A 20-year scoping review of the veterinary interventional radiology and interventional endoscopy literature (2000-2019).

BACKGROUND: Interventional radiology (IR) and interventional endoscopy (IE) have broad potential for minimally invasive therapy in veterinary patients, but the scope of original peer-reviewed veterinary IR/IE research publications has not been described. OBJECTIVES: Catalogue published applications and indications for noncardiac therapeutic IR/IE in animals and describe type and quality of veterinary IR/IE research over 20 years. METHODS: Highly-cited veterinary journals were searched to identify articles published 2000 to 2019 involving therapeutic IR/IE applications for clinical veterinary patients. Articles were assigned a level of evidence (LOE) according to published standards. Authorship, animal data, study design, and interventions were described. Change in publication rate, study size, and LOE of IR/IE articles over time was analyzed. RESULTS: One hundred fifty-nine of 15 512 (1%) articles were eligible, including 2972 animals. All studies were low LOE and 43% were case reports with ≤5 animals. Number of IR/IE articles per year (P < .001), proportion of journals' articles pertaining to IR/IE (P = .02), and study size (P = .04) all increased over time, but LOE (P = .07) did not. Common target body systems were urinary (40%), digestive (23%) respiratory (20%), and vascular (13%). Common indications were nonvascular luminal obstructions (47%), object retrieval (14%), and congenital anomalies (13%). Most procedures involved indwelling medical devices or embolic agents, whereas tissue resection and other procedures were less common. Procedures utilized fluoroscopy (43%), endoscopy (33%), ultrasound (8%), digital radiography (1%), or fluoroscopy in combination with other modalities (16%). CONCLUSIONS: Treatments involving IR/IE have wide applicability in veterinary medicine but large, rigorous, and comparative studies describing these procedures are lacking.

Pharmacokinetic study comparing doxorubicin concentrations after chemoembolization or intravenous administration in dogs with naturally occurring nonresectable hepatic carcinoma.

BACKGROUND: Chemoembolization is a viable treatment option for patients with nonresectable hepatic carcinoma (HC) and may allow delivery of chemotherapeutic drugs with decreased systemic toxicity. HYPOTHESIS/OBJECTIVE: Compare the serum concentrations of doxorubicin after chemoembolization or IV administration in the same patient. We hypothesized that locoregional delivery may result in increased tumor chemotherapeutic drug concentrations, reflected by decreased measurable serum drug concentrations. Adverse hematological events were hypothesized to be decreased after locoregional delivery. ANIMALS: Seventeen client-owned dogs with incompletely resectable HC. METHODS: Prospective, single-arm clinical trial. Drug-eluting bead transarterial chemoembolization was performed to varying levels of blood flow stasis (NO STASIS, STASIS). Intravenous doxorubicin (IVC) subsequently was administered in selected patients. Systemic exposure was quantified by area under the serum doxorubicin concentration time curve (AUC), maximum serum doxorubicin concentration (Cmax ), and time doxorubicin was last above the limit of quantitation (Tlast ). Nadir test results after treatments were used to evaluate adverse hematological events. RESULTS: Thirteen NO STASIS treatments, 15 STASIS treatments, and 9 IVC treatments were performed. Maximum serum doxorubicin concentration, AUC, and Tlast were significantly lower when comparing NO STASIS or STASIS to IVC treatments. Of the patients with nadir results available, no adverse hematological events were observed after NO STASIS or STASIS treatments. Two patients developed adverse hematological events after IVC treatment. CONCLUSIONS/CLINICAL RELEVANCE: Drug-eluting bead transarterial chemoembolization offers a viable treatment option for patients with incompletely resectable HC with the potential for increased local tumor doxorubicin concentrations, decreased systemic chemotherapeutic exposure, and fewer adverse hematological events.

Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6).

Close homolog of L1 (CHL1) is a cell adhesion molecule of the immunoglobulin superfamily. It promotes neuritogenesis and survival of neurons in vitro. In vivo, CHL1 promotes nervous system development, regeneration after trauma, and synaptic function and plasticity. We identified programmed cell death 6 (PDCD6) as a novel binding partner of the CHL1 intracellular domain (CHL1-ICD). Co-immunoprecipitation, pull-down assay with CHL1-ICD, and proximity ligation in cerebellum and pons of 3-day-old and 6-month-old mice, as well as in cultured cerebellar granule neurons and cortical astrocytes indicate an association between PDCD6 and CHL1. The Ca2+-chelator BAPTA-AM inhibited the association between CHL1 and PDCD6. The treatment of cerebellar granule neurons with a cell-penetrating peptide comprising the cell surface proximal 30 N-terminal amino acids of CHL1-ICD inhibited the association between CHL1 and PDCD6 and PDCD6- and CHL1-triggered neuronal survival. These results suggest that PDCD6 contributes to CHL1 functions in the nervous system.

Adherence to follow-up recommendations for dogs with apocrine gland anal sac adenocarcinoma: A multicentre retrospective study.

Progressive disease is common following anal sacculectomy for apocrine gland anal sac adenocarcinoma (AGASACA); additional therapy may prolong survival. Adherence to medical recommendations influences therapeutic success in humans. The purpose of this study was to assess the adherence to follow-up recommendations in dogs with AGASACA. Medical records of patients that underwent anal sacculectomy for AGASACA, with or without iliosacral lymphadenectomy, between July 2015 and July 2018, were reviewed at eight referral institutions to assess post-operative recommendations and owner adherence to recommendations. One hundred and seventy-four dogs were included, of which 162 underwent unilateral anal sacculectomy, 12 underwent bilateral anal sacculectomy and 39 underwent concurrent iliosacral lymphadenectomy. Seventy-six owners (44%) received recommendations for staging at the time of discharge, histopathology results or at the first follow-up visit. One hundred and forty owners (80%) received recommendations for treatment following the initial surgery. Fifty of seventy-six (66%) owners pursued at least one staging recommendation and 69 of 140 (49%) owners pursued some kind of adjuvant treatment recommendation. Overall, 16 of 76 (21%) were adherent to staging recommendations with 20 adherent for the first year following surgery (26%). Forty-seven of 140 (34%) were adherent to treatment recommendations with 54 (39%) adherent for the first year. Owners that were adherent to restaging recommendations at 1 year following surgery were significantly more likely to pursue treatment for progressive disease (P = .014). Further work is required to assess owner motivation and evaluate strategies to improve adherence, given the potential impact on patient treatment.

ΔNp63-driven recruitment of myeloid-derived suppressor cells promotes metastasis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is particularly aggressive, with enhanced incidence of tumor relapse, resistance to chemotherapy, and metastases. As the mechanistic basis for this aggressive phenotype is unclear, treatment options are limited. Here, we showed an increased population of myeloid-derived immunosuppressor cells (MDSCs) in TNBC patients compared with non-TNBC patients. We found that high levels of the transcription factor ΔNp63 correlate with an increased number of MDSCs in basal TNBC patients, and that ΔNp63 promotes tumor growth, progression, and metastasis in human and mouse TNBC cells. Furthermore, we showed that MDSC recruitment to the primary tumor and metastatic sites occurs via direct ΔNp63-dependent activation of the chemokines CXCL2 and CCL22. CXCR2/CCR4 inhibitors reduced MDSC recruitment, angiogenesis, and metastasis, highlighting a novel treatment option for this subset of TNBC patients. Finally, we found that MDSCs secrete prometastatic factors such as MMP9 and chitinase 3-like 1 to promote TNBC cancer stem cell function, thereby identifying a nonimmunologic role for MDSCs in promoting TNBC progression. These findings identify a unique crosstalk between ΔNp63+ TNBC cells and MDSCs that promotes tumor progression and metastasis, which could be exploited in future combined immunotherapy/chemotherapy strategies for TNBC patients.

Images as tools. On visual epistemic practices in the biological sciences.

Contemporary visual epistemic practices in the biological sciences raise new questions of how to transform an iconic data measurements into images, and how the process of an imaging technique may change the material it is 'depicting'. This case-oriented study investigates microscopic imagery, which is used by system and synthetic biologists alike. The core argument is developed around the analysis of two recent methods, developed between 2003 and 2006: localization microscopy and photo-induced cell death. Far from functioning merely as illustrations of work done by other means, images can be determined as tools for discovery in their own right and as objects of investigation. Both methods deploy different constellations of intended and unintended interactions between visual appearance and underlying biological materiality. To characterize these new ways of interaction, the article introduces the notions of 'operational images' and 'operational agency'. Despite all their novelty, operational images are still subject to conventions of seeing and depicting: Phenomena emerging with the new method of localization microscopy have to be designed according to image traditions of older, conventional fluorescence microscopy to function properly as devices for communication between physicists and biologists. The article emerged from a laboratory study based on interviews conducted with researchers from the Kirchhoff-Institute for Physics and German Cancer Research Center (DKFZ) at Bioquant, Heidelberg, in 2011.