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The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas. In this review, we highlight several key factors that have contributed to the ongoing democratization of ultrasound imaging, including portable and handheld devices, recent advancements in technology, and training and education. Examples of diagnostic point-of-care ultrasound (POCUS) imaging used in emergency and critical care, gastroenterology, musculoskeletal applications, and other practices are provided for both human and veterinary medicine. Open challenges and the future of POCUS imaging are presented, including the emerging role of artificial intelligence in technology development.

Objective: Integrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) in vitro and in animal models in vivo . The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs., Design: OA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 10 7 integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carpi were evaluated by computed tomography (CT), MRI, histology, and for macroscopic pathology and integrin α10-MSCs were traced in the joint tissues., Results: Lameness and response to carpal flexion significantly improved over time following integrin α10-MSC treatment. Treated horses had milder macroscopic cartilage pathology and lower cartilage histology scores than the untreated group. Prostaglandin E2 and interleukin-10 increased in the SF after integrin α10-MSC injection. Integrin α10-MSCs were found in SF from treated horses up to day 17 after treatment, and in the articular cartilage and subchondral bone from 5 of 8 treated horses after euthanasia at 52 days after treatment. The integrin α10-MSC injection did not cause joint flare., Conclusion: This study demonstrates that intra-articular (IA) injection of integrin α10-MSCs appears to be safe, alleviate pathological changes in the joint, and improve joint function in an equine post-traumatic osteoarthritis (PTOA) model. The results suggest that integrin α10-MSCs hold promise as a disease-modifying osteoarthritis drug (DMOAD)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.L.-Å. is the CEO and CSO of Xintela AB, holds stock in the company, and is an inventor of a patent related to this study. K.U. was an employee of and holds stock in Xintela AB. L.A.V was an employee of Xintela AB.

Objective: To evaluate whether patients with advanced cancer prefer surgeons to use the best case/worst case (BC/WC) communication framework over the traditional risk/benefit (R/B) framework in the context of palliative surgical scenarios., Background: Identifying the patient's preferred communication frameworks may improve satisfaction and outcome measures during difficult clinical decision-making., Methods: In a video-vignette-based randomized, double-blinded study from November 2020 to May 2021, patients with advanced cancer viewed 2 videos depicting a physician-patient encounter in a palliative surgical scenario, in which the surgeon uses either the BC/WC or the R/B framework to discuss treatment options. The primary outcome was the patients' preferred video surgeon., Results: One hundred fifty-five patients were approached to participate; 66 were randomized and 58 completed the study (mean age 55.8 ± 13.8 years, 60.3% males). 22 patients (37.9%, 95% CI: 25.4%-50.4%) preferred the surgeon using the BC/WC framework, 21 (36.2%, 95% CI: 23.8%-48.6%) preferred the surgeon using the R/B framework, and 15 (25.9%, 95% CI: 14.6%-37.2%) indicated no preference. High trust in the medical profession was inversely associated with a preference for the surgeon using BC/WC framework (odds ratio: 0.83, 95% CI: 0.70-0.98, P = 0.03). The BC/WC framework rated higher for perceived surgeon's listening (4.6 ± 0.7 vs 4.3±0.9, P = 0.03) and confidence in the surgeon's trustworthiness (4.3 ± 0.8 vs 4.0 ± 0.9, P = 0.04)., Conclusions: Surgeon use of the BC/WC communication framework was not universally preferred but was as acceptable to patients as the traditional R/B framework and rated higher in certain aspects of communication. A preference for a surgeon using BC/WC was associated with lower trust in the medical profession. Surgeons should consider the BC/WC framework to individualize their approach to challenging clinical discussions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The "claw sign" is a radiographic sign studied in human imaging to determine if a mass arises from a solid structure or organ versus a close adjacent location, resulting in distortion of the outline of an organ. We investigated its utility in characterizing MRI axial localization of peripherally located intracranial glioma versus meningioma, due to their overlap in MRI appearance. This retrospective, secondary analysis, cross-sectional study aimed to report the sensitivity, specificity, and inter- and intraobserver variabilities using kappa statistics, hypothesizing that the claw sign will have strong inter- and intraobserver agreement (κ > 0.8). Dogs with a histologically confirmed diagnosis of peripherally located glioma or meningioma and available 3T MRI data were retrieved from medical record archives from 2009 to 2021. A total of 27 cases, 11 glioma and 16 meningioma, were included. The postcontrast T1-weighted images were provided to five blinded image evaluators in two separate randomized sessions separated by a 6-week wash out period. Prior to the first evaluation, evaluators were provided with a training video and set of training cases for the "claw sign," which were excluded from the study. Evaluators were asked to rate cases as "positive," "negative," or "indeterminate" for the "claw sign." The sensitivity and specificity for the "claw sign" for the first session were 85.5% and 80%, respectively. The interobserver agreement for identifying the "claw sign" was moderate (κ = 0.48), and the intraobserver agreement across the two sessions was substantial (κ = 0.72). These findings indicate the claw sign is supportive but not pathognomonic for intra-axial localization in cases of canine glioma on MRI., (© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Introduction: Accurate radiographic assessment of bone healing is vital in determining both clinical treatment and for assessing interventions aimed at the promotion of bone healing. Several scoring systems have been used to evaluate osteotomy changes following tibial plateau leveling osteotomy (TPLO). The goal of this study was to compare the ability of five radiographic scoring systems to identify changes in bone healing following TPLO over time (Aim I), and to evaluate the influence of limb positioning on TPLO osteotomy scoring (Aim II)., Materials and Methods: Phase I-A randomized, blinded, prospective study was conducted using similarly positioned postoperative TPLO radiographs from seven dogs taken immediately postoperatively, 6-weeks, and 8-weeks postoperatively. Ten reviewers assessed the radiographs, and five different scoring systems were tested for each set including three previously published ones, a Visual Analog Score (VAS), and a subjective 11-point scale. For each system, responses for 6-week postoperative were compared to 8-week postoperative. Scores were judged as correct (=showing an increase in score), incorrect (=decrease in score), or unchanged (=same score). Phase II-An international group of 39 reviewers was asked to score radiographs from three dogs, taken in different positions, using the VAS grading system. Scores were averaged and comparisons were made for each set., Results: Phase I-The VAS system identified the greatest number of sets correctly (76%), with the least unchanged scores (15%), and 9% incorrect scores. Phase II-All three patients had an increase in the average difference between VAS-scores for differently positioned radiographs compared to similarly positioned radiographs. The magnitude of change between different positions far exceeded the magnitude of comparison of the similarly positioned radiographs from the 6- and 8-week time point., Discussion/conclusion: The VAS system appears to be the most appropriate of the tested systems to identify small changes in bone healing. In addition, the positioning of postoperative TPLO radiographs makes a substantial difference in the healing score that is assigned. Care must be undertaken when performing postoperative radiographs in both the clinical and research setting to ensure accurate assessment of bone healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leal, Lambrechts, Crowley, Griffin, Karnia, Torres, Maritato, Kieves and Duerr.)

Objective: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC)., Background: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication., Methods: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups., Results: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01)., Conclusions: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Malignant gliomas have a highly immune suppressive tumor microenvironment (TME) which renders them largely unresponsive to conventional therapeutics. Therefore, the present study evaluated a therapeutic protocol designed overcome the immune barrier by combining myeloid cell targeted immunotherapy with tumor vaccination., Experimental Design: We utilized a spontaneously occurring canine glioma model to investigate an oral TME modifying immunotherapy in conjunction with cancer stem cell (CSC) vaccination. Dogs were treated daily with losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) plus anti-CSC vaccination on a bi-weekly then monthly schedule. Tumor volume was monitored by MRI and correlated with patient immune responses., Results: Ten dogs with histologically confirmed gliomas were enrolled into a prospective, open-label clinical trial to evaluate the immunotherapy protocol. Partial tumor regression was observed in 2 dogs, while 6 dogs experienced stable disease, for an overall clinical benefit rate of 80%. Overall survival times (median = 351 days) and progression-free intervals (median = 163 days) were comparable to prior studies evaluating surgical debulking followed by immunotherapy. Dogs with detectable anti-CSC antibody responses had an increased overall survival time relative to dogs that did not generate antibody responses (vaccine responder MST = 500 days; vaccine non-responder MST = 218 days; p = 0.02)., Conclusions: These findings suggest that combining myeloid cell targeted oral immunotherapy with tumor vaccination can generate objective tumor responses, even in the absence of conventional therapy. Overall, this approach has promise as a readily implemented therapeutic strategy for use in brain cancer patients., Competing Interests: Declaration of interests. The authors have the following conflicts to disclose: SD is an inventor on an issued patent (US 10,512,687) covering the vaccine adjuvant used in these studies. The other authors declare no potential conflicts of interest.

Diffusion-weighted MRI (DWI) is often used to guide clinical interpretation of intraparenchymal brain lesions when there is suspicion for a cerebrovascular accident (CVA). Despite widespread evidence that imaging and patient parameters can influence diffusion-weighted measurements, such as apparent diffusion coefficient (ADC), there is little published data on such measurements for naturally occurring CVA in clinical cases in dogs. We describe a series of 22 presumed and confirmed spontaneous canine CVA with known time of clinical onset imaged on a single 3T magnet between 2011 and 2021. Median ADC values of < 1.0x10 -3 mm 2 /s were seen in normal control tissues as well as within CVAs. Absolute and relative ADC values in CVAs were well-correlated (R 2 = 0.82). Absolute ADC values < 1.0x10 -3 mm 2 /s prevailed within ischemic CVAs, though there were exceptions, including some lesions of < 5 days age. Some lesions showed reduced absolute but not relative ADC values when compared to matched normal contralateral tissue. CVAs with large hemorrhagic components did not show restricted diffusion. Variation in the DWI sequence used impacted the ADC values obtained. Failure to identify a region of ADC < 1.0x10 -3 mm 2 /s should not exclude CVA from the differential list when clinical suspicion is high., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Boudreau, Kerwin, DuPont, Levine and Griffin.)

Magnetic resonance imaging (MRI) is commonly used to evaluate the central nervous system (CNS) in dogs; however, published studies describing the MRI appearance of cranial and vertebral osteosarcoma are scarce. In this multicenter, retrospective, case series study, MRI studies of 35 dogs with cranial or vertebral osteosarcoma were prospectively scored by consensus of two veterinary radiologists. Recorded characteristics were location, signal intensity (compared to gray matter), homogeneity, contrast enhancement, margin delineation, local invasion, osteolysis, osteosclerosis, zone of transition, periosteal proliferation, pathological fracture, meningeal/CNS involvement, and presence of metastatic disease. Locations included the parietal bone (n = 1), occipital bone (n = 2), or cervical (n = 5), thoracic (n = 17), lumbar (n = 7), or sacral vertebrae (n = 3). Common features included signal heterogeneity in T2-weighted (T2W) images (n = 35), contrast enhancement (in all 34 dogs with postcontrast MRI), osteolysis (n = 34), compression of the CNS or cauda equina (n = 33), an associated soft tissue mass (n = 33), a long zone of transition (n = 30), osteosclerosis (n = 28), signal isointensity to normal-appearing gray matter in T1-weighted images (T1W, n = 26), and T2W hyperintensity of adjacent brain or spinal cord (n = 23). Other findings included periosteal proliferation (n = 18), meningeal contrast enhancement (n = 17), T1W and T2W hypointense foci in the soft tissue mass (n = 14), invasion into adjacent bones (n = 10), pathological vertebral fractures (n = 7), regional lymphadenopathy (n = 6), skip metastases (n = 2), lung nodule (n = 1), diaphragmatic nodule (n = 1), and brain invasion (n = 1). Contrast enhancement was typically strong and heterogeneous. Magnetic resonance imaging features of cranial and vertebral osteosarcoma were analogous to those previously reported for other imaging modalities. Osteosarcoma should be a differential diagnosis for compressive, contrast-enhancing, osteolytic lesions of the cranium or vertebrae., (© 2022 American College of Veterinary Radiology.)

Articular cartilage thinning is an important hallmark of osteoarthritis (OA), and ultrasonography (US) is a clinically accessible tool potentially suitable for repeated evaluation. The aim of the present prospective methods comparison study was to validate US as a tool for measuring cartilage thickness in the carpus of the horse. Eight Standardbred trotters underwent US examination with 9 and 15 MHz linear transducers. Six anatomical locations in the radiocarpal joint (RCJ) and middle carpal joint (MCJ) were examined. The same joints were assessed by ultrahigh field (9.4 Tesla) magnetic resonance imaging (MRI) and histology. Associations between measurements obtained by the different modalities were assessed by ANOVA, Deming regression, Pearson correlation and Bland-Altman plots. Histologically assessed total cartilage thickness (the noncalcified cartilage (NCC) plus the calcified cartilage zone (CCZ)) overestimated thickness compared to MRI (P < 0.01) and US (P < 0.01). US 15 MHz had substantial agreement with MRI and NCC histology, and repeatability was acceptable (coefficient of variation = 8.6-17.9%) when used for assessment of cartilage thickness in the RCJ. In contrast, 9 MHz US showed poorer agreement with MRI and NCC histology, as it overestimated the thickness of thin cartilage and underestimated the thickness of thicker cartilage in the RCJ and MCJ. Moreover, repeatability was suboptimal (coefficient of variation = 10.4-26.3%). A 15 MHz transducer US is recommended for detecting changes in RCJ cartilage thickness or monitoring development over time, and it has the potential for noninvasive assessment of cartilage health in horses., (© 2022 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Objective: This study aimed to identify risk factors for recurrence after pancreatic resection for intraductal papillary mucinous neoplasm (IPMN)., Summary Background Data: Long-term follow-up data on recurrence after surgical resection for IPMN are currently lacking. Previous studies have presented mixed results on the role of margin status in risk of recurrence after surgical resection., Methods: A total of 126 patients that underwent resection for noninvasive IPMN were followed for a median of 9.5 years. Dedicated pathological and radiological reviews were performed to correlate clinical and pathological features (including detailed pathological features of the parenchymal margin) with recurrence after surgical resection. In addition, in a subset of 32 patients with positive margins, we determined the relationship between the margin and original IPMN using driver gene mutations identified by next-generation sequencing., Results: Family history of pancreatic cancer and high-grade IPMN was identified as risk factors for recurrence in both uni- and multivariate analysis (adjusted hazard ratio 3.05 and 1.88, respectively). Although positive margin was not significantly associated with recurrence in our cohort, the size and grade of the dysplastic focus at the margin were significantly correlated with recurrence in margin-positive patients. Genetic analyses showed that the neoplastic epithelium at the margin was independent from the original IPMN in at least 9 of 32 cases (28%). The majority of recurrences (74%) occurred after 3 years, and a significant minority (32%) occurred after 5 years., Conclusion: Sustained postoperative surveillance for all patients is indicated, particularly those with risk factors such has family history and high-grade dysplasia., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Main-duct (MD) intraductal papillary mucinous neoplasm (IPMN) is associated with malignancy risk. There is a lack of consensus on treatment (partial or total pancreatectomy) when the MD is diffusely involved. We sought to characterize the pancreatic remnant fate after partial pancreatectomy for non-invasive diffuse MD-IPMN., Methods: Consecutive patients with partial pancreatectomy for non-invasive MD-IPMN from 2004 to 2016 were analyzed. Diffuse MD-IPMN was defined by preoperative imaging as dilation of the MD in the head of the pancreas more than 5 mm and involving the whole gland., Results: Of 127 patients with resected non-invasive MD-IPMN, 47 (37%) had diffuse MD involvement. Eleven of 47(23%) patients developed imaging evidence of progression or new cystic disease in the pancreatic remnant. Patients with diffuse MD-IPMN were older (73yrs vs 67yrs, p = 0.009), more likely to receive a pancreaticoduodenectomy (96% vs 56%, p < 0.001) and have high-grade dysplasia (51% vs 31%, p = 0.025) than those with focal MD involvement. Diffuse MD involvement was not associated with shorter PFS following partial pancreatectomy (p = 0.613)., Conclusion: Partial pancreatectomy is an appropriate surgical approach for diffuse MD-IPMN, and is not associated with earlier progression after surgery as compared to partial pancreatectomy for focal dilation., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Intracranial extra-axial histiocytic sarcoma shares common MRI features with meningioma. As histiocytic sarcoma carries a generally worse prognosis than meningioma, the ability to differentiate between these two neoplasms is of clinical value. The aim of this retrospective diagnostic accuracy and observer agreement study was to evaluate the accuracy and reliability of high-field MRI to differentiate between these two tumors, using standard pulse sequences and published MRI features. A total of 51 dogs were included (26 meningiomas and 25 histiocytic sarcomas). Magnetic resonance imaging examinations were independently assessed by three experienced board-certified radiologists, evaluating 18 imaging features. They were asked to assign each case to one of three categories (meningioma, histiocytic sarcoma, and undetermined). Agreement for the MRI diagnosis across all three reviewers was moderate (κ 0.54) while paired interobserver agreement ranged from moderate to substantial (κ 0.58-0.74) with percent agreement ranging between 86.1% and 87.7%. Overall, the probability of correctly diagnosing meningioma in a dog with this tumor ranged between 79.2% and 94.4%, and the probability of correctly diagnosing histiocytic sarcoma in a dog with this tumor ranged between 76.0% and 92.3%. The overall probability to diagnose the correct tumor, irrespective of type, ranged between 79.2% and 89.7%. Histiocytic sarcomas tended to have more extensive edema and more often had combined perilesional and distant meningeal enhancement affecting both pachy- and leptomeninges, while for meningiomas, meningeal enhancement tended to more commonly be perilesional and pachymeningeal. Imaging features that seemed more useful to make a correct diagnosis included "location/type of meningeal enhancement," "osseous changes in the adjacent neurocranium," "cystic changes," and "herniation severity.", (© 2021 American College of Veterinary Radiology.)

Background: Magnetic resonance imaging is the method of choice for diagnosing spinal cord neoplasia, but the accuracy of designating the relationship of a neoplasm to the meninges and agreement among observers is unknown., Objectives: To determine agreement among observers and accuracy of diagnosis compared with histology when diagnosing lesion location based on relationship to the meninges., Animals: Magnetic resonance images from 53 dogs with intradural extramedullary and intramedullary spinal neoplasms and 17 dogs with degenerative myelopathy., Methods: Six observers were supplied with 2 sets of 35 images at different time points and asked to designate lesion location. Agreement in each set was analyzed using kappa (κ) statistics. We tabulated total correct allocations and calculated sensitivity, specificity, and likelihood ratios for location designation from images compared with known histologic location for lesions confined to 1 location only., Results: Agreement in the first set of images was moderate (κ = 0.51; 95% confidence interval [CI], 0.43-0.58) and in the second, substantial (κ = 0.69; 95% CI, 0.66-0.79). In the accuracy study, 180 (75%) of the 240 diagnostic calls were correct. Sensitivity and specificity were moderate to high for all compartments, except poor sensitivity was found for intradural extramedullary lesions. Positive likelihood ratios were high for intradural extramedullary lesions and degenerative myelopathy., Conclusions and Clinical Importance: Overall accuracy in diagnosis was reasonable, and positive diagnostic calls for intradural extramedullary lesions and negative calls for intramedullary lesions are likely to be helpful. Observers exhibited considerable disagreement in designation of lesions relationship to the meninges., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Awareness of exocrine pancreatic insufficiency (EPI) in cats has increased since the development of an assay for feline trypsin-like immunoreactivity (fTLI). Ultrasound findings in cats with EPI have only been reported rarely and described as nonspecific., Hypothesis/objectives: To describe the ultrasonographic findings, clinical signs, and concurrent diseases in cats with EPI., Animals: Twenty-two client-owned cats with EPI., Methods: Multicenter retrospective descriptive study including cats with serum fTLI concentration ≤8 μg/L and an abdominal ultrasound examination performed within 6 weeks of fTLI measurement. Sonographic measurements of maximal pancreatic thickness and maximal pancreatic duct diameter as well as ratios of pancreatic duct diameter to pancreatic thickness were obtained. Additional sonographic findings, concurrent conditions, and clinical signs were recorded., Results: The most common clinical sign was weight loss (15/22 cats). Chronic enteropathy was the most common concurrent disease (13/22 cats). In 39% of cats, the pancreas had minimal or no sonographic alterations. Pancreatic duct dilatation (>2.5 mm), pancreatic duct tortuosity with variable diameter, or both were seen in 6/13 cats. The pancreatic parenchyma was subjectively thin in 6 cats. A significant relationship was found between subjectively thin pancreatic parenchyma and increased pancreatic duct size : pancreatic thickness ratio (P = .004). Diffuse gastrointestinal dilatation with echogenic content was observed in 8/22 cats., Conclusion: Exocrine pancreatic insufficiency often causes minimal to no sonographic pancreatic changes. Nonetheless, the findings of thin pancreatic parenchyma, pancreatic duct dilatation, or diffuse small intestinal dilatation with echogenic contents in cats with unexplained weight loss or unformed feces should raise clinical suspicion for EPI., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

There is a great demand for accurate non-invasive measures to better define the natural history of disease progression or treatment outcome in Duchenne muscular dystrophy (DMD) and to facilitate the inclusion of a large range of participants in DMD clinical trials. This review aims to investigate which MRI sequences and analysis methods have been used and to identify future needs. Medline, Embase, Scopus, Web of Science, Inspec, and Compendex databases were searched up to 2 November 2019, using keywords "magnetic resonance imaging" and "Duchenne muscular dystrophy." The review showed the trend of using T1w and T2w MRI images for semi-qualitative inspection of structural alterations of DMD muscle using a diversity of grading scales, with increasing use of T2map, Dixon, and MR spectroscopy (MRS). High-field (>3T) MRI dominated the studies with animal models. The quantitative MRI techniques have allowed a more precise estimation of local or generalized disease severity. Longitudinal studies assessing the effect of an intervention have also become more prominent, in both clinical and animal model subjects. Quality assessment of the included longitudinal studies was performed using the Newcastle-Ottawa Quality Assessment Scale adapted to comprise bias in selection, comparability, exposure, and outcome. Additional large clinical trials are needed to consolidate research using MRI as a biomarker in DMD and to validate findings against established gold standards. This future work should use a multiparametric and quantitative MRI acquisition protocol, assess the repeatability of measurements, and correlate findings to histologic parameters., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Computed tomography (CT) is the imaging modality of choice to evaluate patients with acute head trauma. However, magnetic resonance imaging (MRI) may be chosen in select cases. The objectives of this study were to evaluate the agreement of MRI with CT in the assessment for presence or absence of acute skull fractures in a canine and feline cadaver model, compare seven different MRI sequences (T1-W, T2-W, T2-FLAIR, PD-W, T2 * -W, "SPACE" and "VIBE"), and determine agreement of four different MRI readers with CT data. Pre- and post-trauma CT and MRI studies were performed on 10 canine and 10 feline cadaver heads. Agreement of MRI with CT as to presence or absence of a fracture was determined for 26 individual osseous structures and four anatomic regions (cranium, face, skull base, temporomandibular joint). Overall, there was 93.5% agreement in assessing a fracture as present or absent between MRI and CT, with a significant difference between the pre and post trauma studies (99.4 vs. 87.6%; p < 0.0001; OR 0.042; 95% CI 0.034-0.052). There was no significant difference between dogs and cats. The agreement for the different MRI sequences with CT ranged from 92.6% (T2 * -W) to 94.4% (PD-W). There was higher agreement of MRI with CT in the evaluation for fractures of the face than other anatomic regions. Agreement with CT for individual MRI readers ranged from 92.6 to 94.7%. A PD-W sequence should be added to the MR protocol when evaluating the small animal head trauma patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hecht, Anderson, Castel, Griffin, Hespel, Nelson and Sun.)

Early prognostic information in cases of severe spinal cord injury can aid treatment planning and stratification for clinical trials. Analysis of intraparenchymal signal change on magnetic resonance imaging has been suggested to inform outcome prediction in traumatic spinal cord injury. We hypothesized that intraparenchymal T 2 -weighted hypointensity would be associated with a lower potential for functional recovery and a higher risk of progressive neurological deterioration in dogs with acute, severe, naturally occurring spinal cord injury. Our objectives were to: 1) demonstrate capacity for machine-learning criteria to identify clinically relevant regions of hypointensity and 2) compare clinical outcomes for cases with and without such regions. A total of 95 dogs with complete spinal cord injury were evaluated. An image classification system, based on Speeded-Up Robust Features (SURF), was trained to recognize individual axial T 2 -weighted slices that contained hypointensity. The presence of such slices in a given transverse series was correlated with a lower chance of functional recovery (odds ratio [OR], 0.08; confidence interval [CI], 0.02-0.38; p  < 10 -3 ) and with a higher risk of neurological deterioration (OR, 0.14; 95% CI, 0.05-0.42; p  < 10 -3 ). Identification of intraparenchymal T 2 -weighted hypointensity in severe, naturally occurring spinal cord injury may be assisted by an image classification tool and is correlated with functional recovery.

Background: Noninvasive ventilation (NIV) is commonly used to support children with respiratory failure, but detailed patterns of real-world use are lacking. The aim of our study was to describe use patterns of NIV via electronic medical record (EMR) data., Methods: We performed a retrospective electronic chart review in a tertiary care pediatric ICU in the United States. Subjects admitted to the pediatric ICU from 2014 to 2017 who were mechanically ventilated were included in the study., Results: The median number of discrete device episodes, defined as a time on support without interruption, was 20 (interquartile range [IQR] 8-49) per subject. The median duration of bi-level positive airway pressure (BPAP) support prior to interruption was 6.3 h (IQR 2.4-10.4); the median duration of CPAP was 6 h (IQR 2.1-10.4). Interruptions to BPAP had a median duration of 6.3 h (IQR 2-15.5); interruptions to CPAP had a median duration of 8.6 h (IQR 2.2-16.8). Use of NIV followed a diurnal pattern, with 44% of BPAP and 42% of CPAP subjects initiating support between 7:00 pm and midnight, and 49% of BPAP and 46% of CPAP subjects stopping support between 5:00 am and 10:00 am., Conclusions: NIV was frequently interrupted, and initiation and discontinuation of NIV follows a diurnal pattern. Use of EMR data collected for routine clinical care allowed the analysis of granular details of typical use patterns. Understanding NIV use patterns may be particularly important to understanding the burden of pediatric ICU bed utilization for nocturnal NIV. To our knowledge, this is the first study to examine in detail the use of pediatric NIV and to define diurnal use and frequent interruptions to support., (Copyright © 2020 by Daedalus Enterprises.)

Introduction: Golden retriever muscular dystrophy (GRMD) is a spontaneous X-linked canine model of Duchenne muscular dystrophy that resembles the human condition. Muscle percentage index (MPI) is proposed as an imaging biomarker of disease severity in GRMD., Methods: To assess MPI, we used MRI data acquired from nine GRMD samples using a 4.7 T small-bore scanner. A machine learning approach was used with eight raw quantitative mapping of MRI data images (T1m, T2m, two Dixon maps, and four diffusion tensor imaging maps), three types of texture descriptors (local binary pattern, gray-level co-occurrence matrix, gray-level run-length matrix), and a gradient descriptor (histogram of oriented gradients)., Results: The confusion matrix, averaged over all samples, showed 93.5% of muscle pixels classified correctly. The classification, optimized in a leave-one-out cross-validation, provided an average accuracy of 80% with a discrepancy in overestimation for young (8%) and old (20%) dogs., Discussion: MPI could be useful for quantifying GRMD severity, but careful interpretation is needed for severe cases., (© 2019 Wiley Periodicals, Inc.)

Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis., Methods: We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations., Results: We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis., Conclusions: In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: We assessed the growth, distribution, and characteristics of pediatric intensive care in 2016., Design: Hospitals with PICUs were identified from prior surveys, databases, online searching, and clinician networking. A structured web-based survey was distributed in 2016 and compared with responses in a 2001 survey., Setting: PICUs were defined as a separate unit, specifically for the treatment of children with life-threatening conditions. PICU hospitals contained greater than or equal to 1 PICU., Subjects: Physician medical directors and nurse managers., Interventions: None., Measurements and Main Results: PICU beds per pediatric population (< 18 yr), PICU bed distribution by state and region, and PICU characteristics and their relationship with PICU beds were measured. Between 2001 and 2016, the U.S. pediatric population grew 1.9% to greater than 73.6 million children, and PICU hospitals decreased 0.9% from 347 to 344 (58 closed, 55 opened). In contrast, PICU bed numbers increased 43% (4,135 to 5,908 beds); the median PICU beds per PICU hospital rose from 9 to 12 (interquartile range 8, 20 beds). PICU hospitals with greater than or equal to 15 beds in 2001 had significant bed growth by 2016, whereas PICU hospitals with less than 15 beds experienced little average growth. In 2016, there were eight PICU beds per 100,000 U.S. children (5.7 in 2001), with U.S. census region differences in bed availability (6.8 to 8.8 beds/100,000 children). Sixty-three PICU hospitals (18%) accounted for 47% of PICU beds. Specialized PICUs were available in 59 hospitals (17.2%), 48 were cardiac (129% growth). Academic affiliation, extracorporeal membrane oxygenation availability, and 24-hour in-hospital intensivist staffing increased with PICU beds per hospital., Conclusions: U.S. PICU bed growth exceeded pediatric population growth over 15 years with a relatively small percentage of PICU hospitals containing almost half of all PICU beds. PICU bed availability is variable across U.S. states and regions, potentially influencing access to care and emergency preparedness.

Objectives: To estimate the sensitivity and specificity of ultrasound and CT for localising solitary hepatic masses to particular liver divisions., Materials and Methods: Dogs diagnosed with a solitary liver mass by ultrasound and/or CT, with surgical or necropsy confirmation within 1 month of imaging. Ultrasound reports were reviewed for mass location. CT scans were reviewed by two radiologists and mass location was determined by consensus agreement. Sensitivity and specificity were calculated for ultrasound and CT for each liver division., Results: Fourteen of 71 dogs had CT only, 27 of 71 had ultrasound only and 30 of 71 had both. Location was correctly predicted in 42 of 57 dogs (74%) by ultrasound and in 37 of 44 dogs (84%) by CT. Both CT and ultrasound had high specificity for localising masses in all divisions. Sensitivity varied among divisions and was highest for left division masses., Clinical Significance: The results suggest that either imaging modality is appropriate for presurgical planning. Prospective studies are recommended to help identify additional factors that may aid in determination of hepatic mass location., (© 2019 British Small Animal Veterinary Association.)

Introduction: Golden retriever muscular dystrophy (GRMD), an X-linked recessive disorder, causes similar phenotypic features to Duchenne muscular dystrophy (DMD). There is currently a need for a quantitative and reproducible monitoring of disease progression for GRMD and DMD., Methods: To assess severity in the GRMD, we analyzed texture features extracted from multi-parametric MRI (T1w, T2w, T1m, T2m, and Dixon images) using 5 feature extraction methods and classified using support vector machines., Results: A single feature from qualitative images can provide 89% maximal accuracy. Furthermore, 2 features from T1w, T2m, or Dixon images provided highest accuracy. When considering a tradeoff between scan-time and computational complexity, T2m images provided good accuracy at a lower acquisition and processing time and effort., Conclusions: The combination of MRI texture features improved the classification accuracy for assessment of disease progression in GRMD with evaluation of the heterogenous nature of skeletal muscles as reflection of the histopathological changes. Muscle Nerve 59:380-386, 2019., (© 2018 Wiley Periodicals, Inc.)

Limited information is available on the ultrasonographic characteristics of extruded gallbladder mucoceles. The objective of this retrospective case series study was to describe the ultrasonographic features of extruded gallbladder mucoceles in a group of dogs. Medical records of four veterinary centers were searched between June 2010 and January 2018 for all dogs with a suspected extruded gallbladder mucocele based on abdominal ultrasound. Seven client-owned dogs met the inclusion criteria. All seven dogs had a discrete, heteroechoic, multilayered, stellate, or striated mass within the peritoneal cavity. Blood flow was not present in these structures. Four of these structures were identified in the caudal abdomen. In five cases, the gallbladder lumen was filled with material similar in appearance to the free-floating peritoneal mass. Four cases were confirmed surgically and one case was confirmed at necropsy. Histopathology of the gallbladder wall was evaluated in all surgical cases and analysis of the free-floating material was performed in one of the four cases. Extruded gallbladder mucoceles have common imaging characteristics that may be helpful in establishing a presumptive diagnosis. Additionally, these structures may have extensive migratory capacity. The results of the study justify the recommendation for exploration of the entire abdomen during cholecystectomy for gallbladder mucocele removal., (© 2018 American College of Veterinary Radiology.)

A 7-year-old castrated male Maltese dog was presented for increased respiratory sounds, inability to bark, dysphagia, and hyporexia. Radiographs revealed an ovoid, opaque mass in the caudal nasopharynx. An airway examination and computed tomography scan were followed by endoscopic polypoidectomy. The mass was a hemangiosarcoma, and the patient survived > 13 months.

The National Cancer Institute Comparative Brain Tumor Consortium, Patient Outcomes Working Group, propose a consensus document in support of standardized magnetic resonance imaging protocols for canine brain tumor clinical trials. The intent of this manuscript is to address the widely acknowledged need to ensure canine brain tumor imaging protocols are relevant and have sufficient equivalency to translate to human studies such that: (1) multi-institutional studies can be performed with minimal inter-institutional variation, and (2) imaging protocols are consistent with human consensus recommendations to permit reliable translation of imaging data to human clinical trials. Consensus recommendations include pre- and postcontrast three-dimensional T1-weighted images, T2-weighted turbo spin echo in all three planes, T2*-weighted gradient recalled echo, T2-weighted fluid attenuated inversion recovery, and diffusion weighted imaging/diffusion tensor imaging in transverse plane; field of view of ≤150 mm; slice thickness of ≤2 mm, matrix ≥ 256 for two-dimensional images, and 150 or 256 for three-dimensional images., (© 2018 American College of Veterinary Radiology.)

Background: Sarcomatoid carcinoma of the pancreas (SCP) is a rare histologic subtype of undifferentiated pancreatic carcinoma. Historically, this has been associated with a worse overall prognosis than adenocarcinoma. However, the clinical course and surgical outcomes of SCP remain poorly characterized owing to its rarity., Methods: A single-institution, prospectively maintained database was queried for patients who underwent pancreatic resection with a final diagnosis of SCP. We describe their histology, clinicopathologic features, and perioperative outcomes. Survival data are highlighted, and common traits of long-term survivors are examined., Results: Over a 25-year period, 7009 patents underwent pancreatic resection at our institution. Eight (0.11%) were diagnosed with SCP on final histopathology. R0 resection was achieved in six patients (75%). Four patients had early recurrence leading to death (<3 months). Two (25%) experienced long-term survival (>5 years), with the longest surviving nearly 16 years despite the presence of lymph node metastasis. There were no deaths attributed to perioperative complications. Both long-term survivors had disease in the body/tail of the pancreas and received adjuvant radiotherapy. One also received adjuvant gemcitabine-based chemotherapy., Conclusions: SCP is a rarely appreciated subset of pancreatic malignancy that does not necessarily portend to a uniformly dismal prognosis. Although some have rapid recurrence and an early demise, long-term survival may be possible. Future studies are needed to better define the cohort with potential for long-term survival so that aggressive therapies may be tailored appropriately in this patient subset., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is often accompanied by reduced bladder compliance, which contributes to adverse conditions including urinary tract infections and vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive remodeling of the bladder wall, including the extracellular matrix (ECM). Here, we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known for their ability to remodel the ECM, improves bladder compliance in dogs with SCI. We first evaluated dogs with naturally occurring SCIs resulting from intervertebral disc herniation (IVDH). After characterizing the natural history of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs (n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad-spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary outcomes were bladder compliance, as measured by cystometry, and an ordinal gait score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93) were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There were transient, but significantly (p = 0.023) greater, adverse events (31 of 42; 74%) in the GM6001-treated group relative to vehicle controls (22 of 46; 48%). Whereas there were no differences in TSCIS between treatment groups at day 42 (p = 0.9679), bladder compliance was significantly higher in dogs treated with GM6001+DMSO compared to controls (p = 0.0272). Further studies are needed to determine whether this inhibition results from a direct interaction with the bladder wall or indirectly through neural-based mechanisms.

Objective: To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN)., Background: NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer., Methods: We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram., Results: NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma., Conclusions: NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting.

Magnetic resonance imaging (MRI) is a common test for dogs with suspected intradural spinal cord lesions, however studies on diagnostic performance for this test are lacking. Objectives of this multi-institutional, retrospective, case-control study were to estimate sensitivity and specificity of MRI for (1) distinguishing between histopathologically confirmed intradural spinal cord disease versus degenerative myelopathy in dogs, (2) categorizing intradural spinal cord diseases as neoplastic, inflammatory, or vascular; and (3) determining tumor type within the etiologic category of neoplasia. Additional aims were to (1) determine whether knowledge of clinical data affects sensitivity and specificity of MRI diagnoses; and (2) report interrater agreement for MRI classification of intradural spinal lesions. Cases were recruited from participating hospital databases over a 7-year period. Three reviewers independently evaluated each MRI study prior to and after provision of clinical information. A total of 87 cases were sampled (17 degenerative myelopathy, 53 neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions but specificity varied before and after provision of clinical data (68.6% vs. 82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower for classifying inflammatory lesions but improved with provision of clinical data (48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for diagnosing vascular lesions (25.0%). Interrater agreement was very good for correctly diagnosing dogs with intradural lesions (ĸ = 0.882-0.833), and good (ĸ = 0.726-0.671) for diagnosing dogs with neoplasia., (© 2017 American College of Veterinary Radiology.)

Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by dystrophin protein deficiency. Muscle biopsy is the gold standard to determine the disease severity and progression. MRI has shown potential for monitoring disease progression or assessing the treatment effectiveness. In this study, multiple quantitative MRI parameters were used to classify the tissue components in a canine model of DMD disease using histoimmunochemistry analysis as a "ground truth". Results show that multiple MRI parameters may be used to reliably classify the muscular tissue and generate a high-resolution tissue type maps, which can be used as potential non-invasive imaging biomarkers for the DMD.

Background: Cerebral microbleeds (CMBs) are focal intraparenchymal signal voids on gradient-echo magnetic resonance imaging (MRI), corresponding to regions of chronic hemorrhage. In humans, they are associated with systemic disease and shorter survival times. Although similar findings have been identified in dogs, their epidemiology and clinical correlations have not been investigated., Objective: To determine epidemiological features, clinical associations, and associations with outcome for putative CMB-like foci (putative microbleeds [pMBs]) identified by T2*-weighted MRI in dogs., Animals: Five hundred and eighty-two dogs undergoing 3T brain MRI between 2011 and 2016., Methods: Retrospective case-control study. Demographic, diagnostic, and clinicopathological data were obtained from medical records and phone follow-up. Demographic variables were compared between dogs with and without evidence of pMBs. For dogs with such evidence, and a subset of matched controls, associations with clinical presentation, concurrent disease, and survival times were evaluated., Results: Dogs with pMBs were older (P < .001) and smaller (P = .004) than unaffected dogs. Compared to matched controls, they presented more frequently for vestibular signs (P = .030). Cortical atrophy occurred concurrently with pMBs in 26% (14/54) of dogs. Diagnosed renal disease was not significantly associated with pMBs, but proteinuria was more common in dogs with pMBs than in matched controls (odds ratio = 3.01, P = .005). Dogs with pMBs had a shorter median survival time than did matched controls (P = .011)., Conclusions and Clinical Importance: Putative microbleeds occurred in 54 of 582 (9.3%) of dogs undergoing brain MRI, but may not be a normal consequence of aging. They were associated with shorter survival time and proteinuria in the study population., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS)., Background: Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm., Methods: Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression., Results: We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas., Conclusions: Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas.

Background/objectives: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date., Methods: We compared 142 MCNs and 746 IPMNs resected at a single institution. MCNs were reviewed for confirmation of ovarian-type stroma and reclassified according to current WHO guidelines., Results: MCNs presented almost exclusively in middle-aged women (median 47.5 years, 96.5% female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas (92.1%). IPMNs were distributed equally by sex in an older population (median 69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1% vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs (9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs. Patients with an MCN-associated invasive carcinoma had a much better prognosis than did patients with an IPMN-associated invasive carcinoma with 10-year disease-specific survival of 79.6% versus 27.2%, respectively., Conclusion: MCNs have a stereotypical clinical profile that is readily distinguishable from IPMNs based on demographic features, imaging, and pathology. Most MCNs are noninvasive and curable with surgical resection. Prognosis remains excellent even for invasive disease with 10-year survival approaching 80% following resection., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

High-grade pancreatic intraepithelial neoplasia (HG-PanIN) is the major precursor of pancreatic ductal adenocarcinoma (PDAC) and is an ideal target for early detection. To characterize pure HG-PanIN, we analysed 23 isolated HG-PanIN lesions occurring in the absence of PDAC. Whole-exome sequencing of five of these HG-PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. Targeted next-generation sequencing of 17 HG-PanIN lesions identified KRAS mutations in 94% of the lesions. CDKN2A alterations occurred in six HG-PanIN lesions, and RNF43 alterations in five. Mutations in TP53, GNAS, ARID1A, PIK3CA, and TGFBR2 were limited to one or two HG-PanINs. No non-synonymous mutations in SMAD4 were detected. Immunohistochemistry for p53 and SMAD4 proteins in 18 HG-PanINs confirmed the paucity of alterations in these genes, with aberrant p53 labelling noted only in three lesions, two of which were found to be wild type in sequencing analyses. Sixteen adjacent LG-PanIN lesions from ten patients were also sequenced using targeted sequencing. LG-PanIN harboured KRAS mutations in 94% of the lesions; mutations in CDKN2A, TP53, and SMAD4 were not identified. These results suggest that inactivation of TP53 and SMAD4 are late genetic alterations, predominantly occurring in invasive PDAC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Computed tomography (CT) continues to become more widely available for assessment of tumors in dogs, yet there are no studies describing the CT appearance of canine liposarcomas. In this retrospective, multicenter study, CT images of dogs with histologically confirmed liposarcomas were reviewed for size, location, attenuation, contrast enhancement, border definition, internal homogeneity, local infiltration, and mineralization. A total of 24 dogs with 26 liposarcomas were sampled. Mean attenuation was +15.2 (SD = 22.3) Hounsfield units (HU) with a range of -36 to +47.5 HU based on representative regions of interest. Twenty tumors (77%) contained focal areas of fat attenuation. All masses enhanced with contrast medium administration, which is distinct from what has been reported previously in infiltrative lipomas. Other CT features associated with canine liposarcomas included heterogeneous internal attenuation (81%) and lack of a clearly defined capsule (38%) suggesting infiltration of local structures. Six tumors (23%) had foci of mineralization. Findings from the current study indicated that liposarcoma should be considered as a differential diagnosis for mixed-attenuation, contrast-enhancing masses in dogs that contain at least one focus of fat attenuation on precontrast images; however, presence of foci of fat attenuation was not a necessary finding for the diagnosis of canine liposarcoma., (© 2016 American College of Veterinary Radiology.)

Objective: We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC)., Background: PDAC is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification., Methods: Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45., Results: Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02)., Conclusions: CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers., Competing Interests: The author reports no conflicts of interest.

Noninvasive identification of canine articular cartilage injuries is challenging. The objective of this prospective, cadaveric, diagnostic accuracy study was to determine if small field-of-view, three tesla magnetic resonance imaging (MRI) was an accurate method for identifying experimentally induced cartilage defects in canine stifle joints. Forty-two canine cadaveric stifles (n = 6/group) were treated with sham control, 0.5, 1.0, or 3.0 mm deep defects in the medial or lateral femoral condyle. Proton density-weighted, T1-weighted, fast-low angle shot, and T2 maps were generated in dorsal and sagittal planes. Defect location and size were independently determined by two evaluators and compared to histologic measurements. Accuracy of MRI was determined using concordance correlation coefficients. Defects were identified correctly in 98.8% (Evaluator 1) and 98.2% (Evaluator 2) of joints. Concordance correlation coefficients between MRI and histopathology were greater for defect depth (Evaluator 1: 0.68-0.84; Evaluator 2: 0.76-0.83) compared to width (Evaluator 1: 0.30-0.54; Evaluator 2: 0.48-0.68). However, MRI overestimated defect depth (histopathology: 1.65 ± 0.94 mm; Evaluator 1, range of means: 2.07-2.38 mm; Evaluator 2, range of means: 2-2.2 mm) and width (histopathology: 6.98 ± 1.32 mm; Evaluator 1, range of means: 8.33-8.8 mm; Evaluator 2, range of means: 6.64-7.16 mm). Using the paired t-test, the mean T2 relaxation time of cartilage defects was significantly greater than the mean T2 relaxation time of adjacent normal cartilage for both evaluators (P < 0.0001). Findings indicated that MRI is an accurate method for identifying cartilage defects in the cadaveric canine stifle. Additional studies are needed to determine the in vivo accuracy of this method., (© 2016 American College of Veterinary Radiology.)

Background: Prospective studies have identified obstructive sleep apnea (OSA) as a risk factor for increased overall cancer incidence and mortality. The potential role of OSA in the risk or progression of specific cancers is not well known. We hypothesized that pathological differences in pancreatic cancers from OSA cases compared to non-OSA cases would implicate OSA in pancreatic cancer progression., Methods: We reviewed the medical records of 1031 patients who underwent surgical resection without neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2003 and 2014 and compared the TNM classification of their cancer and their overall survival by patient OSA status., Results: OSA cases were significantly more likely than non-OSA cases to have lymph node-negative tumors (37.7% vs. 21.8%, p = 0.004). Differences in the prevalence of nodal involvement of OSA vs. non-OSA cases were not associated with differences in other pathological characteristics such as tumor size, tumor location, resection margin status, vascular or perineural invasion, or other comorbidities more common to OSA cases (BMI, smoking, diabetes). A logistic regression model found that a diagnosis of OSA was an independent predictor of lymph node status (hazard ratio, 0.051, p = 0.038). Patients with OSA had similar overall survival compared to those without OSA (HR, 0.89, (0.65-1.24), p = 0.41)., Conclusion: The observed pathological differences between OSA-associated and non-OSA-associated pancreatic cancers supports the hypothesis that OSA can influence the pathologic features of pancreatic ductal adenocarcinoma., Competing Interests: The authors have declared that no competing interests exist.