The Society of Thoracic Surgeons Expert Consensus Document on the Management of Pleural Drains following Pulmonary Lobectomy.

The Society of Thoracic Surgeons Workforce on Evidence Based Surgery provides this document on management of pleural drains following pulmonary lobectomy. The goal of this consensus document is to provide guidance regarding pleural drains in five specific areas: 1) choice of drain including size, type, and number, 2) management including use of suction versus water seal and criteria for removal, 3) imaging recommendations including the use of daily and post-pull chest x-rays, 4) use of digital drainage systems and 5) management of prolonged air leak. To formulate the consensus statements a task force of 15 general thoracic surgeons were invited to review the existing literature on this topic. Consensus was obtained using a modified Delphi method consisting of two rounds of voting until 75% agreement on the statements was reached. A total of thirteen consensus statements are provided to encourage standardization and stimulate additional research in this important area.

Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.

BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product. METHODS: Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach. RESULTS: Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment. CONCLUSIONS: Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

Normal variation of clinical mobility of the mandibular symphysis in cats.

Introduction: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in cats and possible associations with bodyweight, age, sex, sexual status, breed and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were evaluated. Materials and methods: Two hundred and sixteen cats of 15 different breeds that underwent maxillofacial, oral and dental procedures from April 2015 to December 2021 were included. Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified on the occlusal radiographic view of the rostral mandibles as fused or open, and with parallel or divergent margins. Results: Bodyweight ranged from 2.2 to 12.5 kg (median 4.0 kg), age from 4 months to 17 years and 4 months (median 6 years and 4 months). At the first evaluation DV symphyseal mobility was 0 in 177 cases (82%), 1 in 32 cases (14.8%) and 2 in 7 cases (3.2%), LM mobility was 0 in 61 cases (28.3%), 1 in 110 cases (50.9%) and 2 in 45 cases (20.8%). 81.1% of the radiographs were included in the statistical analysis. Three symphyses (1.6%) were classified as fused and 190 (98.4%) as open, 129 (68.8%) having divergent margins and 61 (31.6%) parallel. One hundred and forty-eight cases (76.7%) did not show the presence of odontoclastic replacement resorption on the canine teeth (TR subgroup 1), 23 (11.9%) showed stage ≤3 lesions (TR subgroup 2) and 22 (11.4%) stage 4 lesions (TR subgroup 3). Logistic regression models exploring factors that affected DV and LM mobility were statistically significant (p < 0.0001; p < 0.0001) with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in DV mobility was associated with an increase in age and in having resorptive lesions. A decrease in LM symphyseal mobility was associated with being brachycephalic. Conclusion: The great majority of cases showed some degree of LM symphyseal mobility, and 18% showed DV mobility. Symphyseal bony fusion is rare but possible.

Treatment of retroperitoneal sarcoma results in improved outcomes.

OBJECTIVE: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance. ANIMALS: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space. METHODS: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed to report descriptive data for all cases and overall survival time. Multivariate analysis was utilized to evaluate prognostic factors for overall survival. RESULTS: Hemangiosarcoma was the most common histologic subtype diagnosed (76.1%). Cytoreductive and curative intent surgical excision of the RPS was attempted in 12 and 22 dogs, respectively; 12 dogs underwent no surgery or had an exploratory laparotomy with incisional biopsy only. Nineteen dogs received adjuvant chemotherapy, either injectable or metronomic, and 1 dog received adjuvant radiation therapy. Fourteen of the 34 (41.2%) surgically treated dogs developed evidence of local recurrence, but there was no difference in local recurrence when comparing dogs categorized as curative intent versus cytoreductive surgery. The median overall survival time was 238 days. On multivariable analysis, treatment approach was associated with survival with surgical excision (vs palliative treatment) and adjuvant chemotherapy following surgery being protective against death. A diagnosis of hemangiosarcoma was associated with a greater hazard of death. CLINICAL RELEVANCE: This study demonstrates a substantially greater survival time than previously published and suggests a survival benefit from surgical excision and adjuvant chemotherapy.

Improved characterization and translation of NK cells for canine immunotherapy.

The field of cancer immunology has seen a meteoric rise in interest and application due to the discovery of immunotherapies that target immune cells, often leading to dramatic anti-tumor effects. However, successful cellular immunotherapy for solid tumors remains a challenge, and the application of immunotherapy to dogs with naturally occurring cancers has emerged as a high yield large animal model to bridge the bench-to-bedside challenges of immunotherapies, including those based on natural killer (NK) cells. Here, we review recent developments in the characterization and understanding of canine NK cells, a critical springboard for future translational NK immunotherapy research. The characterization of canine NK cells is exceptionally pertinent given the ongoing challenges in defining them and contextualizing their similarities and differences compared to human and murine NK cells compounded by the limited availability of validated canine specific reagents. Additionally, we summarize the current landscape of the clinical and translational literature employing strategies to capitalize on endogenous and exogenous NK cell immunotherapy in canine cancer patients. The insights regarding efficacy and immune correlates from these trials provide a solid foundation to design and test novel combinational therapies to enhance NK cell activity with the added benefit of motivating comparative work to translate these findings to human cancers with extensive similarities to their canine counterparts. The compilation of knowledge from basic canine NK phenotype and function to applications in first-in-dog clinical trials will support the canine cancer model and enhance translational work to improve cancer outcomes for both dogs and humans.

A variant in the 5'UTR of ERBB4 is associated with lifespan in Golden Retrievers.

Genome-wide association studies (GWAS) in long-lived human populations have led to identification of variants associated with Alzheimer's disease and cardiovascular disease, the latter being the most common cause of mortality in people worldwide. In contrast, naturally occurring cancer represents the leading cause of death in pet dogs, and specific breeds like the Golden Retriever (GR) carry up to a 65% cancer-related death rate. We hypothesized that GWAS of long-lived GRs might lead to the identification of genetic variants capable of modifying longevity within this cancer-predisposed breed. A GWAS was performed comparing GR dogs ≥ 14 years to dogs dying prior to age 12 which revealed a significant association to ERBB4, the only member of the epidermal growth factor receptor family capable of serving as both a tumor suppressor gene and an oncogene. No coding variants were identified, however, distinct haplotypes in the 5'UTR were associated with reduced lifespan in two separate populations of GR dogs. When all GR dogs were analyzed together (n = 304), the presence of haplotype 3 was associated with shorter survival (11.8 years vs. 12.8 years, p = 0.024). GRs homozygous for haplotype 3 had the shortest survival, and GRs homozygous for haplotype 1 had the longest survival (11.6 years vs. 13.5 years, p = 0.0008). Sub-analyses revealed that the difference in lifespan for GRs carrying at least 1 copy of haplotype 3 was specific to female dogs (p = 0.009), whereas survival remained significantly different in both male and female GRs homozygous for haplotype 1 or haplotype 3 (p = 0.026 and p = 0.009, respectively). Taken together, these findings implicate a potential role for ERBB4 in GR longevity and provide evidence that within-breed canine lifespan studies could serve as a mechanism to identify favorable or disease-modifying variants important to the axis of aging and cancer.

Normal variation of clinical mobility of the mandibular symphysis in dogs.

Introduction: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in dogs, and evaluate possible associations with breed, bodyweight, age, sex, and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were also evaluated. Methods: Medical records of dogs that underwent anesthetic procedures for maxillofacial, oral and dental evaluation from April 2015 to December 2021 were included. Results: 567 dogs of 95 different breeds were included, with a total of 695 evaluations. Body weight ranged from 0.8 kg to 79 kg (median 14.4 kg) and age from 3 months to 16 years and 4 months (median 6 years and 9 months). Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale, in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified as being fused or open. The open symphyses were further radiographically divided in having parallel or divergent margins. At the time of the first evaluation DV mobility was 0 in 551 cases (97.2%) and 1 in 16 cases (2.8%). LM mobility was 0 in 401 cases (70.7%), 1 in 148 cases (26.1%) and 2 in 18 cases (3.2%). There was not a significant change in mobility over time for cases examined more than once (P= 0.76). All cases had an intraoral radiographic examination. 83.8% of the radiographs were included in the statistical analysis. Two symphyses (0.4%) were classified as fused and 473 (99.6%) as open, 355 (74.7%) having divergent margins and 118 (24.8%) parallel margins. Logistic regression models exploring factors that affected DV and LM mobility were statistically significant (P < 0.0001; P < 0.0001), with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in age and in bodyweight was associated with a decrease in mobility. There was no statistical difference in clinical mobility across specific breeds or sexes. Increased probability of a divergent symphysis and increased DV mobility was found to be associated with a brachycephalic conformation. The increase in LM mobility was comparatively higher in small brachycephalic breeds compared with larger brachycephalic breed. Discussion: The majority of the cases showed little to no mobility of the mandibular symphysis and radiographically bony fusion can be rarely seen.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Training and validation of a novel non-invasive imaging system for ruling out malignancy in canine subcutaneous and cutaneous masses using machine learning in 664 masses.

Objective: To train and validate the use of a novel artificial intelligence-based thermal imaging system as a screening tool to rule out malignancy in cutaneous and subcutaneous masses in dogs. Animals: Training study: 147 client-owned dogs with 233 masses. Validation Study: 299 client-owned dogs with 525 masses. Cytology was non-diagnostic in 94 masses, resulting in 431 masses from 248 dogs with diagnostic samples. Procedures: The prospective studies were conducted between June 2020 and July 2022. During the scan, each mass and its adjacent healthy tissue was heated by a high-power Light-Emitting Diode. The tissue temperature was recorded by the device and consequently analyzed using a supervised machine learning algorithm to determine whether the mass required further investigation. The first study was performed to collect data to train the algorithm. The second study validated the algorithm, as the real-time device predictions were compared to the cytology and/or biopsy results. Results: The results for the validation study were that the device correctly classified 45 out of 53 malignant masses and 253 out of 378 benign masses (sensitivity = 85% and specificity = 67%). The negative predictive value of the system (i.e., percent of benign masses identified as benign) was 97%. Clinical relevance: The results demonstrate that this novel system could be used as a decision-support tool at the point of care, enabling clinicians to differentiate between benign lesions and those requiring further diagnostics.

Changes in diet and supplement use in dogs with cancer.

BACKGROUND: Many dog owners alter their dog's nutritional regimen after a diagnosis of cancer. There are limited data as to specific changes made and reasons behind these changes. HYPOTHESIS/OBJECTIVES: To collect updated and detailed data on changes made by owners to their dog's diet and supplements after a cancer diagnosis. ANIMALS: Responses were collected from a survey of dog owners who brought their dogs to the UC Davis Veterinary Medical Teaching Hospital's Oncology Service for the first time after a cancer diagnosis. Dogs with recurrence or presenting for a second type of cancer were excluded. METHODS: Eligible owners were surveyed between December 2020 and March 2022. The survey contained 62 questions regarding diet, supplement use, and treats, and how these were altered after a cancer diagnosis. Responses were matched to medical record data. RESULTS: One hundred twenty-eight surveys were retained for analysis, including 120 respondents that completed the survey. In response to a cancer diagnosis, 54.8% (95% CI; 45.7%-63.8%) of owners altered diets or supplements or both. The most common informational resource for dog diets was veterinarians (53.9%). Usage of home-prepared foods significantly increased after a cancer diagnosis (P = .03). There was no significant difference in commercial diet usage before or after a diagnosis (P = .25). Joint support products were the most common supplements given both before (37.4%) and after (35.0%) diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Many dog owners alter their dog's nutritional intake after a cancer diagnosis. These owners should be provided information relating to commonly observed alterations, including home-prepared foods and supplements.

ACVR and ECVDI consensus statement: Reporting elements for toxicity criteria of the veterinary radiation therapy oncology group v2.0.

The toxicity criteria of the veterinary radiation therapy oncology group (VRTOG) version 2 guidelines are a substantial update to reflect significant advances in radiation oncology over the last three decades. Radiation therapy techniques provide precise and spatially accurate radiation delivery, which facilitates treating tumors in more anatomic locations and incorporating hypofractionated protocols. The purpose of this update is to aid radiation oncology teams in capturing and grading clinically relevant data that impacts the decision-making process in everyday practice and the assessment of clinical trials involving radiation therapy. A dedicated committee initially updated the criteria to include more anatomical sites and grades to characterize a broad spectrum of possible radiation-induced acute and late tissue changes. Through the revision process, which solicited and incorporated feedback from all radiation oncologists within the American College of Veterinary Radiology (ACVR) and specialists outside the ACVR, the authors endeavored to create a grading structure reflective of clinical decision-making in daily radiation oncology. The updated VRTOG v2 toxicity criteria guideline complements the updated Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) guidelines. Because radiation oncology continues to progress rapidly, the VRTOG toxicity criteria should be regularly updated as adverse event data that will be collected following this update further informs the practice of radiation oncology.

Conventionally fractionated radiation therapy is associated with long-term survival in dogs with infiltrative lipomas.

OBJECTIVE: To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data. ANIMALS: 24 dogs from 2000 to 2020. METHODS: In this retrospective study, dogs received 1 to 3 surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions. RESULTS: Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days [range, 741 to 1,870 days]), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female. CLINICAL RELEVANCE: This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

A pilot study for a non-invasive system for detection of malignancy in canine subcutaneous and cutaneous masses using machine learning.

Introduction: Early diagnosis of cancer enhances treatment planning and improves prognosis. Many masses presenting to veterinary clinics are difficult to diagnose without using invasive, time-consuming, and costly tests. Our objective was to perform a preliminary proof-of-concept for the HT Vista device, a novel artificial intelligence-based thermal imaging system, developed and designed to differentiate benign from malignant, cutaneous and subcutaneous masses in dogs. Methods: Forty-five dogs with a total of 69 masses were recruited. Each mass was clipped and heated by the HT Vista device. The heat emitted by the mass and its adjacent healthy tissue was automatically recorded using a built-in thermal camera. The thermal data from both areas were subsequently analyzed using an Artificial Intelligence algorithm. Cytology and/or biopsy results were later compared to the results obtained from the HT Vista system and used to train the algorithm. Validation was done using a "Leave One Out" cross-validation to determine the algorithm's performance. Results: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the system were 90%, 93%, 88%, 83%, and 95%, respectively for all masses. Conclusion: We propose that this novel system, with further development, could be used to provide a decision-support tool enabling clinicians to differentiate between benign lesions and those requiring additional diagnostics. Our study also provides a proof-of-concept for ongoing prospective trials for cancer diagnosis using advanced thermodynamics and machine learning procedures in companion dogs.

Kinetic Evaluation of the Hypoxia Radiotracers [18F]FMISO and [18F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Purpose: We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors. Methods: Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMRmax) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMRmax was compared with radiotracer trapping rate (k 3), influx rate (K i), and distribution volume (V T). Results: Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMRmax was strongly correlated with the irreversible parameters (k 3 and K i) for [18F]FMISO at > 90 min and with the reversible parameter (V T) for [18F]FAZA at > 120 min. Conclusions: Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMRmax over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMRmax) is a good alternative to quantify tumor hypoxia. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00780-4.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study: Outcomes and risk factors of conversion during minimally invasive lobectomy.

OBJECTIVE: Conversion to thoracotomy continues to be a concern during minimally invasive lobectomy. The aim of this propensity-matched cohort study is to analyze the outcomes and risk factors of intraoperative conversion during video-assisted thoracoscopic surgery (VATS) and robotic lobectomy (RL). METHODS: Data from consecutive lobectomy cases performed for clinical stage IA to IIIA lung cancer was retrospectively collected from the Pulmonary Open, Robotic, and Thoracoscopic Lobectomy study consortium of 21 institutions from 2011 to 2019. The propensity-score method of inverse-probability of treatment weighting was used to balance the baseline characteristics across surgical approaches. Univariate logistic regression models were applied to test risk factors for conversion. Multivariable logistic regression analysis was conducted using a stepwise model selection method. RESULTS: Seven thousand two hundred sixteen patients undergoing lobectomy were identified: RL (n = 2968), VATS (n = 2831), and open lobectomy (n = 1417). RL had lower conversion rate compared with VATS (3.6% vs 12.9%; P < .0001). In the multivariable regression model, tumor size and neoadjuvant therapy were the most significant risk factors for conversion, followed by prior cardiac surgery, congestive heart failure, chronic obstructive pulmonary disease, VATS approach, male gender, body mass index, and forced expiratory volume in 1 minute. Conversions for anatomical reasons were more common in VATS than RL (66.6% vs 45.6%; P = .0002); however, conversions for vascular reasons were more common in RL than VATS (24.8% vs 14%; P = .01). The rate of emergency conversions was comparable between RL and VATS (0.5% vs 0.7%; P = .25) with no intraoperative mortalities. CONCLUSIONS: Converted minimally invasive lobectomies were not associated with worse perioperative mortality compared with open lobectomy. Compared with VATS lobectomy, RL is associated with a lower probability of conversion in this propensity-score matched cohort study.

Robotic Mediastinal Surgery.

The robotic platform can be viewed as an advanced thoracoscopic instrument and can be utilized for any pathology amenable to thoracoscopic surgery. This ultimately comes down to surgeon comfort, but many have demonstrated the robotic approach to be useful in benign and malignant mediastinal disease in all compartments with at least equivalent-if not superior-outcomes compared to sternotomy for many metrics. There are various robotic approaches to the same compartments (such as with thymectomy), and no one robotic approach has proven superior to another. Here we describe our robotic approach to common mediastinal pathology.

Effects of a single subcutaneous dose of enoxaparin on veterinary viscoelastic coagulation monitor variables in healthy cats: Double blind, placebo controlled cross-over trial.

BACKGROUND: Cats placed on anticoagulant medication require frequent monitoring. The veterinary viscoelastic coagulation monitor (VCM-Vet) could provide a convenient and cost-effective monitoring, enabling therapeutic decision making. HYPOTHESIS/OBJECTIVES: Enoxaparin will lead to changes in VCM-Vet variables and these will correlate with antiXa activity. ANIMALS: Twenty-one healthy cats. METHODS: Cats were randomized to receive either enoxaparin (1 mg/kg) subcutaneously or 0.9% NaCl (equal volume) and crossed over with a 7-day washout period. The investigators were blinded to group allocation until data analysis. Jugular blood samples were drawn at time 0, and 2, 4, and 8 hours after injection for VCM-Vet analysis within 2 min of collection. Citrated plasma was frozen at -80°C for antiXa activity analysis. A Generalized Linear Model was completed to assess changes between baseline measurements and all time points. RESULTS: Significant differences between the enoxaparin-treated cats and controls at for T0h and T2h were found and presented as mean ± SD for clotting time (enoxaparin, 593.4 ± 78.0 s; control, 448.5 ± 50.3 s, P < .001), clot formation time (enoxaparin, 183.1 ± 41.7 s; control, 155.4 ± 28.0 s, P = .001), and alpha angle (enoxaparin, 52.4 ± 6.1°; control, 56.9 ± 3.7 s, P = .003). AntiXa activity was significantly different between T0 and all other timepoints for the enoxaparin group (P < .001). There was no correlation between changes in clotting time and antiXa activity. CONCLUSIONS AND CLINICAL IMPORTANCE: The VCM-Vet detects a difference at 2 hours after single-dose enoxaparin administration and it can be useful for anticoagulant therapy monitoring in cats.

MRI characteristics of canine prostatic neoplasia.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.