β3-Adrenoreceptor Blockade Induces Stem Cells Differentiation in Melanoma Microenvironment

Although there is an increasing evidence that cancer stem cell (CSC) niches in the tumor microenvironment (TME) plays a crucial role in sustaining solid tumors progression, several molecular players involved in this regulation still remain unknown. The role of β-adrenergic signaling in enhancing tumor growth through β2-adrenoreceptors (β2-ARs) has been confirmed in different cancer models, but the role played by the β3-adrenergic receptor (β3-AR) has recently emerged. Previous studies showed that β3-AR promotes cancer growth through the activation of different stromal cells in the TME, and leads to melanoma malignancy progression through inflammation, angiogenesis, and immunotolerance. Here we show that in B16 melanoma-bearing mice, the pharmacological β3-AR blockade is able to reduce the expression of CSC markers, and to induce a differentiated phenotype of hematopoietic subpopulations in TME. In particular, cytofluorimetric analysis (FACS) of the tumor mass shows that β3-AR antagonist SR59230A promotes hematopoietic differentiation as indicated by increased ratios of lymphoid/hematopoietic stem cells (HSCs) and of myeloid progenitor cells/HSCs, and increases the number of Ter119 and natural killer (NK) precursor cells, and of granulocyte precursors, indicating active hematopoiesis within the tumor tissue. Moreover, pharmacological antagonism of β3-AR induces mesenchymal stem cell (MSC) differentiation into adipocytes subtracting a potential renewal of the stem compartment by these cells. Here we demonstrate that β3-AR blockade in the TME by inducing the differentiation of different stromal cells at the expense of stemness traits could possibly have a favorable effect on the control of melanoma progression

Superfici di rivestimento per ridurre il tasso d’infezione dopo impianto di megaprotesi

Sono descritte le nuove tecnologie di trattamento delle superfici protesiche per contrastare la formazione del biofilm batterico. Sono suddivise in quattro classi: 1) rivestimenti antibiotati; 2) rivestimenti con sostanze anti settiche; 3) rivestimenti a dismissione di ioni metallici; 4) rivestimenti con adsorbimento sostanze organiche e non ad azione antibatterica. Vengono riportati i risultati delle prime sperimentazioni cliniche soprattutto incoraggianti nei rivestimenti con argento attivo e viene riportata l’incidenza delle complicazioni e delle possibili tossicità locali e generali

Consensus on COVID‐19 Vaccination in Pediatric Oncohematological Patients, on Behalf of Infectious Working Group of Italian Association of Pediatric Hematology Oncology

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS‐CoV‐2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS‐CoV‐2 infection and disease (COVID‐19) in the pediatric subjects; COVID‐19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID‐19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID‐19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID‐ 19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays

Osteoarticular allografts in paediatric bone tumor reconstruction of the knee

Osteoarticular allografts represent a reconstructive option after bone tumor resection around the knee in growing children. The major advantage is the chance to preserve the growth plate of the remaining bone, but the disadvantage is the high failure rate eventually requiring definitive prosthetic replacement at skeletal maturity. We retrospectively reviewed 22 patients who underwent osteoarticular allograft reconstructions of the distal femur (16) or proximal tibia (6). There were 12 females and 10 males with an average age at surgery of 11 years (7-15). The diagnosis was osteosarcoma in 19 cases and Ewing sarcoma in 3. All patients underwent pre- and post-operative chemotherapy. At an average follow-up of 103 months (12-167), 18 patients (82%) were alive and 4 had died (18%). We observed 10 allograft failures requiring prosthetic replacement, 6 in distal femur and 4 in proximal tibia reconstructions. At last follow-up 8 allografts (36%) were still in place. Overall allograft survival was 79.6% at five and 45.8% at ten years. In distal femur, allograft survival was 86.2% at five and 59.1% at ten years. In proximal tibia, allograft survival was 62.5% at 5 years and 31.2% at 67 months. Average limb shortening was 3 cm (0- 5) in 8 patients with the allograft still in situ and 2 cm (0-4) in 10 patients after prosthetic replacement. Average MSTS functional score of the whole series was 25 (83.7%). The MSTS score of patients after revision with prosthetic replacement was 24 (80%) while patients who still had the allograft retained had an average MSTS scores of 26.8 (89.3%). In conclusion, osteoarticular allograft reconstruction of the knee after bone tumor resection in pediatric age can be considered a temporary solution with the aim to limit limb length discrepancy before definitive prosthetic replacement after skeletal maturity

Mucormicosi invasiva documentata in pazienti oncoematologici pediatrici: studio retrospettivo del gruppo di lavoro AIEOP.

Studio retroepttivo sulle infezioni da Mucor in pazienti pediatrici oncologic

Guidelines on Vaccinations in Pediatric Haematology and Oncology Patients

Objective:Vaccinations are the most important tool to prevent infectious diseases. Chemotherapy-induced immune depression may impact the efficacy of vaccinations in children. PATIENTS AND METHODS: A panel of experts of the supportive care working group of the Italian Association Paediatric Haematology Oncology (AIEOP) addressed this issue by guidelines on vaccinations in paediatric cancer patients. The literature published between 1980 and 2013 was reviewed. RESULTS AND CONCLUSION: During intensive chemotherapy, vaccination turned out to be effective for hepatitis A and B, whilst vaccinations with toxoid, protein subunits, or bacterial antigens should be postponed to the less intensive phases, to achieve an adequate immune response. Apart from varicella, the administration of live-attenuated-virus vaccines is not recommended during this phase. Family members should remain on recommended vaccination schedules, including toxoid, inactivated vaccine (also poliomyelitis), and live-attenuated vaccines (varicella, measles, mumps, and rubella). By the time of completion of chemotherapy, insufficient serum antibody levels for vaccine-preventable diseases have been reported, while immunological memory appears to be preserved. Once immunological recovery is completed, usually after 6 months, response to booster or vaccination is generally good and allows patients to be protected and also to contribute to herd immunity

Sarcoma di Ewing del bacino: risultati oncologici dopo trattamento multidisciplinare

Introduzione: Lo scopo del nostro studio è stato quello di valutare retrospettivamente una serie consecutiva di 21 pazienti affetti da sarcoma di Ewing al bacino con l’obiettivo di valutare controllo locale, sistemico e la correlazione con il trattamento multidisciplinare. Materiali e Metodi: Tra il 2000 e il 2016, 21 pazienti affetti da sarcoma di Ewing localizzato al bacino sono stati trattati nel nostro istituto (età media 19, range 9-43; M/F: 12/9). Tre pazienti hanno ricevuto radioterapia senza intervento chirurgico e 18 pazienti sono stati sottoposti a resezione di bacino (7 senza radioterapia, 7 con rioterapia pre-operatoria, 4 con radioterapia postoperatoria). I margini sono stati ampi in 16 e marginali in 2 casi. In 5 casi non è stata eseguita alcuna ricostruzione mentre in 12 casi la ricostruzione è avvenuta con innesti massivi + protesi, in un caso è stata eseguita un’artrodesi ischiofemorale dopo resezione. Risultati: Il follow-up medio è stato di 36 mesi (range 3-156). Sette pazienti (33%) sono liberi da malattia all’ultimo follow-up. Undici pazienti (53%) sono deceduti per progressione di malattia dopo una media di 15,7 mesi (range 3-32). Tre pazienti (14%) non hanno presentato alcuna evidenza di malattia dopo il tratta-mento delle metastasi polmonari. Le complicanze postoperatorie osservate sono state: 2 lussazioni della protesi di anca, una infezione superficiale e 5 infezioni profonde (6/18, 33%). Due pazienti (5%) hanno avuto una recidiva locale e il 57% dei pazienti ha sviluppato metastasi. La sopravvivenza globale è stata del 44,4% a 5 anni. Discussione: Il trattamento multidisciplinare del Sarcoma di Ewing include la chemioterapia seguita della chirurgica e/o radioterapia. Il trattamento delle localizzazioni pelviche è ancora dibattuto, riguardo la scelta tra chirurgia, radioterapia e il timing in caso di associazione. Conclusioni: Nonostante il trattamento multidisciplinare avanzato, il sarcoma di Ewing localizzato al bacino rimane una sfida nell’oncologia ortopedica con alto rischio di progressione sistemica e bassa sopravvivenza globale. Le ricostruzioni di bacino e la RT perioperatoria aumentano il rischio di complicanze postoperatorie