Relationship between syringomyelia and myxomatous mitral valve disease in Cavalier King Charles spaniels.

BACKGROUND: Syringomyelia (SM) and myxomatous mitral valve disease (MMVD) are highly prevalent in Cavalier King Charles spaniels (CKCS). Cardiac status in CKCS with and without SM is currently unknown. OBJECTIVES: To investigate the association between SM and MMVD severity in CKCS and CKCS with SM with and without clinical signs of SM. ANIMALS: Fifty-five CKCS: 40 with SM (22 symptomatic and 18 asymptomatic) and 15 without SM. METHODS: A combined retrospective and prospective study. MRI and echocardiography were used to diagnose SM and MMVD, respectively. The association between SM and MMVD severity (left ventricle internal diameter in diastole normalized to bodyweight [LVIDDN] and left atrium to aortic ratio [LA/Ao]) were tested using multivariable linear regression analysis adjusting for sex and age. RESULTS: Overall, no significant difference in LVIDDN and LA/Ao was found between CKCS with or without SM. However, CKCS with symptomatic SM had significantly smaller LVIDDN (1.45 [1.30-1.50]) (median [IQR]) and LA/Ao (1.20 [1.10-1.28]) compared to CKCS with asymptomatic SM (1.60 [1.50-1.90] and 1.40 [1.20-1.75]) as well as CKCS without SM (0.24 [0.03-0.45] and 0.30 [0.05-0.56]) (all P values <.03). CONCLUSIONS AND CLINICAL IMPORTANCE: An association between MMVD and SM was not confirmed in this cohort of CKCS, indicating that MMVD and SM do not co-segregate. However, CKCS with symptomatic SM had smaller left ventricle and atrial size compared to CKCS with asymptomatic SM and CKCS without SM.

Estimation of separable direct and indirect effects in continuous time.

Many research questions involve time-to-event outcomes that can be prevented from occurring due to competing events. In these settings, we must be careful about the causal interpretation of classical statistical estimands. In particular, estimands on the hazard scale, such as ratios of cause-specific or subdistribution hazards, are fundamentally hard to interpret causally. Estimands on the risk scale, such as contrasts of cumulative incidence functions, do have a clear causal interpretation, but they only capture the total effect of the treatment on the event of interest; that is, effects both through and outside of the competing event. To disentangle causal treatment effects on the event of interest and competing events, the separable direct and indirect effects were recently introduced. Here we provide new results on the estimation of direct and indirect separable effects in continuous time. In particular, we derive the nonparametric influence function in continuous time and use it to construct an estimator that has certain robustness properties. We also propose a simple estimator based on semiparametric models for the two cause-specific hazard functions. We describe the asymptotic properties of these estimators and present results from simulation studies, suggesting that the estimators behave satisfactorily in finite samples. Finally, we reanalyze the prostate cancer trial from Stensrud et al. (2020).

Development of upper gastrointestinal cancer in patients with symptomatic gallstones, cholecystectomy, and sphincterotomy: A nationwide cohort study.

BACKGROUND AND OBJECTIVE: Exposures of gallstones and treatments thereof in relation to development of cancer have not been explored before in long-term follow-up studies. Our objective was to determine whether symptomatic gallstones, cholecystectomy, or sphincterotomy were associated with development of upper gastrointestinal cancers. METHODS: This is a nationwide cohort study of persons born in Denmark 1930-1984 included from age 30 years with long-term follow-up (1977-2014). Exposures were hospital admissions with gallstones, cholecystectomy, and sphincterotomy. Time-varying covariates were included in analyses to allow the impact of exposures to change with time. Follow-up periods were 2-5 and > 5 years. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. RESULTS: A total of 4,465,962 persons were followed. We found positive associations between sphincterotomy and biliary (>5 years HR 4.34, CI [2.17-8.70]), gallbladder (2-5 years HR 20.7, CI [8.55-50.1]), and pancreatic cancer (2-5 years HR 3.68, CI [2.09-6.49]). Cholecystectomy was positively associated with duodenal (2-5 years HR 2.94, CI [1.31-6.58]) and small bowel cancer (2-5 years HR 2.75, CI [1.56-4.87]). Inverse associations were seen for cholecystectomy and biliary (>5 years HR 0.60, CI [0.41-0.87]), pancreatic (>5 years HR 0.45 CI [0.35-0.57]), esophageal (>5 years HR 0.57, CI [0.43-0.74]), and gastric cancer (>5 years HR 0.68, CI [0.55-0.86]) and for gallstones and pancreatic cancer (>5 years HR 0.66, CI [0.47-0.93]). Gallstones were positively associated with gallbladder (>5 years HR 3.51, CI [2.02-6.10]) and small bowel cancer (2-5 years HR 3.21, CI [1.60-6.45]). CONCLUSIONS: A positive association between sphincterotomy and biliary cancer was identified. Cholecystectomy seems to be inversely associated with biliary, pancreatic, esophageal, and gastric cancer. Associations should be explored in similar large cohorts.

Pharmacokinetics of Repeated Oral Dosing with Coenzyme Q10 in Cavalier King Charles Spaniels with Myxomatous Mitral Valve Disease.

Coenzyme Q10 (Q10) is a mitochondrial cofactor and an antioxidant with the potential to combat oxidative stress in heart failure. This study aims to determine the pharmacokinetics of repeated oral dosing of Q10 in Cavalier King Charles Spaniels (CKCS) with spontaneous myxomatous mitral valve disease (MMVD) and to evaluate echocardiographic parameters, circulating cardiac biomarkers, and quality of life (QoL) after treatment. The study is a randomized, placebo-controlled, single-blinded crossover study. Nineteen CKCS with MMVD were randomized to receive 100 mg Q10 (ubiquinone) bi-daily for three weeks, then placebo (or in reverse order). Clinical examination, blood sampling, echocardiography, and QoL assessment were performed before and after each treatment phase. Q10 plasma concentrations were determined in plasma using a validated high-performance liquid chromatography method using electrochemical detection (HPLC-ECD). Eighteen CKCS were included in the analyses. Total plasma concentration of Q10 increased significantly (p < 0.0001) from baseline (median, 0.92 µg/mL; interquartile range (IQR), 0.70-1.26) to after treatment (median, 3.51 µg/mL; IQR, 2.30-6.88). Thirteen dogs reached the threshold of a total plasma Q10 concentration of ≥2.0 µg/mL. The average half-life (T1/2) of Q10 was 2.95 days (IQR, 1.75-4.02). No significant differences were observed in clinical MMVD severity, and the owner perceived QoL between Q10 and placebo treatment. The solubilized Q10 formulation was well-tolerated in the dogs. Individual variation in plasma concentrations was observed following oral treatment. A long-term placebo-controlled trial is warranted in dogs with MMVD to determine long-term efficacy on the clinical severity of MMVD.

Instrumental variables estimation with competing risk data.

Time-to-event analyses are often plagued by both-possibly unmeasured-confounding and competing risks. To deal with the former, the use of instrumental variables (IVs) for effect estimation is rapidly gaining ground. We show how to make use of such variables in competing risk analyses. In particular, we show how to infer the effect of an arbitrary exposure on cause-specific hazard functions under a semi-parametric model that imposes relatively weak restrictions on the observed data distribution. The proposed approach is flexible accommodating exposures and IVs of arbitrary type, and enabling covariate adjustment. It makes use of closed-form estimators that can be recursively calculated, and is shown to perform well in simulation studies. We also demonstrate its use in an application on the effect of mammography screening on the risk of dying from breast cancer.

Efficacy of laser treatment for onychomycotic nails: a systematic review and meta-analysis of prospective clinical trials.

Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A systematic review and one-arm meta-analysis, including all prospective clinical trials, identified on PubMed, Cochrane Library, and EMBASE databases. Trials with participants as unit of analysis (UOA), n = 13, were analyzed separately from trials with nails as UOA, n = 7. Summary proportions and 95% confidence intervals (95% CI) were calculated. Outcomes were mycological cure, clinical improvement, or complete cure. Twenty-two prospective trials (four randomized controlled trials and 18 uncontrolled trials) with a total of 755 participants were analyzed. Summary proportions with 95% CI for participants as UOA were mycological cure 70.4%, 95% CI 52.2-83.8%; clinical improvement 67.2%, 95% CI 43.2-84.7%; and complete cure 7.2%, 95% CI 1.9-23.5%. High statistical heterogeneity was detected (mycological cure I2 = 88%, P < 0.01; clinical improvement I2 = 69%, P < 0.01; complete cure I2 = 60%, P = 0.11). The current level of evidence is limited and with high heterogeneity, making it difficult to assess the true efficacy of laser treatment for onychomycosis. Larger randomized controlled trials with well-defined methodology are warranted.

Calcitonin-gene related peptide and disease activity in cluster headache.

OBJECTIVE: To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks. METHODS: We included patients with episodic cluster headache in an active phase (n = 9), episodic cluster headache patients in remission (n = 9) and patients with chronic cluster headache (n = 13). Cluster headache attacks were induced by infusion of calcitonin gene-related peptide (1.5 µg/min) in a randomized, double-blind, placebo controlled, two-way cross-over study. At baseline, we collected interictal blood samples from all patients and during 11 calcitonin gene-related peptide-induced cluster headache attacks. RESULTS: At baseline, episodic cluster headache patients in remission had higher plasma levels of calcitonin gene-related peptide, 100.6 ± 36.3 pmol/l, compared to chronic cluster headache patients, 65.9 ± 30.5 pmol/l, ( p = 0.011). Episodic cluster headache patients in active phase had higher PACAP38 levels, 4.0 ± 0.8 pmol/l, compared to chronic cluster headache patients, 3.3 ± 0.7 pmol/l, ( p = 0.033). Baseline levels of vasoactive intestinal polypeptide did not differ between cluster headache groups. We found no attack-related increase in calcitonin gene-related peptide, PACAP38 or vasoactive intestinal polypeptide levels during calcitonin gene-related peptide-induced cluster headache attacks. CONCLUSIONS: This study suggests that cluster headache disease activity is associated with alterations of calcitonin gene-related peptide expression. Future studies should investigate the potential of using calcitonin gene-related peptide measurements in monitoring of disease state and predicting response to preventive treatments, including response to anti-calcitonin gene-related peptide monoclonal antibodies.

Instrumental variables estimation under a structural Cox model.

Instrumental variable (IV) analysis is an increasingly popular tool for inferring the effect of an exposure on an outcome, as witnessed by the growing number of IV applications in epidemiology, for instance. The majority of IV analyses of time-to-event endpoints are, however, dominated by heuristic approaches. More rigorous proposals have either sidestepped the Cox model, or considered it within a restrictive context with dichotomous exposure and instrument, amongst other limitations. The aim of this article is to reconsider IV estimation under a structural Cox model, allowing for arbitrary exposure and instruments. We propose a novel class of estimators and derive their asymptotic properties. The methodology is illustrated using two real data applications, and using simulated data.

Instrumental variables estimation of exposure effects on a time-to-event endpoint using structural cumulative survival models.

The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental variables in observational studies that incorporate elements of randomization, either by design or by nature (e.g., random inheritance of genes). Instrumental variables estimation of exposure effects is well established for continuous outcomes and to some extent for binary outcomes. It is, however, largely lacking for time-to-event outcomes because of complications due to censoring and survivorship bias. In this article, we make a novel proposal under a class of structural cumulative survival models which parameterize time-varying effects of a point exposure directly on the scale of the survival function; these models are essentially equivalent with a semi-parametric variant of the instrumental variables additive hazards model. We propose a class of recursive instrumental variable estimators for these exposure effects, and derive their large sample properties along with inferential tools. We examine the performance of the proposed method in simulation studies and illustrate it in a Mendelian randomization study to evaluate the effect of diabetes on mortality using data from the Health and Retirement Study. We further use the proposed method to investigate potential benefit from breast cancer screening on subsequent breast cancer mortality based on the HIP-study.

Wound healing and all-cause mortality in 958 wound patients treated in home care.

Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.

The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation.

BACKGROUND: An important limitation to the success of lung transplantation is the development of bronchiolitis obliterans syndrome (BOS). It has been hypothesized that regulatory T lymphocytes (Tregs) are related to the risk of BOS. We aim to evaluate whether the number of forkhead box P3 (FoxP3+) cells/mm(2) in lung allograft biopsies is a predictor of long-term outcome. MATERIALS AND METHODS: A total of 58 consecutive lung transplant patients were included in the study. For 233 routine surveillance biopsy samples, the numbers of FoxP3+ cells/mm(2) were assessed by immunohistochemical staining with antibodies against FoxP3. BOS scores were calculated for the first five yr after transplantation. RESULTS: We determined that acute rejection was related to the time elapsed from transplantation to BOS with hazard ratios of 3.18 (p = 0.02) and 3.73 (p = 0.04) when comparing the levels of acute rejection grade 1 and grade 2/3, respectively, to no rejection. According to a Cox regression analysis, the number of FoxP3+ cells/mm(2) was not predictive of time to BOS. DISCUSSION AND CONCLUSIONS: Our data indicate that the number of FoxP3+ cells in the lung allograft did not correlate with BOS-free survival time. Previous studies have been contradictory and included different time points. Our findings emphasize the importance of including a time factor.

Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes.

BACKGROUND: Regulatory T lymphocytes (Tregs) play an important role in acute rejection after lung transplantation. However, the importance of the time elapsed after transplantation on the Treg response requires further investigation. We aim to evaluate the change over time in the frequency of Tregs in lung allograft biopsies and to assess how Tregs relate to simultaneous and subsequent acute cellular rejection. MATERIALS AND METHODS: A total of 258 biopsy samples obtained 0.5, 1, 3, 12 and 24 months after transplantation from 58 consecutive lung transplant patients were included. The biopsies were scored for acute rejection according to the ISHLT criteria (A0-A4) and immunohistochemically stained with antibodies against FoxP3. RESULTS: There was a tendency for a decrease in the number of Tregs/mm2 with time. However, the previous levels of Tregs/mm2 did not have any significant effect on future levels of Tregs/mm2. For biopsies taken 0.5 and 1 month after transplantation, a significant correlation between Tregs/mm2 and the degree of acute rejection was found, and logistic regression analysis using updated values for Tregs/mm2 showed a significant relationship between Tregs/mm2 at 2 weeks and an A-score≥2 after 1 and 3 months. At later time points, this correlation disappeared. DISCUSSION AND CONCLUSION: Our data indicate that the time elapsed after transplantation is an important parameter influencing the Treg response after lung transplantation. This observation is in accordance with studies indicating a narrow therapeutic window for induction of tolerance by specifically targeting T-cells. The results also indirectly indicate that Tregs early after transplantation could have an impact on the long-term outcome.

Determinants of developmental coordination disorder in 7-year-old children: a study of children in the Danish National Birth Cohort.

AIM: The aim of this study was to investigate early life determinants of developmental coordination disorder (DCD) in 7-year-old children. METHOD: The study was based on data from 33,354 women and their children who participated in the 7-year follow-up study of the Danish National Birth Cohort. Information on several potential determinants (maternal age at conception, maternal occupational status, smoking and alcohol consumption during pregnancy, child's sex, intrauterine growth restriction, degree of preterm birth, and age at walking) was obtained from population registries, from interviews during pregnancy and when the child was 18 months old. The outcome in this study was DCD at 7 years of age, measured by the validated Developmental Coordination Disorder Questionnaire. The associations between the potential determinants and DCD were estimated using logistic regression. RESULTS: The study population consisted of 17,065 males and 16,289 females (141 [0.4%] born very preterm [23(+0)-31(+6) wk]; 1281 [3.8%] born moderately preterm [32(+0)-36(+6) wk]; 29,044 [87.1%] were born term [37(+0)-41(+6) wk], and 2888 [8.7%] were born post-term [≥ 42(+0) wk]). Independently of each other, the following determinants were predictors of DCD: being a female (odds ratio [OR] 0.36 [95% confidence interval {CI} 0.31-0.41]); being born very preterm (OR 6.28 [95% CI 3.99-9.89]) or moderately preterm (OR 2.10 [95% CI 1.65-2.67]); being small for gestational age (OR 1.74 [95% CI 1.46-2.08]); being 15 months of age or more at walking attainment (OR 3.05 [95% CI 2.57-3.60]); and maternal occupational status (higher grade professionals (OR 1.28 [95% CI 1.02-1.61); economically inactive (OR 1.43 [95% CI 1.07-1.91]). Young maternal age and smoking were risk factors among term-born children. INTERPRETATION: The risk of DCD increases with decreasing gestational age. Intrauterine growth restriction is also a strong risk factor, as well as delayed walking.

Reproducibility of mass spectrometry based protein profiles for diagnosis of ovarian cancer across clinical studies: A systematic review.

The focus of this systematic review is to give an overview of the current status of clinical protein profiling studies using MALDI and SELDI MS platforms in the search for ovarian cancer biomarkers. A total of 34 profiling studies were qualified for inclusion in the review. Comparative analysis of published discriminatory peaks to peaks found in an original MALDI MS protein profiling study was made to address the key question of reproducibility across studies. An overlap was found despite substantial heterogeneity between studies relating to study design, biological material, pre-analytical treatment, and data analysis. About 47% of the peaks reported to be associated to ovarian cancer were also represented in our experimental study, and 34% of these redetected peaks also showed a significant difference between cases and controls in our study. Thus, despite known problems related to reproducibility an overlap in peaks between clinical studies was demonstrated, which indicate convergence toward a set of common discriminating, reproducible peaks for ovarian cancer. The potential of the discriminating protein peaks for clinical use as ovarian cancer biomarkers will be discussed and evaluated. This article is part of a Special Issue entitled: Proteomics: The clinical link.

The Sino-Nasal Outcome Test 22 validated for Danish patients.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a significant health problem whose incidence and prevalence is rising. It calls into attention consensus about diagnosing, assessing symptoms and treatment of patients with CRS. Therefore, a validated Danish measure of health-related quality of life in sinonasal disease is needed. MATERIAL AND METHODS: The Sino-Nasal Outcome Test 22 (SNOT-22) was translated into Danish and its reproducibility was evaluated by test-retesting 40 patients with CRS. The statistical analyses used were Pearson's correlation coefficient, Cronbach's alpha, kappa and Bland-Altman's plot. Reproducibility was also tested for SNOT-22 subscales. RESULTS: The results show good internal correlation with a Cronbach's alpha of 0.83 in the initial test and one of 0.92 in the retest. Pearson's correlation coefficient was 0.70 (p < 0.001), revealing good correlation between the initial scores and the retests scores. Kappa was calculated for each item with a mean value of 0.61 showing substantial agreement. The paired t-test revealed no significant difference between the subscales. CONCLUSION: The Danish version of SNOT-22 is recommended for Danish clinicians and researchers as a patient-reported measure of outcome in sinonasal disorders such as rhinosinusitis and nasal polyposis.

Flexible survival regression modelling.

Regression analysis of survival data, and more generally event history data, is typically based on Cox's regression model. We here review some recent methodology, focusing on the limitations of Cox's regression model. The key limitation is that the model is not well suited to represent time-varying effects. We start by considering classical and also more recent goodness-of-fit procedures for the Cox model that will reveal when the Cox model does not capture important aspects of the data, such as time-varying effects. We present recent regression models that are able to deal with and describe such time-varying effects. The introduced models are all applied to data on breast cancer from the Norwegian cancer registry, and these analyses clearly reveal the shortcomings of Cox's regression model and the need for other supplementary analyses with models such as those we present here.

Acute phase response to surgery of varying intensity in horses: a preliminary study.

OBJECTIVE: To evaluate the postoperative inflammatory response of horses to elective surgery of varying intensity. STUDY DESIGN: Prospective longitudinal study. ANIMALS: Horses referred to 2 hospitals for either arthroscopic removal of a unilateral osteochondritic lesion in the tibiotarsal joint (minimal surgical trauma, n=11), correction of recurrent laryngeal neuropathy by laryngoplasty and ventriculectomy (intermediate surgical trauma, n=10) or removal of an ovarian tumor by laparotomy (major surgical trauma, n=5). METHODS: Horses had a thorough clinical examination every day. White blood cell (WBC) counts and concentrations of serum amyloid A (SAA), fibrinogen, and iron were assessed in blood samples obtained before, and 1-3, 5, 7, 9, and 11 days after surgery. Differences in levels of the inflammatory markers between the 3 surgical groups were analyzed using repeated measures ANOVA. RESULTS: Postoperative concentrations of SAA and fibrinogen were significantly higher in horses that had laparotomy and ovariectomy than in horses that had laryngoplasty and ventriculectomy, or arthroscopy. Iron concentrations decreased to lower levels after intermediate and major surgical trauma than after small surgical trauma. WBC count did not differ between the 3 groups. CONCLUSIONS: Levels of SAA, fibrinogen, and iron reflected the intensity of the surgical trauma, whereas WBC count did not. CLINICAL RELEVANCE: Postoperative measurements of SAA, fibrinogen, and iron may be useful for comparing surgical trauma associated with new and established surgical techniques. Moreover, knowledge of the normal postoperative acute phase response is essential, if acute phase reactants are to be used for monitoring occurrence of postoperative infections.

The additive hazards model with high-dimensional regressors.

This paper considers estimation and prediction in the Aalen additive hazards model in the case where the covariate vector is high-dimensional such as gene expression measurements. Some form of dimension reduction of the covariate space is needed to obtain useful statistical analyses. We study the partial least squares regression method. It turns out that it is naturally adapted to this setting via the so-called Krylov sequence. The resulting PLS estimator is shown to be consistent provided that the number of terms included is taken to be equal to the number of relevant components in the regression model. A standard PLS algorithm can also be constructed, but it turns out that the resulting predictor can only be related to the original covariates via time-dependent coefficients. The methods are applied to a breast cancer data set with gene expression recordings and to the well known primary biliary cirrhosis clinical data.

Comparison of B-mode and Doppler ultrasonographic findings with histologic features of benign and malignant superficial lymph nodes in dogs.

OBJECTIVE: To compare and correlate B-mode and color Doppler ultrasonographic characteristics with histopathologic findings of benign and malignant superficial lymph nodes in dogs. STUDY POPULATION: 50 superficial lymph nodes that were normal, abnormally large on physical examination, or represented regional lymph nodes draining an area of suspected primary malignancy in 30 dogs. PROCEDURES: Before excision, lymph nodes were evaluated via B-mode and color Doppler ultrasonography to assess size, echogenicity, presence of a hilus, acoustic transmission, and vascular flow. Formalin-fixed, paraffin-embedded tissue sections of excised lymph nodes were stained with H&E and examined for the presence and extent of necrosis, fibrosis, fat, metastases, and tissue heterogeneity. To assess vascularity, the number and distribution of vessels stained by the Verhoeff van Gieson technique were recorded. RESULTS: In superficial lymph nodes, a varied echogenicity corresponded to tissue heterogeneity. The ultrasonographic detection of a hilus was associated with the presence of fibrous tissue, fat, or both in the hilar region. Acoustic enhancement corresponded to presence of areas of intranodal necrosis. There was significant correlation between both the distribution and the number of vessels detected via ultrasonography and that detected by histopathology. The amount of flow estimated via ultrasonography was typically higher than that estimated via histologic examination. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that histopathologic changes in canine lymph nodes have associated ultrasonographic changes and suggest that lymph node ultrasonography has an important role in the evaluation of lymph nodes in dogs in general and in dogs with neoplastic disease in particular.

Comparison of B-mode and Doppler ultrasonographic findings with histologic features of benign and malignant mammary tumors in dogs.

OBJECTIVE: To compare and correlate B-mode and color Doppler ultrasonographic characteristics with the histologic findings of benign and malignant mammary tumors in dogs. STUDY POPULATION: 49 mammary tumors in 26 dogs. PROCEDURES: Before excision, tumors were evaluated via B-mode and color Doppler ultrasonography to assess size, echogenicity, echopattern, acoustic transmission, invasiveness, and vascularity. Paraffin-embedded microsections of the tumors were stained with H&E and examined for presence of necrosis, cysts, cartilage, bone, mineralization, invasion of surrounding tissue, and tissue heterogeneity. To assess vascularity, the number and distribution of vessels that were stained by the Verhoeff van Gieson technique were recorded. RESULTS: Tumor echogenicity and echopattern on ultrasonographic images correlated with tissue heterogeneity detected histologically. Acoustic enhancement was correlated with the presence of necrotic or cystic areas. Tumor invasion into surrounding tissues as determined ultrasonographically did not correlate with the histologic findings. There was a significant correlation between the number of detected vessels and distribution of flow within the tumors determined via ultrasonographic and histologic examinations. CONCLUSIONS AND CLINICAL RELEVANCE: In canine mammary tumors, ultrasonographic characteristics appear to be correlated with histopathologic changes. Data suggest that ultrasonography may have an important role in the evaluation of mammary tumors in dogs, particularly in the evaluation of tissue composition and tumor vascularity.