Phase 2 study of cabazitaxel as second-line treatment in patients with HER2-negative metastatic breast cancer previously treated with taxanes-a Hellenic Cooperative Oncology Group (HeCOG) Trial.

BACKGROUND: Cabazitaxel is a novel taxane that might be active in breast cancer resistant to first-generation taxanes. METHODS: The purpose of the current multicentre phase II trial was to evaluate the activity and safety of cabazitaxel, as second-line treatment, in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with taxanes. The primary endpoint was objective response rate (ORR). RESULTS: Eighty-four patients were enrolled between October 2012 and November 2016. Taxane resistance to previous treatment was detected in 43 cases. The ORR was 22.6% in the intent-to-treat population, 23.3% in taxane-resistant and 20.5% in taxane-non-resistant cases. At a median follow-up of 39.6 months, the median progression-free survival and overall survival were 3.7 months (95% CI 2.2-4.4) and 15.2 months (95% CI 11.3-19.4), respectively. Regarding toxicity, grade 3-4 neutropenia was reported in 22.6% and febrile neutropenia in 6% of the patients, respectively. Two fatal events (one febrile neutropenia and one sepsis) were reported as being related to study treatment. CONCLUSIONS: This phase II trial suggests that cabazitaxel is active as second-line treatment in taxane-pretreated patients with HER2-negative MBC, with manageable toxicity.

A comparative study of color Doppler imaging and contrast-enhanced ultrasound for the detection of ulceration in patients with carotid atherosclerotic disease.

OBJECTIVES: To evaluate the diagnostic accuracy of color Doppler imaging (CDI) and contrast-enhanced ultrasound (CEUS) for diagnosing carotid ulceration, having multi-detector computed tomography angiography (MDCTA) as the reference method. METHODS: Patients with carotid disease referred for ultrasound (US), either due to the occurrence of neurovascular symptoms or for screening purposes, were included in this study if at least one plaque causing moderate (50-69%) or severe (70-99%) internal carotid artery stenosis was detected. Carotid US with CDI technique, CEUS, and MDCTA were performed in all patients, investigating the presence of ulceration. The agreement between modalities was evaluated using kappa statistics. RESULTS: The study population included 54 patients (median age 62 years, inter-quartile range 16.2) and 66 carotid arteries. The mean degree of stenosis was 68.5% (SD 12.2%) while 47.1% of plaques were symptomatic. MDCTA characterized 28.8% of plaques as smooth, 45.5% irregular, and 24.3% ulcerated. Flow reversal was detected with CDI in 65.5% of ulcerations, while swirling of the microbubbles and neovessels adjacent to the ulcer were detected with CEUS in 17.64%. The agreement for ulceration diagnosis was moderate between CDI and CEUS (kappa 0.473) and between CDI and MDCTA (kappa 0.473) and very good between CEUS and MDCTA (kappa 0.921). The sensitivity, specificity, and positive and negative predictive values of CDI for the diagnosis of ulceration were 41.2%, 97.95%, 87.5%, 82.8% respectively, while CEUS respective measures were 94.1%, 97.95%, 94.1%, and 97.95%. CONCLUSION: CEUS outperformed CDI in terms of agreement with MDCTA and diagnostic accuracy for the diagnosis of ulcerated carotid plaque. KEY POINTS: • Superficial ulceration is a significant feature of carotid plaque vulnerability. • Color Doppler imaging has the potential to demonstrate carotid plaque ulceration but is characterized by limited sensitivity and moderate agreement with the reference method of multi-detector computed tomography angiography. • Contrast-enhanced ultrasound outperforms color Doppler imaging in terms of sensitivity for the detection of carotid plaque ulceration and in agreement with the reference method of multi-detector computed tomography angiography.

Does Quantification of Carotid Plaque Surface Irregularities Better Detect Symptomatic Plaques Compared to the Subjective Classification?

OBJECTIVES: To evaluate the interobserver agreement of color Doppler ultrasound (CDUS) and contrast-enhanced ultrasound (CEUS) for quantification of carotid plaque surface irregularities and to correlate objective and subjective measures with stroke occurrence. METHODS: This work was an observational study involving 54 patients with 62 internal carotid artery or carotid bulb plaques (31 symptomatic) undergoing CDUS and CEUS between February 2016 and February 2018, with retrospective interpretation of prospectively acquired data. Plaques were included if causing moderate (50%-69%) or severe (70%-99%) stenosis based on velocity criteria, and their surface was classified as smooth, irregular, or ulcerated based on CEUS. The surface irregularities were quantified in the form of a surface irregularity index by 2 observers, based on CDUS and CEUS. The surface irregularity index was evaluated for interobserver agreement with CDUS and CEUS and correlated with the occurrence of stroke, as was the subjective characterization of the plaque surface. RESULTS: Color Doppler ultrasound and CEUS showed good interobserver agreement (intraclass correlation coefficients, 0.979 and 0.952, respectively). Plaques were characterized as smooth in 30.6% of cases, irregular in 50%, and ulcerated in 19.4%. The subjective classification of the plaque surface did not correlate with stroke occurrence (P > .05, χ2 ). Surface irregularity index values were significantly higher for symptomatic plaques with both CDUS and CEUS (P < .05). CONCLUSIONS: Color Doppler ultrasound and CEUS can quantify carotid plaque surface irregularities with good interobserver agreement. The resulting quantitative measure was significantly higher in symptomatic plaques, whereas the subjective characterization of plaque surface failed to differ between symptomatic and asymptomatic plaques.

Extracranial internal carotid artery occlusive dissection - multimodality presentation in a case series.

Background: Carotid dissection is a rare disease, mainly affecting young and middle-aged patients potentially ending up in stroke. Multimodality imaging plays an essential role, both in terms of prompt and accurate diagnosis and follow-up of this entity. Patients and methods: We herein present a case series of patients with internal carotid artery dissection and compare the various imaging findings of ultrasonography, multidetector computed tomography angiography and magnetic resonance angiography, with a purpose to illustrate the value of multimodality imaging in the diagnosis of carotid dissection. Results: Ultrasound represents the first-line imaging modality for the evaluation of a suspected carotid pathology. Digital subtraction angiography is considered the gold standard method for evaluation of carotid luminal abnormalities and is currently reserved for those patients selected for endovascular surgery. Nevertheless, the widespread availability of modern cross-sectional techniques such as multi-detector computed tomography angiography and magnetic resonance angiography has made angiography marginalised. Computed tomography and magnetic resonance angiography offered accurate delineation of vascular lumen and providing valuable information for the vascular wall composition. Conclusions: Careful interpretation of imaging findings on various imaging modalities can lead to early and accurate diagnosis of carotid dissection.

Longitudinal Evaluation of Swallowing with Videofluoroscopy in Patients with Locally Advanced Head and Neck Cancer After Chemoradiation.

The aim of this study was to investigate the prevalence, severity, and pattern of evolution of swallowing impairments encountered in head and neck cancer (HNC) patients before and after chemoradiation (CRT) with videofluoroscopy of swallowing study (VFSS), using the modified barium swallow impairment profile (MBSImP) protocol and scoring system, and to determine the appropriate time points in which these patients should undergo VFSS post-CRT. A prospective cohort of 69 patients with locally advanced HNC underwent VFSS with the MBSImP protocol at 5 evaluation points: pre-CRT, and 1, 3, 6, and 12 months post-CRT. VFSS was scored with MBSImP, penetration-aspiration scale (PAS), and swallowing performance status (SPS) scale. Statistical analysis was performed only for the 12-month disease-free subset of patients. MBSImP, PAS, and SPS scale scores reached their peak at 3 months post-CRT and improved at 6-12 months, but without returning at pre-treatment levels. Base of tongue retraction, initiation of pharyngeal swallow, epiglottic movement, laryngeal vestibule closure, and laryngeal elevation were the most frequently observed impaired MBSImP components. Epiglottic movement significantly improved (p = 0.009) and laryngeal vestibule closure significantly deteriorated (p = 0.042) over time (Friedman test). Severe swallowing deficits and high aspiration rates are observed in HNC patients pre-CRT, which further deteriorate post-CRT, peak at 3 months, and despite slight improvement, persist over time. We suggest that these patients, regardless of the presence of subjective dysphagia, should undergo VFSS both before and 3 months post-CRT, and also if possible, 1 month post-CRT, in order to facilitate implementation of early swallowing rehabilitation.

Bone Quality Assessment as Measured by Trabecular Bone Score in Patients With End-Stage Renal Disease on Dialysis.

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder.

ASSESSMENT OF SENTINEL LYMPH NODE METASTASIS IN CANINE MAMMARY GLAND TUMORS USING COMPUTED TOMOGRAPHIC INDIRECT LYMPHOGRAPHY.

In the staging process of the breast cancer, demonstrating metastasis of the sentinel lymph node (SLN) has an important prognostic value, in both humans and animals. The aim of this prospective case-control study was to determine the diagnostic value of computed tomographic indirect lymphography (CT-LG) for detecting SLN metastasis in dogs with mammary cancer. Thirty-three female dogs with tumors in the abdominal and inguinal mammary glands were prospectively selected and subjected to CT-LG, 1 and 5 min after injection of 1 ml of contrast agent (iopamidol) in the subareolar tissue of the neoplastic and the contralateral normal mammary glands. The pattern of postcontrast opacification, degree of postcontrast enhancement, and size and shape were assessed in 65 SLNs in total and were correlated with histopathological findings. The absence of opacification or heterogeneous opacification 1 min after contrast medium injection showed the highest sensitivity, specificity, and accuracy (93%, 100%, and 98.4%, respectively). In images taken 1 min after injection, an absolute density value lower than 444 Hounsfield units (HU) in the center of the SLN also provided significant sensitivity and specificity (93.8% and 75%, respectively). The size and shape of the SLN (maximum and minimum diameter, maximum/minimum diameter ratio, maximum diameter/height of fifth thoracic vertebral body ratio) showed the lowest sensitivity and specificity. Results of this study support the hypothesis that CT-LG could help in the assessment of SLN metastasis in cases of mammary gland tumors in dogs.

Multiple variations of the coeliac axis, hepatic and renal vasculature as incidental findings illustrated by MDCTA.

Vascular anatomical variations are not uncommon and may affect any organ's arterial or venous vasculature. The coexistence of variations in different organic systems is less commonly found, but of great clinical significance in a series of clinical conditions like organ transplantation and surgical preoperative planning. Multidetector computed tomography angiography (MDCTA) has emerged as a valuable alternative to the conventional angiography for accurate evaluation of vascular anatomy and pathology. Radiologists should be familiar with each organ's vascular variations and always report them to the clinician, even if they represent an incidental finding. This case report presents a 52-year-old female patient undergoing abdominal MDCTA for characterization of a renal lesion. This examination revealed the presence of three hilar arteries on the left kidney, a main renal vein in combination with an additional renal vein in both sides along with a replaced right hepatic artery originating from the superior mesenteric artery. Moreover, both inferior phrenic arteries were found originating from the coeliac axis. 3D volume rendering technique images were used in the evaluation of vascular anatomy as illustrated in this case report.

Role of multi-parametric ultrasound in transient perivascular inflammation of the carotid artery syndrome.

INTRODUCTION: The term "carotidynia" has been used to describe a symptom or a nosologic entity characterized by pain in the lateral neck region and over the carotid bifurcation. Recent advances in diagnostic imaging and the introduction of diagnostic criteria have led to the adoption of term "Transient perivascular inflammation of the carotid artery" (TIPIC) syndrome. METHOD: A retrospective analysis of the Radiology Department's database was performed to identify cases with the diagnosis of TIPIC syndrome. The purpose was to identify ultrasound images including B-mode technique, colour, power Doppler technique and contrast-enhanced ultrasound (CEUS). FINDINGS: In total, five patients with the diagnosis of TIPIC syndrome are presented in this review. TIPIC syndrome is a clinic-radiologic entity characterized by pain over the carotid area, a symptom referring to a wide differential diagnosis where imaging plays a crucial role for proper diagnosis and treatment. Characteristic imaging findings on conventional ultrasound and CEUS are presented in this review. DISCUSSION: TIPIC syndrome can be investigated with virtually any imaging modality. Ultrasound typically reveals perivascular infiltration and a hypoechoic intimal plaque, while no significant luminal narrowing is appreciated. Computed tomography angiography and magnetic resonance angiography also demonstrate these vascular wall changes primarily affecting the distal common carotid artery, the carotid bulb and possibly the internal carotid artery proximal part. Contrast enhancement is a very characteristic and constant finding of TIPIC lesions, suggestive of the inflammatory nature of the disease and can be appreciated on computed tomography angiography and magnetic resonance angiography. CEUS has been recently used and successfully observed contrast enhancement of the lesions, similar to computed tomography angiography and magnetic resonance angiography. CONCLUSION: Ultrasound remains the first-line modality for the evaluation of TIPIC syndrome, capable of providing all the information needed, especially if supplemented with the administration of microbubbles so that the enhancement of lesions can be evaluated.

Contrast-enhanced ultrasound of the carotid system: a review of the current literature.

Carotid disease is a major current health problem accounting for a significant part of stroke patients. Ultrasound with colour Doppler and spectral analysis is the primary imaging technique used for screening and diagnostic evaluation of the extracranial part of carotid arteries offering identification and grading of carotid disease. However, inherent limitations of this technique include flow-related artefacts like Doppler angle dependence and aliasing artefact which may sometimes hinder complete assessment of a stenotic part of the vessel, potentially failing to address clinically significant differential diagnosis issues. The intravenous use of microbubbles as an US contrast agent has been introduced for the supplementation of conventional technique. The value of contrast-enhanced ultrasound (CEUS) has been investigated in the evaluation of carotid disease leading to promising results. CEUS provides improved flow visualization free of artefacts and detailed plaque surface delineation, thus being able to accurately grade stenosis, identify carotid plaque ulcerations, differentiate occlusion from highly stenotic plaques and identify carotid dissection. Furthermore, microbubbles can be used to identify and grade intraplaque neovascularization, carotid wall inflammation in patients with arteritis, follow-up patients after carotid intervention and assist interventional procedures reducing the need for nephrotoxic contrast agents. The purpose of this review is to present and discuss the current literature regarding the various uses of CEUS in carotid arteries.

Imaging of the ulcerated carotid atherosclerotic plaque: a review of the literature.

Carotid atherosclerotic disease constitutes a major modern health problem whose diagnosis primarily relies on imaging. Grading of stenosis has been long used as the main factor for risk stratification and guiding of management. Nevertheless, increasing evidence has shown that additional plaque characteristics such as plaque composition and surface morphology play an important role in the occurrence of symptoms, justifying the term "vulnerable plaque". Carotid plaque surface characteristics either in the form of surface irregularities or ulceration represent an important factor of vulnerability and are associated with the occurrence of neurologic symptoms. The delineation of the carotid plaque surface can be performed with virtually all imaging modalities including ultrasound, contrast-enhanced ultrasound, multi-detector computed tomography angiography, magnetic resonance angiography and the traditional reference method of angiography. These techniques have shown varying levels of diagnostic accuracy for the identification of ulcerated carotid plaques or plaque surface irregularities. As a consequence and given its high clinical significance, radiologists should be familiar with the various aspects of this entity, including its definition, classification, imaging findings on different imaging modalities and associations. The purpose of this review is to present the current literature regarding carotid plaque ulcerations and present illustrative images of ulcerated carotid plaques. TEACHING POINTS: • Plaque surface and ulceration represent risk factors for stroke in carotid disease. • Characterisation of the plaque surface and ulcerations can be performed with every modality. • US is the first-line modality for carotid disease and identification of ulcerations. • The administration of microbubbles increases US accuracy for diagnosis of carotid ulceration. • MDCTA and MRA are valuable for diagnosing ulceration and evaluating plaque composition.

Swirling of microbubbles: Demonstration of a new finding of carotid plaque ulceration on contrast-enhanced ultrasound explaining the arterio-arterial embolism mechanism.

Carotid plaque ulceration is a well-established feature of vulnerability, associated with high risk for neurological symptoms. From a pathogenetic point of view, the mechanism responsible for occurrence of symptomatology relies on the aggregation of platelets within the ulcer cavity, activation of coagulation mechanism, formation of thrombus and arterio-arterial embolization of thrombotic material in the central nervous system. Many imaging modalities including unenhanced ultrasound, computed tomographic angiography and magnetic resonance angiography have been used to image and diagnose carotid plaque ulceration with varying success. Contrast-enhanced ultrasound has been recently introduced in the study of carotid disease offering improved flow visualization and better plaque surface delineation. We present a case where contrast-enhanced ultrasound visualized the swirling pattern of movement of the microbubbles within the ulcer cavity. These findings illustrate the underlying hemodynamic mechanism of arterio-arterial embolization and can be proposed as a new finding of plaque ulcerations on contrast-enhanced ultrasound.

Computer assisted sound analysis of arteriovenous fistula in hemodialysis patients.

The purpose of this study was to reveal the unique sound characteristics of the bruit produced by arteriovenous fistulae (AVF), using a computerized method. An electronic stethoscope (20 Hz to 20 000 Hz sensitivity) was used, connected to a portable laptop computer. Forty prevalent hemodialysis patients participated in the study. All measurements were made with patients resting in supine position, prior to the initiation of mid-week dialysis session. Standard color Doppler technique was used to estimate blood flow. Clinical examination revealed the surface where the perceived bruit was more intense, and the recording took place at a sample rate of 22 000 Hz in WAV lossless format. Fast Fourier Transform (FFT) mathematical algorithm, was used for the sound analysis. This algorithm is particularly useful in revealing the periodicity of sound data as well as in mapping its frequency behavior and its strength. Produced frequencies were divided into 40 frequency intervals, 250 Hz apart, so that the results would be easier to plot and comprehend. The mean age of the patients was 63.5 ± 14 years; the median time on dialysis was 39.6 months (mean 1 month, max. 200 months). The mean blood flow was 857.7 ± 448.3 ml/min. The mean sound frequency was approximately 5 500 Hz ± 4 000 Hz and the median, which is also expressing the major peak of sound data, was 750 Hz, varying from 250 Hz to 10 000 Hz. A possible limitation of the study is the relatively small number of participants.

Radiographic and ultrasonographic findings of uterine neoplasms in nine dogs.

The records of nine female intact dogs with histologically confirmed uterine tumors were reviewed retrospectively, and the related radiographic and ultrasonographic signs of the lesions detected were recorded. Radiography revealed a soft-tissue opacity between the urinary bladder and colon in six of seven dogs with uterine body and/or cervical tumors, and a soft-tissue opacity in the midventral abdomen in two dogs with uterine horn tumors. Ultrasonography revealed masses in all dogs with uterine body/cervical tumors and could delineate the origin of the mass in one of two dogs with uterine horn tumors. The mass was characterized ultrasonographically as solid in three dogs (all leiomyomas), solid with cystic component in four dogs (two adenocarcinomas, one leiomyoma, and one fibroleiomyoma), and cystic in two (both leiomyomas). Hyperechoic foci in the mass were observed in three dogs. Ultrasonography was a useful method for demonstrating uterine body and/or cervical tumors. However, it was not possible to ascertain sonographically that a mass originated in a uterine horn unless there was associated evidence of uterine horn to which the mass could be traced. The ultrasonographic appearance of uterine tumors was variable, and the type of neoplasm could only be determined by taking biopsies of the mass.

The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: a randomized, placebo-controlled trial.

INTRODUCTION: Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease. The Homocysteine Lowering Trialists' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25%. Aim of this study was to investigate the effect of daily supplementation of folic acid (5 mg) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor. METHODS: We enrolled 103 patients with at least one cardiovascular risk factor who were randomized to receive either a daily dose of 5 mg folic acid (group I, n=53) or placebo (group II, n=50) for 18 months. RESULTS: After 18 months of folic acid supplementation, homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group. Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter. Significant regression of carotid IMT was observed (0.961+/-0.092 to 0.933+/-0.077 mm, p<0.001) compared to significant IMT progression in the placebo group (0.964+/-0.099 to 0.984+/-0.094 mm). CONCLUSION: Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk.

Homocysteine and carotid intima-media thickness in ischemic stroke patients are not correlated.

INTRODUCTION: Hyperhomocysteinemia has been linked to cardiovascular morbidity and mortality by numerous authors. Whether this association is causal or not remains uncertain. The aim of the study was to investigate the association of hyperhomocysteinemia with the degree of carotid atherosclerosis in stroke patients. METHODS: We studied 97 Greek patients in our stroke unit who were hospitalized as a result of ischemic stroke between March 2006 and May 2007. The patients were divided into two groups: the first (52 patients) included stroke patients with serum levels of homocysteine below 15 mumol/L, but in the second group (45 patients) serum homocysteine exceeded this value. We measured carotid intima-media thickness (cIMT) in all patients and correlated it with serum homocysteine. RESULTS: The mean homocysteine concentration was 11.5 mumol/L in the first group and 21.5 mumol/L in the second group. Carotid IMT was 1.012 mm in the first group, and 1.015 mm in the second group, an insignificant difference. On the contrary, serum folate concentration was 21.3 nmol/L in the first group compared with 16.7 nmol/L in the second group (p < 0.001). VitB12 was 401 pmol/L in the first group and 340 pmol/L in the second group, a statistically significant difference (p < 0.001). CONCLUSIONS: Serum levels of homocysteine were not correlated with cIMT in ischemic stroke patients. Both folate and vitB12 were decreased in hyperhomocysteinemic ischemic stroke patients.