Whole phenotype of patients with systemic sclerosis and sicca manifestations: Comparison with sicca manifestations from other causes.

INTRODUCTION & OBJECTIVES: This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes. METHODS: Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc). RESULTS: SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure. CONCLUSION: SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets.

Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial.

BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort. METHODS: In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters. RESULTS: This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters. CONCLUSIONS: Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency. TRIAL REGISTRATION: NCT00489697, registration number of the STIC-AVASTIN trial.

Visceral fat and clinical outcome in patients receiving first-line chemotherapy with bevacizumab for metastatic colorectal cancer.

BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.

Chest computed tomography signs associated with pejorative evolution in COVID-19 patients.

PURPOSE: The aim of this study was to evaluate how chest computed tomography (CT) can predict pejorative evolution in COVID-19 patients. MATERIAL AND METHODS: Data on 349 consecutive patients who underwent a chest CT either for severe suspected COVID-19 pneumonia or clinical aggravation and with COVID-19 were retrospectively analysed. In total, 109 had laboratory-confirmed COVID-19 infection by a positive reverse-transcription polymerase chain reaction (RT-PCR) and were included. The main outcomes for pejorative evolution were death and the need for invasive endotracheal ventilation (IEV). All the CT images were retrospectively reviewed, to analyse the CT signs and semiologic patterns of pulmonary involvement. RESULTS: Among the 109 COVID-19 patients, 73 (67%) had severe symptoms of COVID-19, 28 (25.7%) needed an IEV, and 11 (10.1%) died. The following signs were significantly associated with both mortality and need for IEV: traction bronchiectasis and total affected lung volume ≥ 50% (p < 10-3). Other CT signs were only associated with the need of IEV: vascular dilatation, air bubble sign, peribronchovascular thickening, interlobular thickening, and number of involved lobes ≥ 4 (p < 10-3). CONCLUSIONS: On a chest CT performed during the first week of the symptoms, the presence of traction bronchiectasis and high values of affected lung volume are associated with the need for IEV, and with mortality, in COVID-19 patients.

Concurrent losses of skeletal muscle mass, adipose tissue and bone mineral density during bevacizumab / cytotoxic chemotherapy treatment for metastatic colorectal cancer.

BACKGROUND: Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported. METHODS: Data were prospectively collected in a clinical study (NCT00489697) including patients with liver metastases of colorectal cancer who received 4 cycles of bevacizumab in combination with cytotoxic chemotherapy. Computerized tomography (CT) at baseline and after chemotherapy was used to quantify skeletal muscle and adipose tissue cross-sectional areas, and mean lumbar spine BMD using validated approaches. RESULTS: After exclusion of patients lacking adequate CT images or missing data, 72 subjects were included. Patients were 63% male, aged 63.2 ± 10.3 years, 100% had liver metastases and 54%, 24% and 22% respectively has 0, 1 and ≥2 extrahepatic metastases. 100% tolerated 4 cycles of treatment and none showed progressive disease at the end of treatment. The scan interval was 70 days (95% CI, 62.3 to 80.5). Thresholds for loss of tissue were defined as loss ≥ measurement error. 10% of patients showed no loss of any tissue and a further 43% lost one tissue (SMM, TAT or BMD); 47% of patients lost 2 tissues (16.5% lost SMM + TAT, 8% lost SMM + BMD, 10% lost TAT + BMD) or all 3 tissues (12.5%). Catabolic behavior (2 or 3 tissue loss vs 0 or 1 tissue loss) associated with disease burden, including unresectable primary tumor (p = 0.010), presence of extrahepatic (EH) metastases (p = 0.039) and number of EH metastases (p = 0.004). No association was found between the number of tissues lost and treatment response, which was uniformly high, or treatment toxicity, which was uniformly low. CONCLUSION: Multiple tissues can be measured in routine CT images and these show considerable inter-individual variation. Substantial losses in some individuals appear to associate with disease burden.

Perfusion Quantification of Liver Metastases of Colorectal Cancer Treated with Anti-angiogenic-Based Therapy: Assessment of Intra- and Inter-observer Reproducibility of Parameters in Three Regions of Interest Outlining Lesions.

This study evaluated the reproducibility of dynamic contrast-enhanced ultrasound (DCEUS) parameters outlining liver metastases of colorectal cancer in 45 patients, before and after anti-angiogenic-based therapy. Tumor enhancement was quantified by drawing three regions of interest (ROIs): (i) outlining the tumor based on portal phase DCEUS images, (ii) in the hypo-enhanced center of the lesion and (iii) outlining the lesion using parametric imaging. Perfusion parameters were extracted from time-intensity curves. Another ROI was drawn in healthy liver parenchyma for normalization. Intra- and inter-observer reproducibility of these parameters was evaluated using intra-class correlation coefficients (ICCs). For the three ROIs, both intra- and inter-observer reproducibility were excellent (ICCs ≥0.9) for 50.8% absolute parameters and were moderate to good (0.7 ≤ ICC < 0.9) for 26.7% of them. In healthy liver parenchyma and for normalized parameters, reproducibility was moderate to excellent for 59.4% of intensity parameters and was low (ICC <0.7) for almost all temporal parameters. This study indicates that DCEUS is a reproducible tool for evaluating perfusion parameters.

What is the best salivary gland ultrasonography scoring methods for the diagnosis of primary or secondary Sjögren's syndromes?

OBJECTIVE: To evaluate the performance of salivary gland ultrasonography for the diagnosis of primary and secondary Sjögren's syndromes (pSS and sSS). METHOD: Multicenter cross-sectional study on 97 patients with clinical sicca symptoms. The pSS (n = 22) met the American-European Consensus Group (AECG) classification criteria. The control patients (n = 36) with sicca symptoms did not fulfill the AECG criteria. Four scores were used to evaluate the 4 major salivary gland echostructure: the Salaffi score (0-16), Jousse-Joulin score (0-4), Hocevar score (0-48) and Milic score (0-12). RESULTS: The medians of ultrasonographic (US) scores were higher in the pSS and sSS groups than in the control group (P < 0.001). The receiver-operating characteristic (ROC) curves and the positive likelihood ratio (LR+) of the four scores showed a good diagnostic performance for the US diagnosis of pSS and sSS. Respectively, for pSS and sSS, the AUC were 0.891 (95%CI 0.812-0.970) and 0.824 (95%CI 0.695-0.954) for Hocevar score, 0.885 (95%CI 0.804-0.965) and 0.808 (95%CI 0.673-0.943) for Milic score, 0.915 (95%CI 0.848-0.982) and 0.844 (95%CI 0.724-0.965) for Salaffi score, 0.897 (95%CI 0.821-0.973) and 0.851 (95%CI 0.735-0.968) for Jousse-Joulin score. This study showed an interesting inter-observer reproducibility (kappa = 0.714 ± 0.131) of the US evaluation with 85.7% agreement between reader to determine the pathological character of the salivary glands. CONCLUSION: Salivary gland US is a simple, non-invasive and performant imaging procedure for the diagnosis of pSS and sSS, with Salaffi, Milic and Jousse-Joulin scores.

Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases.

PURPOSE: To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. MATERIALS AND METHODS: This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3 rd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. CONCLUSION: This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC.

Novel use of contrast-enhanced sonography in the diagnosis of central uterine necrosis following embolization for postpartum hemorrhage.

Since 2007, we have identified 2 cases of central uterine necrosis after uterine arterial embolization for postpartum hemorrhage. Contrast-enhanced sonography showed an absence of enhancement of the internal myometrium. Magnetic resonance imaging with gadolinium confirmed the diagnosis. The images obtained for the first case were corroborated by histologic analysis from a hysterectomy done for sepsis. For the second case, contrast-enhanced sonography performed during a follow-up period of conservative treatment revealed a reduction of necrosis. Our study shows that contrast-enhanced sonography seems to be a useful examination as an adjunct to grayscale and power Doppler imaging in the diagnosis and follow-up of uterine necrosis.

Penetration depth with the XPS GreenLight laser assessed by contrast enhanced ultrasonography.

PURPOSE: The GreenLight laser is one of the main alternative treatments for benign prostatic hyperplasia (BPH). Ultrasonography with contrast (ECUS) is one of the main innovations in radiology that has led to the examination of tissue vascularity. The objective of the study was to measure the impact of photovaporization of the prostate (PVP) on the prostate gland with ECUS. PATIENTS AND METHODS: We conducted a pilot study to assess the impact of PVP on the prostate by using ECUS intraoperatively (ethical committee approval No. 2012-001451-39). Twelve patients undergoing PVP for symptomatic BPH were enrolled in this study after providing their informed consent. ECUS was performed just before and after PVP in the operating room and at 1 month postoperatively. RESULTS: Comparative analysis showed that after PVP, a nonvascularized area with an average thickness of 11.1 mm was observed beyond the operative cavity. The nonvascularized area was thinner at 1 month postoperatively and disappeared at 6 months for the six patients evaluated. This is the first study using contrast-enhanced ultrasonography to measure the impact of PVP on the prostate. Our study has the limitations of a pilot study with a small population and a short follow-up. Based on these results, we would advise beginners to take into account the necrosis thickness and to limit the depth of vaporization. CONCLUSIONS: Through the use of ECUS, our study demonstrated that a large area of necrosis is induced around the surgical cavity from the action of the GreenLight laser. Being aware of this phenomenon will certainly reduce the risk of complications induced by surgery.

Non-invasive quantification of tumor vascular architecture during docetaxel-chemotherapy.

New ultrasound parameters, potentially predictive of tumor response to chemotherapy, were sought after analyzing details of vascular architecture of mammary tumors during chemotherapy. Tumor-bearing rats were separated into untreated or docetaxel-treated group (6 mg/kg/week). Power Doppler Index and vascular contrast-enhanced ultrasound (CEUS) reference endpoints (Peak, area under the curve (AUC), blood flow) were evaluated at the beginning (W (0)), and after 2 and 6 weeks of docetaxel treatment (W (+2) and W (+6)). An improved CEUS image analysis, taking advantage of individual pixel intensity, was developed to quantify large, medium, and small vessels of tumors. Standard immunohistochemistry validated this new methodology analyzing tumor vascular architecture. In rats, there was an enrichment of vascularization with large vessels during tumor growth indicative of a vascular adjustment to tumor size. Docetaxel stopped tumor growth, and showed a sequential effect on vascular parameters. After an initial enrichment in larger vessels (by threefold) at W (+2), docetaxel led to a diminution of vascular parameters at W (+6) (-46 % for peak, -55 % for AUC -31 % compared to W (0)) and a vascular remodeling in favor of small vessels. One of the CEUS parameters measured before chemotherapy, the so-called global contrast-enhanced pixels density, was predictive of rat tumor response to treatment (r = 0.80; p < 0.01). The method was then applied in a clinical setting to detect changes of vascular architecture during chemotherapy of human breast carcinoma. The docetaxel chemotherapy of breast carcinomas induced a similar sequential effect, with vessel enlargement after two cycles of docetaxel treatment and an antiangiogenic effect after six cycles. Such vascular remodeling was not noticed when patients were treated with 5-fluorouracil-epirubicin-cyclophosphamide. Taken together, the sharpened analysis of CEUS pixel intensity presented here strengthened the monitoring of breast tumor vasculature with the potential to improve the prediction of docetaxel efficacy.

Preoperative diagnosis of ovarian tumors using pelvic contrast-enhanced sonography.

OBJECTIVE: The purpose of this study was to assess the feasibility of using a contrast agent for the sonographic examination of adnexal tumors and identify discriminating parameters in the preoperative diagnosis of malignant tumors. METHODS: We conducted a prospective descriptive monocenter study that analyzed validated echographic criteria and parameters of the enhancement curve obtained by sonographic contrast agent injection. Patients included were referred for a second opinion after the discovery of a suspicious ovarian image. The final diagnosis was reached after surgery and an anatomopathologic examination. RESULTS: Fifty-two tumors were analyzed. Morphologic and Doppler criteria analyses were conducted as described in the literature. The significant parameters of the enhancement curve were the time-intensity curve total area and the duration of activity of the contrast agent during the first phase of decay (P < .002). The performance of the contrast agent was lower than that of the examiner's subjective diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.78 versus 0.80. When borderline tumors were eliminated, there was an inversion of this, with an AUC of 0.85 versus 0.73. The inclusion of contrast results in the examiner's diagnosis in the context of a bivariate model comparing malignant and borderline tumors with benign tumors provided an AUC of 0.88. CONCLUSIONS: Contrast-enhanced sonography improves preoperative diagnosis of ovarian tumors parameters. The significant parameters of the enhancement curve were significantly different for malignant and benign tumors. Borderline tumors contribute to a reduction of the discriminating capacity of the contrast agent.

Feasability of human endobronchial imaging with a linear-array ultrasound catheter.

PURPOSE: To explore the feasability of imaging lung masses with a novel endobronchial linear-array transducer. METHOD: We used a linear-array transducer of 7 F (2.3 mm in diameter) operating at a center frequency of 10 MHz for endobronchial imaging. We used the probe in 20 subjects with suspected lung cancer to identify and measure the tumor; to asses the tumor's sonographic characteristics, bronchial wall invasion, and presence of lymph nodes; to guide a transbronchial needle aspiration (TBNA); and to evaluate potential side effects. RESULTS: In all patients, the tumor was identified and the relationship with the bronchial wall correctly evaluated through the depiction of a 3-layer wall pattern. Bronchial wall invasion was suspected in 5 patients, small adjacent lymph nodes were detected in 3 patients, and a small pleural effusion was observed close to the lung lesion in 2 patients. The linear-array probe allowed the guidance of successful TBNA with no complications. CONCLUSION: This feasibility study shows that the prototype probe can be used to depict pulmonary lesions and to guide biopsy nodes. Larger series are needed to validate its usefulness in clinical work-ups and patients management.

Role of parametric imaging in contrast-enhanced sonography of hepatic focal nodular hyperplasia.

PURPOSE: To assess the value of parametric imaging during contrast-enhanced sonographic examination in the diagnosis of focal nodular hyperplasia (FNH) of the liver. MATERIALS AND METHODS: Thirty-one patients with solitary FNH underwent contrast-enhanced sonographic examination between January 2003 and June 2004 using SonoVue and a Sequoia scanner equipped with Cadence Contrast Pulse Sequencing software. Contrast enhancement from a time sequence of perfusion frames was estimated using QontraXt software, which provides quantification of perfusion parameters. From the time-intensity curves, we obtained the following parameters: peak enhancement value, Tr (time recovery corresponding to time needed to reach 63% of the peak value), beta parameter corresponding to the exponential factor, and slope corresponding to the slope of the tangent to the arterial phase of enhancement. RESULTS: Among the 4 parameters studied, the slope of the arterial phase of enhancement was the most sensitive to image the centrifugal arterial flow originating from the central portion of the lesion, whereas peak enhancement value and Tr were the most sensitive to image full enhancement of the lesion. A blinded review revealed equivalent sensitivity in the diagnosis of FNH between the interpretation of the original videoclips and that of the parametric images. CONCLUSIONS: The results of this study show that parametric imaging can be used in place of original videoclips for clinical reporting of FNH; furthermore, it could help less-experienced sonologists diagnose FNH.

Adaptive AR and neurofuzzy approaches: access to cerebral particle signatures.

In recent years, a relationship has been suggested between the occurrence of cerebral embolism and stroke. Ultrasound has therefore become essential in the detection of emboli when monitoring cerebral vascular disorders and forms part of ultrasound brain-imaging techniques. Such detection is based on investigating the middle cerebral artery using a TransCranial Doppler (TCD) system, and analyzing the Doppler signal of the embolism. Most of the emboli detected in practical experiments are large emboli because their signatures are easy to recognize in the TCD signal. However, detection of small emboli remains a challenge. Various approaches have been proposed to solve the problem, ranging from the exclusive use of expert human knowledge to automated collection of signal parameters. Many studies have recently been performed using time-frequency distributions and classical parameter modeling for automatic detection of emboli. It has been shown that autoregressive (AR) modeling associated with an abrupt change detection technique is one of the best methods for detection of microemboli. One alternative to this is a technique based on taking expert knowledge into account. This paper aims to unite these two approaches using AR modeling and expert knowledge through a neurofuzzy approach. The originality of this approach lies in combining these two techniques and then proposing a parameter referred to as score ranging from 0 to 1. Unlike classical techniques, this score is not only a measure of confidence of detection but also a tool enabling the final detection of the presence or absence of microemboli to be performed by the practitioner. Finally, this paper provides performance evaluation and comparison with an automated technique, i.e., AR modeling used in vitro.

Differential diagnosis of focal nodular hyperplasia with quantitative parametric analysis in contrast-enhanced sonography.

OBJECTIVES: We investigated the potential of quantitative parametric analysis in the differential diagnosis of focal nodular hyperplasia (FNH) from other hypervascularized liver focal lesions. MATERIALS AND METHODS: Eighty-five focal liver lesions (in 83 patients) were explored using contrast-enhanced ultrasound (SonoVue and Cadence Contrast Pulse Sequencing) consisting of typical FNH (n=52), hepatocellular carcinoma (n=11), hemangioma with high flow (n=8), hypervascular metastases (n=10), and hepatocellular adenoma (n=4). QontraXt software (AMID, Italy) was used here to estimate the following parameters: maximum peak value, Tr (time corresponding to time for obtaining 63% of the plateau), beta parameter corresponding to the exponential factor, and slope corresponding to the tangent value of the first phase of enhancement. These parameters were obtained from the time-intensity curves derived from the enhancement observed in 2 regions of interest corresponding, respectively, to the whole lesion and the central region only. RESULTS: A significant statistical difference (P<0.05) was found in the values of Tr, beta, and slope between FNH and other hypervascularized lesions on both the whole lesion and central region. Among these parameters, slope appeared as the most valuable whatever the region of interest, ie, central or whole lesion (P<0.01). Central region was more accurate in the differentiation of FNH and concordant with visual characterization. CONCLUSION: Quantitative parametric curve analysis of the different hypervascularized lesions confirms the depiction of the central artery in FNH and thus could help in differentiating this specific focal liver lesion from the others.