HR) and 95% confidence intervals (CI) are reported in each graph. Supplementary Fig. S5. The density of immune cells differs between females and males with HPV-positive lesions. Density (number of cells/mm2) of different immune cell populations in females and males with HPV-positive (A) primary tumors and (B) metastases.

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

The aim of the study was to assess whether the reliability of Touch Imprinting Cytology (TIC) of Sentinel lymph node biopsy (SLNB) in skin melanoma patients allows intraoperative decisions regarding simultaneous radical lymphadenectomy to be made. Previous experiences have shown that the limit of TIC in extemporaneous diagnosis was represented by the minimal deposits of the tumor. Many current data seem to show that in this situation radical lymphadenectomy is no longer necessary, so we wondered if TIC could regain importance in the intraoperative management of these patients.TIC results of Sentinel Lymph Nodes Biopsy (SLN) were compared with those of standard histopathological and immunohistochemical examinations.A total number of 110 SLN were detected from 50 melanoma patients.TIC revealed the presence of metastases only in 1 out of 13 melanoma-positive SLN (sensitivity 7.6%). There were no false-positive results of TIC (specificity 100%). The negative predictive value was 75.5%, the positive one 100% with a total diagnostic accuracy of 76%.TIC for SLNs is a reliable method, relatively fast and not very expensive. Although with a very high specificity, its sensitivity was very low, and almost exclusively limited to macro-metastases (2mm). Furthermore, it was not possible to identify a subgroup of patients, based on the characteristics of the primary tumor, in which the method could have been more useful. Finally, even in positive cases, the method rarely reduced the need of a tactic in two stages, principally for the management of the operating room.Melanoma, Sentinel lymph node (SLN), Touch Imprinting Cytology (TIC).Lo scopo dello studio era di valutare se l’affidabilità di Touch Imprinting Cytology (TIC) nella biopsia del linfonodo sentinella (SLNB) nei pazienti con melanoma cutaneo consente di prendere decisioni intraoperatorie riguardanti la linfoadenectomia radicale simultanea. Precedenti esperienze hanno mostrato che il limite del TIC nella diagnosi estemporanea era rappresentato dai depositi minimi del tumore. Molti dati attuali sembrano mostrare che in questa situazione non è più necessaria la linfoadenectomia radicale, quindi ci siamo chiesti se il TIC potesse riacquistare importanza nella gestione intraoperatoria di questi pazienti. I risultati TIC della biopsia del linfonodo sentinella (SLN) sono stati confrontati con quelli degli esami istopatologici e immunoistochimici standard: su 50 pazienti con melanoma sono stati prelevati un totale di 110 SLN, e su questi è stato individuata la presenza di metastasi solo in 1 su 13 SLN melanoma-positivi (sensibilità 7,6%), senza falsi positivi di TIC (specificità 100%). Il valore predittivo negativo era del 75,5%, quello positivo del 100% con una precisione diagnostica totale del 76%. In conclusione la TIC per SLN è un metodo affidabile, relativamente veloce e non molto costoso. Sebbene con una specificità molto elevata, la sua sensibilità risulta molto bassa e quasi esclusivamente limitata alle macrometastasi (2mm). Inoltre, non è stato possibile identificare un sottogruppo di pazienti, in base alle caratteristiche del tumore primario, in cui il metodo avrebbe potuto essere più utile. Infine, anche in casi positivi, il metodo raramente ha ridotto la necessità di una tattica in due fasi, principalmente per la gestione della sala operatoria. Queste considerazioni ci hanno spinto a sospendere l’analisi TIC intraoperatoria a favore di una più accurata ecografica dei linfonodi superficiali ad opera di personale dedicato, da eseguirsi prima di ogni ricerca del linfonodo sentinella.

Objectives: to evaluate the incidence of advanced-stage breast cancer (BC) - an early surrogate indicator of effectiveness of mammography screening - among women who attended the Friuli Venezia Giulia (FVG) Region (Northern Italy) screening programme compared to women who did not attend. Design: retrospective cohort study. Women invited to the first screening round (2006-2007) were identified from the database of the programme. The cohort was record-linked to the archive of women invited to the second round (2008-2009). The definition of attendance to screening was based on attendance to at least one of the two rounds. The incidence of BC was assessed through record linkage with the FVG cancer registry using an anonymous univocal identifier (end of follow-up: 31st December 2013). Three distinct definitions of advanced stage were used: pT2 or greater (pT2+), positive lymph nodes (pN+), and TNM stage II or greater (stage II+). Setting and participants: organized mammography screening programme for women aged 50-69 years in the five regional healthcare districts. Main outcome measures: incidence rate ratio (IRR) between attenders and non-attenders, adjusted for age and deprivation index, with 95% confidence interval (95%CI). Results: the cohort included 104,488 attenders and 49,839 non-attenders. During follow-up (median duration 84 months), 2,717 invasive BCs were diagnosed among attenders and 1,149 among non-attenders. Total incidence rate was 13% higher among attenders (IRR 1.13; 95%CI 1.05-1.21). These, conversely, had a 36% lower rate of pT2+ BC (IRR 0.64; 95%CI 0.56-0.72), a 13% lower rate of pN+ BC (IRR 0.87; 95%CI 0.78-0.98), a 22% lower rate of stage II+ BC (IRR 0.78; 95%CI 0.70-0.87), and a 32% lower rate of mastectomy (IRR 0.68; 95%CI 0.60-0.78). Conclusions: attenders had lower incidence rates of advanced-stage BC. This early effect is suggestive of a future impact of the screening programme on BC mortality.

Background. Chronic lymphocytic leukaemia (CLL), the most common form of leukaemia in adults in Western countries, is characterized by the clonal expansion of B cells. Despite major advances in CLL therapy/diagnosis, the medical approach to CLL can be further improved. Here we explore the potential diagnostic/therapeutic role of the elongation factor 1 A (eEF1A) in CLL. Two major isoforms of eEF1A proteins exist: the ubiquitous eEF1A1 and the tissue-specialized eEF1A2. Beside their role in the elongation step of translation, both isoforms are involved in different cellular processes such as cell proliferation and apoptosis. Whereas both eEF1A isoforms play a role in solid and hematologic human tumors, nothing is known in CLL. Methods. eEF1A1/eEF1A2 amounts were quantitated by quantitative real time PCR and western blotting in the lymphocytes of 46 CLL patients vs 26 normal control. eEF1A1 functional role in CLL was investigated in a cellular (MEC-1) and in a subcutaneous xenograft animal model of CLL via its targeting by an aptamer (GT75) or a siRNA (siA1), we previously developed. As control molecules an inactive aptamer (CT75) or siRNA (siGL2) were used. Results. At the mRNA level, eEF1A1 but not eEF1A2 was significantly (p=0,0081) more elevated in CLL lymphocytes compared to control. At the protein level, both eEF1A1 and eEF1A2 were more elevated (p=0,028) in CLL lymphocytes compared to control. Moreover, eEF1A1 but not eEF1A2 protein levels were higher (p=0,0042) in patient which died during the study compared to those surviving. Finally, eEF1A1 targeting by either GT75 or siA1 resulted in MEC-1 viability down regulation (p=0,04) mostly due to autophagy stimulation. In vivo, GT75 or siA1 resulted in tumor growth down-regulation (p=0.014) and extension of animal survival (p=0.014), demonstrating the functional role of eEF1A1 in CLL. Conclusions. The increase of eEF1A1/eEF1A2 protein in lymphocytes of CLL patient cells suggests a role as possible novel CLL markers. The increase of eEF1A1 protein in dead vs surviving patients may confer to eEF1A1 also the role of a novel prognostic marker. This, together with the involvement of eEF1A1 in MEC-1 survival in vitro and in vivo, opens the possibility to consider eEF1A1 also as a novel therapeutic target in CLL.