Tumor induced osteomalacia: a systematic review and individual patient's data analysis

Context: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far. Evidence acquisition: On 06/26/2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia", "oncogenic osteomalacia", "hypophosphatemia". There were no language restrictions. This review was performed according to PRISMA criteria. Evidence results: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared to TIO women. The TIO causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO causing neoplasms were equally located in bone and soft tissues; these latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in >90% of patients). Promising non-surgical therapies are treatments with burosumab in TIO patients with elevated Fibroblast Growth Factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques. Conclusion: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located to soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising non-surgical therapies

Rare chondrosarcoma of the breast treated with quadrantectomy instead of mastectomy. A case report

Breast chondrosarcoma is a rare sarcoma that mainly occurs in females >50 years old. To the best of our knowledge, only 16 cases were reported in the literature prior to 2013 and all patients were surgically treated by mastectomy, with or without lymphadenectomy, which was occasionally preceded by neoadjuvant chemotherapy. However, the literature does not report the benefit of mastectomy compared with a more conservative surgery. The present study reports a novel case of extraskeletal chondrosarcoma of the breast. A 63‑year‑old female patient presented with a neoplasm localized in the upper‑outer quadrant of the right breast. The palpable lesion with sharp margins was a firm parenchymatous mass, which was confirmed by ultrasonography and mammography. The patient underwent conservative quadrantectomy instead of mastectomy, followed by post‑surgical chemotherapy. A positron emission tomography scan performed five months subsequent to the surgery revealed no remnants of the disease. The patient underwent a strict clinical and instrumental follow‑up, and two and half years after surgery, there are no signs of recurrent disease. In conclusion, the present case is currently one of the two cases in which a more conservative quadrantectomy was performed, instead of mastectomy. This surgical approach did not lead to metastasis and resulted in a good follow‑up for the patient

Translationally controlled tumor protein in prostatic adenocarcinoma: correlation with tumor grading and treatment-related changes

12Prostate cancer is the second leading cause of cancer-related death. The androgen deprivation therapy is the standard treatment for advanced stages. Unfortunately, virtually all tumors become resistant to androgen withdrawal. The progression to castration-resistance is not fully understood, although a recent paper has suggested translationally controlled tumor protein to be implicated in the process. The present study was designed to investigate the role of this protein in prostate cancer, focusing on the correlation between its expression level with tumor differentiation and response to treatment. We retrieved 292 prostatic cancer specimens; of these 153 had been treated only by radical prostatectomy and 139 had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade therapy. Non-neoplastic controls were represented by 102 prostatic peripheral zone specimens. In untreated patients, the expression of the protein, evaluated by RT-qPCR and immunohistochemistry, was significantly higher in tumor specimens than in non-neoplastic control, increasing as Gleason pattern and score progressed. In treated prostates, the staining was correlated with the response to treatment. An association between protein expression and the main clinicopathological factors involved in prostate cancer aggressiveness was identified. These findings suggest that the protein may be a promising prognostic factor and a target for therapy.openopenRocca, Bruno Jim; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; De Falco, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; Del Vecchio, Maria Teresa; Ambrosio, Maria Raffaella; Tosi, PieroRocca, BRUNO JIM; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; DE FALCO, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; DEL VECCHIO, MARIA TERESA; Ambrosio, MARIA RAFFAELLA; Tosi, Pier

17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor–positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7’s miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17β-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086)

Background The management of melanoma patients with metastatic melanoma in the sentinel nodes (SN) is evolving based on the results of trials questioning the impact of completion lymph node dissection (CLND) and demonstrating the efficacy of new adjuvant treatments. In this landscape, new prognostic tools for fine risk stratification are eagerly sought to optimize the therapeutic path of these patients. Methods A retrospective cohort of 2,086 patients treated with CLND after a positive SN biopsy in thirteen Italian Melanoma Centers was reviewed. Overall survival (OS) was the outcome of interest; included independent variables were the following: age, gender, primary melanoma site, Breslow thickness, ulceration, sentinel node tumor burden (SNTB), number of positive SN, non-sentinel lymph nodes (NSN) status. Univariate and multivariate survival analyses were performed using the Cox proportional hazard regression model. Results The 3-year, 5-year and 10-year OS rates were 79%, 70% and 54%, respectively. At univariate analysis, all variables, except for primary melanoma body site, were found to be statistically significant prognostic factors. Multivariate Cox regression analysis indicated that older age (P < 0.0001), male gender (P = 0.04), increasing Breslow thickness (P < 0.0001), presence of ulceration (P = 0.004), SNTB size (P < 0.0001) and metastatic NSN (P < 0.0001) were independent negative predictors of OS. Conclusion The above results were utilized to build a nomogram in order to ease the practical implementation of our prognostic model, which might improve treatment personalization

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

T-REX OU4 HIRES: the high resolution spectrograph for the E-ELT

The goal of this unit was to consolidate the project for the construction of the high resolution spectrometer of the E-ELT (HIRES). The task included the development of scientific cases and tools to predict the instrumental performances. From the technical point of view it included several R&D activities in collaboration with highly specialized Italian companies; it culminated with the detailed design of a highly modular instrument based on well established technologies. From the management point of view it lead to the consolidation of a large international consortium that spans over 12 countries and includes most of the European and ESO-related institutes interested in high resolution spectroscopy. This consortium is led by INAF; its formal creation is awaiting the official call by ESO for the phase-A study for the HIRES instrument of the E-ELT

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation