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To evaluate the advantages of dual-energy computed tomography (DECT) virtual non-hydroxyapatite color mapping (VNHAP) in combination with standard bone CT (BCT) in the identification of subtle or occult traumatic fractures referred to emergency and acceptance departments (DEAs). Forty patients (22 men; mean age 83 ± 23.7 y) with suspected traumatic fractures referred to our emergency department and examined with a fast kilovoltage-switching single-source spectral CT scan between January and October 2023 were retrospectively reviewed. The BCT and VNHAP images were blindly evaluated by two radiologists with >10 years and <2 years of experience in musculoskeletal imaging. Both techniques were evaluated in terms of sensitivity (SE), specificity (SP), positive and negative predictive values (PPVs and NPVs) and accuracy for fracture detection, as confirmed at a 3-month clinical–instrumental follow-up. Inter-observer agreement and examination times were also analyzed. Fractures were confirmed in 18/40 cases. The highest values of diagnostic performance for VNHAP images were obtained in terms of SP (90.9% and 95%) and PPV (87.5% and 92.8%) and for the less experienced operator. No statistically significant differences were observed between the diagnostic accuracy of the two readers in the evaluation of VNHAP images. Inter-observer agreement was moderate (κ = 0.536) for BCT and substantial (κ = 0.680) for VNHAP. Comparing the two operators, a significantly longer examination time for BCT and no significant difference for VNHAP were registered. Our preliminary experience may encourage the employment of VNHAP maps in combination with BCT images in emergency settings. Their use could be time-saving and valuable in terms of diagnostic performance, especially for less experienced operators. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody‐drug conjugate (ADC) therapy. Methods: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT‐PCR, Western Blot analysis, and ELISA. Results: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer‐derived extracellular vesicles. Moreover, LGALS3BP high‐expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC‐payload DM4, with an IC50 around 0.3 nM. Conclusions: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC‐based therapy. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. Materials and Methods: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. Results: Cases harbouring high‐risk‐of‐death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild‐type cases, while no significant difference in treatment outcomes was found between cases with low‐risk‐of‐death mutations and wild‐type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. Conclusions: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients. [ABSTRACT FROM AUTHOR]

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone. [ABSTRACT FROM AUTHOR]

Background: Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. Aims: The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. Materials & Methods: TB was evaluated on hematoxylin and eosin‐stained sections in the hotspot area of the infiltrative front (×200‐magnification). It was scored using a two‐tier system, a three‐tier system, and according to BD‐model and revised‐Grading system. Univariate and multivariate Cox regression analyses of disease‐specific survival (DSS) and disease‐free survival (DFS) were performed. A p < 0.05 was considered as statistically significant. Results: The two‐tier and three‐tier systems resulted an independent prognostic factor of DSS. High‐risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low‐risk group. It is significantly increased even for intermediate‐risk group. No significant differences emerged classifying patients according to BD‐model and revised‐Grading system. Discussion: These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5‐bud cutoff significantly discriminates their outcomes. Conclusion: Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker. [ABSTRACT FROM AUTHOR]

Background: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor–Node–Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. Methods: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni‐/multifocal and as intra‐/peritumoral. Disease‐Specific and Relapse‐Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. Results: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph–node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p‐value = 0.008). Moreover, patients exhibiting both multifocal intra‐ and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p‐value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. Conclusions: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm. [ABSTRACT FROM AUTHOR]