Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3\u2009cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3\u2009cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT

Longitudinal transcriptomic and genetic landscape of radiotherapy response in canine melanoma

Canine malignant melanoma (MM) is a highly aggressive tumour with a low survival rate and represents an ideal spontaneous model for the human counterpart. Considerable progress has been recently obtained, but the therapeutic success for canine melanoma is still challenging. Little is known about the mechanisms beyond pathogenesis and melanoma development, and the molecular response to radiotherapy has never been explored before. A faster and deeper understanding of cancer mutational processes and developing mechanisms are now possible through next generation sequencing technologies. In this study, we matched whole exome and transcriptome sequencing in four dogs affected by MM at diagnosis and at disease progression to identify possible genetic mechanisms associated with therapy failure. According to previous studies, a genetic similarity between canine MM and its human counterpart was observed. Several somatic mutations were functionally related to MAPK, PI3K/AKT and p53 signalling pathways, but located in genes other than BRAF, RAS and KIT. At disease progression, several mutations were related to therapy effects. Natural killer cell-mediated cytotoxicity and several immune-system-related pathways resulted activated opening a new scenario on the microenvironment in this tumour. In conclusion, this study suggests a potential role of the immune system associated to radiotherapy in canine melanoma, but a larger sample size associated with functional studies are needed

A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.Peer reviewedFinal Published versio

Utilizzo dell’ecografia e della TC nella diagnosi e nel trattamento dei corpi estranei vegetali in 56 cani

.Introduzione e scopo del lavoro- La patologia da corpo estraneo migrante si riscontra frequentemente nei piccoli animali e spesso rappresenta una sfida diagnostica e terapeutica per il medico veterinario. La rimozione del corpo estraneo presuppone la precisa identificazione della sua sede grazie all’utilizzo combinato di diverse tecniche di diagnostica per immagini (radiologia, ecografia, tomografia computerizzata). Il nostro obiettivo è quello di mettere a punto un protocollo diagnostico per il quale nel caso in cui l’ecografia da sola non sia in grado di individuare il corpo estraneo, si possa associare un esame di tomografia computerizzata, che individui la regione dove molto probabilmente esso è localizzato. La guida ecografica intaoperatoria, infine, permette di aumentare la percentuale di successo nell’estrarre i corpi estranei vegetali. Materiali e metodi- Nella prima parte di questo studio, l’utilizzo del solo esame ecografico è stato valutato in modo retrospettivo in un gruppo di 32 cani. La seconda parte, prospettiva, ha coinvolto un gruppo di 24 cani, in cui un precedente esame ecografico e/o esplorazione chirurgica avevano fallito nella identificazione del corpo estraneo. Questi animali sono stati esaminati mediante un protocollo che prevedeva l’associazione di tomografia computerizzata ed ecografia. Risultati- Sono stati confrontati i risultati ottenuti mediante la sola ecografia (identificazione dei corpi estranei in 29/32 casi, accuratezza del 90,6%), con le tecniche combinate (ecografia e tomografia computerizzata - identificazione dei corpi estranei in 24/24 casi, accuratezza del 100%). Si è inoltre valutata l’accuratezza della chirurgia eseguita senza o con guida ecografica. Dei 20 casi operati senza l’ausilio dell’ecografia, in 12 cani sono stati trovati ed asportati uno o più corpi estranei (accuratezza 60%). Nei 36 casi gestiti con ecografia intra-operatoria, sono stati trovati ed asportati i corpi estranei in 35 cani (accuratezza del 97,2%). Discussione- In conclusione, l’ecografia ha evidenziato un’elevata accuratezza diagnostica della patologia da corpo estraneo vegetale. Tuttavia, nei casi più complessi, l’associazione di esame tomografico ed ecografico ha portato un maggiore successo diagnostico. Infine, in questi soggetti l’ausilio della ecografia intra-operatoria ha aumentato la probabilità di trovare ed asportare il corpo estraneo vegetale