TRATTAMENTO ABLATIVO CON MICROONDE DI METASTASI EPATICHE DA TUMORE DELLA MAMMELLA: STUDIO DI FATTIBILITÀ ED EFFICACIA

INTRODUCTION Prognosis of patients with breast cancer liver metastases is still dismal. Some retrospective data support adjuvant surgery in selected patients. Ablative treatment in the management of breast cancer liver metastases remains controversial. MATERIAL AND METHODS We evaluated the efficacy (complete ablation and recurrence rate) and the safety (morbidity and mortality) of the microwave ablation treatment (MWA) of breast cancer liver metastases, performed in our Center from 2009 to 2016. Analysis was performed on a nodule-oriented and patient-oriented base. RESULTS Median time to liver metastases development was 52.13 months (IQR 25.5- 81.72), 92.5% of which were metachronous. Forty patients underwent 51 MWA sessions, percutaneously (27 sessions, 33 nodules) and laparoscopically (24 sessions, 67 nodules). Complete ablation rate for nodules ≤2 cm was 95.56% whereas the 3- and 6-months recurrence rate, irrespectively of the nodule dimension, was 12.73% and 26.19%, respectively. MWA was associated with no 90-day mortality. Morbidity rate was 20%. Two patients are alive and free of disease at 49 and 86 months, respectively

TRATTAMENTO ABLATIVO CON MICROONDE DI METASTASI EPATICHE DA TUMORE DELLA MAMMELLA: STUDIO DI FATTIBILITÀ ED EFFICACIA

INTRODUCTION Prognosis of patients with breast cancer liver metastases is still dismal. Some retrospective data support adjuvant surgery in selected patients. Ablative treatment in the management of breast cancer liver metastases remains controversial. MATERIAL AND METHODS We evaluated the efficacy (complete ablation and recurrence rate) and the safety (morbidity and mortality) of the microwave ablation treatment (MWA) of breast cancer liver metastases, performed in our Center from 2009 to 2016. Analysis was performed on a nodule-oriented and patient-oriented base. RESULTS Median time to liver metastases development was 52.13 months (IQR 25.5- 81.72), 92.5% of which were metachronous. Forty patients underwent 51 MWA sessions, percutaneously (27 sessions, 33 nodules) and laparoscopically (24 sessions, 67 nodules). Complete ablation rate for nodules ≤2 cm was 95.56% whereas the 3- and 6-months recurrence rate, irrespectively of the nodule dimension, was 12.73% and 26.19%, respectively. MWA was associated with no 90-day mortality. Morbidity rate was 20%. Two patients are alive and free of disease at 49 and 86 months, respectively.INTRODUZIONE La prognosi delle pazienti con metastasi epatiche da carcinoma mammario è ancora infausta. Alcuni dati retrospettivi suggeriscono un aumento della sopravvivenza nelle pazienti sottoposte a chirurgia adiuvante delle metastasi. Il trattamento ablativo delle metastasi da carcinoma mammario è ancora controverso. MATERIALI E METODI Abbiamo valutato l’efficacia (tasso di ablazione completo e di recidiva) e la sicurezza (morbilità e mortalità) del trattamento ablativo con microonde delle metastasi epatiche, eseguito presso il nostro Centro dal 2009 al 2016. L’analisi è stata condotta sulla base dei noduli e ablati e sulla base delle pazienti trattate. RISULTATI Il 92,5% delle metastasi sono metacrone con un tempo mediano di comparsa dalla diagnosi di tumore della mammella di 52,13 mesi (IQR 25,5- 81,72). Quaranta pazienti sono state sottoposte a 51 sessioni di trattamento ablativo con microonde, percutanea (27 sessioni, 33 noduli) e laparoscopica (24 sessioni, 67 noduli). Il tasso di ablazione completa per noduli ≤2 cm è risultata pari al 95,56% mentre il tasso di recidiva globale a 3 e 6 mesi, indipendentemente dalle dimensioni dei noduli, è stato del 12,73% e del 26,19%, rispettivamente. La mortalità a 90 giorni è stata nulla e il tasso di complicanze è stato del 20%. Due pazienti sono vive e libere da malattia a 49 e 86 mesi

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia