Contrast-enhanced ultrasound for sentinel lymph node mapping in the routine staging of canine mast cell tumours: A feasibility study.

Canine mast cell tumours (MCTs) typically spread to lymph nodes (LNs) before reaching distant sites, and LN assessment is an important part of MCT staging. Sentinel LN (SLN) mapping techniques to identify draining LNs are being developed and could improve the accuracy of MCT staging. The primary objective of this feasibility study was to determine the safety and effectiveness of contrast-enhanced ultrasound (CEUS) to identify SLNs. Secondary objectives were to determine if the SLNs identified by CEUS coincided with the regional LN predicted by the anatomical lymphosomes, if previous MCT excision altered CEUS SLN findings, and if CEUS could identify MCT nodal metastases. Between June 2017 and March 2019, 59 dogs with 62 MCTs were enrolled. No adverse events related to CEUS were reported. CEUS detected at least 1 SLN in 59/62 MCTs (95.2%, 95% CI: 86.5-99.0%). In only 32/59 (54.2%) MCTs, clinicians would have correctly predicted the SLN(s) identified by CEUS. Among the 35 MCTs that had histological examination of the SLN(s), the prevalence of metastasis was 60% (95% CI: 42.1-76.1%). Additional staging procedures did not reveal any metastases in dogs with histologically non-metastatic SLNs. Integration of CEUS SLN mapping into the routine staging of MCTs is promising, but future studies are required to refine this procedure and to investigate if it would translate into a clinical benefit.

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer.

Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.

Evaluation of a 0.75 × 109 /L absolute neutrophil count cut-off for antimicrobial prophylaxis in canine cancer chemotherapy patients.

Absolute neutrophil count (ANC) cut-offs for antimicrobial prophylaxis in veterinary cancer chemotherapy patients are empirical and vary between institutions. Evidence based cut-offs are vital for antimicrobial stewardship, particularly as global antimicrobial resistance rises. The primary objectives of this study were to evaluate the tolerability of a <0.75 × 109 /l ANC cut-off for antimicrobial prophylaxis in dogs after receiving chemotherapy and its impact on antimicrobial prescription. Predicted nadir ANCs (pnANCs) were stratified into six groups (<0.75 × 109 /l [receiving antimicrobial prophylaxis], 0.75-0.99 × 109 /l, 1-1.49 × 109 /l, 1.5-1.99 × 109 /l, 2.0-3.59 × 109 /l and 3.6-12 × 109 /l [reference interval]). The incidences of post-nadir febrile neutropenia (FN) and non-haematological toxicity (NHT) were compared between groups. Five hundred and eighty-six pnANCs were recorded for 181 dogs. There were four episodes of post-nadir FN and 90 episodes of post-nadir NHT. There was no significant difference in incidence of post-nadir FN (P = .063) or post-nadir NHT (P = .084) between pnANC groups. Antimicrobial prophylaxis was prescribed following 8.8% of the chemotherapy administrations; had cut-off values of <1.0 × 109 /l or <1.5 × 109 /l been used it would have been prescribed in 15.3% and 25.8% of cases respectively. An ANC cut-off of <0.75 × 109 /l for antimicrobial prophylaxis appears to be well tolerated and minimizes the prescription of antimicrobials.

Somatic evolution and global expansion of an ancient transmissible cancer lineage.

The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

Development and validation of the RQC: a daily contact log for ACT and ICM teams.

AIM: Instruments to measure the process--the daily activities of home care workers--have received little attention and may impede research in refining the active ingredients, the clientele best served and continuous quality improvement. We developed a decade ago in Quebec, Canada, a new daily contact log (relevé quotidien des contacts or RQC) that has now reached in practice 1 million entries. METHODS: Three features distinguish the RQC development, namely, practical ergonomics, a clear logic, and response categories easy to understand and retain. The instrument is filled following any 10-minute or more contact with or about the client, and covers the location, time and actors of the episode of care, and the nature of the intervention (crisis, representing, accompanying, discussing) in 10 areas (i.e. medication, daily living activities, housing, relationships, substance abuse, legal, etc.). Inter-rater agreement for each RQC response category and rater agreement with a criterion measure (coded vignettes) were evaluated. RESULTS: Kappa coefficients and intra-class correlation coefficients yielded results ranging from at least moderate to generally substantial agreement for all 77 response categories. CONCLUSIONS: The new RQC may support international studies of the implementation and application of various forms of intensive home care, refining its indications, and serves as a clinical and managerial tool to ensure quality of the interventions.

Factorial validation of a French short-form of the Working Alliance Inventory.

Evaluation of the therapeutic alliance is crucial for understanding the therapeutic process and its results. However, few instruments are available in French. This article aims to validate a French short form of the Working Alliance Inventory (WAI). Unlike other questionnaires, the WAI is the most widely used in psychotherapy research as well as in social psychiatry. Confirmatory factor analyses were carried out on a sample of 150 client-case manager dyads in order to determine the validity of this short-form instrument. The results of these confirmatory factor analyses allowed us to answer different authors' questions (Horvath and Greenberg, 1989; Tracey and Kokotovic, 1989) regarding the factorial structure of the WAI. The results also indicated a unidimensional solution as being the most valid for the two samples. We suggest that, in future studies, only one score be considered for the evaluation of the WAI. We also suggest modifying two statements in the English and French versions in order to render a faithful comparison between the therapist and client versions.