Long-term survival after adrenalectomy for stage I/II adrenocortical carcinoma (ACC): a retrospective comparative cohort study of laparoscopic versus open approach.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the standard treatment for benign adrenal lesions. The laparoscopic approach has also been increasingly accepted for adrenal metastases but remains controversial for adrenocortical carcinoma (ACC). In a retrospective cohort study we compared the outcome of LA versus open adrenalectomy (OA) in the treatment of stage I and II ACC. METHODS: This was a double cohort study comparing the outcome of patients with stage I/II ACC and a tumor size <10 cm submitted to LA or OA at Lille University Hospital referral center from 1985 to 2011. Main outcomes analyzed were: postoperative morbidity, overall survival, and disease-free survival. RESULTS: Among 111 consecutive patients operated on for ACC, 34 met the inclusion criteria. LA and OA were performed in 13 and 21 patients, respectively. Baseline patient characteristics (gender, age, tumor size, hormonal secretion) were similar between groups. There was no difference in postoperative morbidity, but patients in LA group were discharged earlier (p < 0.02). After a similar follow-up (66 ± 52 for LA and 51 ± 43 months for OA), Kaplan-Meier estimates of disease-specific survival and disease-free survival were identical in both groups (p = 0.65, p = 0.96, respectively). CONCLUSIONS: LA was associated with a shorter length of stay and did not compromise the long-term oncological outcome of patients operated on for stage I/II ACC ≤ 10 cm ACC. Our results suggest that LA can be safely proposed to patients with potentially malignant adrenal lesions smaller than 10 cm and without evidence of extra-adrenal extension.

Reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound.

OBJECTIVES: The aim of this clinical study was to evaluate the reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound. METHODS: Fifteen patients with colorectal liver metastases and 5 volunteers were studied. The hepatic artery proper and the portal vein were imaged simultaneously with dynamic contrast-enhanced ultrasound. The examination was repeated with 2 different contrast bolus volumes (1.2 and 2.4 mL), and time-intensity curves were formed from dynamic contrast-enhanced ultrasound image loops. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Inter-reader, intra-reader, and inter-scan agreement was assessed by 2 independent readers. Quantitative (intraclass correlation coefficients and coefficients of variation [CVs]) and qualitative (Landis and Koch classification) analyses were performed. RESULTS: Intra-reader and inter-reader agreement was "almost perfect" for the hepatic artery (CV, 10%-15% and 8%-9%, respectively), portal vein (CV, 5%-8% and 6%-12%), and hepatic artery/portal vein ratio (CV, 8%-14% and 10%-15%) measurements of 3 all studied parameters. In contrast, inter-scan agreement was only "slight" to "moderate" (CV, 25%-27%) and "fair" to "moderate" (CV, 19%-24%) for rise time and peak intensity measurements in the hepatic artery and portal vein, respectively. CONCLUSIONS: Quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound is reproducible provided that measurements in the hepatic artery are normalized by those in the portal vein.

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials.

Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves.

The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve parameters measurements in a particular clinical scenario of interest, for example that of cancer patients undergoing vascular targeting therapies.

Assessment of global liver blood flow with quantitative dynamic contrast-enhanced ultrasound.

OBJECTIVES: This study assessed the potential of quantitative analysis of contrast bolus kinetics to reflect global liver blood flow. METHODS: A dynamic contrast-enhanced ultrasound flow phantom was developed. A peristaltic pump established constant volume flow ranging between 16.5 and 49.5 mL/min (2-mm tube) and 85.5 and 256.5 mL/min (5-mm tube). After bolus injection of 2 doses of a contrast agent, a region of interest was drawn over the cross section of the tube used for a particular acquisition; the rise time, peak intensity, and wash-in slope were derived from time-intensity curves. Twenty healthy volunteers and 25 patients with biopsy-proven colorectal liver metastases were scanned with dynamic contrast-enhanced ultrasound. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Hepatic artery/portal vein ratios of the parameters were also calculated. RESULTS: In the in vitro experiment, the rise time decreased while the peak intensity and wash-in slope increased with increasing volume flow for both tube diameters and contrast bolus volumes. In the clinical study, the rise time was lowered in the hepatic artery but elevated in the portal vein, and the peak intensity and wash-in slope were elevated in the hepatic artery but lowered in the portal vein in patients with colorectal liver metastases compared with healthy volunteers, although not in a statistically significant manner. This finding was consistent with an increase in hepatic artery blood flow, a decrease in portal vein blood flow, or both in patients with colorectal liver metastases compared with healthy volunteers. Only the 3 hepatic artery/portal vein ratios of the parameters achieved statistical significance in differentiating healthy volunteers from patients with colorectal liver metastases (P < .05). CONCLUSIONS: Surrogate measurements of liver blood flow may be derived from quantitative analysis of dynamic contrast-enhanced ultrasound studies. They may have potential for quick and easy assessment of altered hepatic hemodynamics.

Perfusion quantification using dynamic contrast-enhanced ultrasound: the impact of dynamic range and gain on time-intensity curves.

The objective of this study was to assess the impact of dynamic range and gain on perfusion quantification using linearized log-compressed data. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and a C5-1 curvilinear transducer using a contrast-specific nonlinear pulse sequence (power modulation) at 1.7MHz. Clinical dynamic contrast-enhanced ultrasound image loops of liver tumors were also collected for preliminary validation of the in vitro findings. Time-intensity curves were extracted from image loops with two different approaches: from linearized log-compressed data and from linear (uncompressed) data. The error of time-intensity curve parameters derived from linearized log-compressed data (deviation from linear data) was found to be less than 2.1% and 5.4% for all studied parameters in the in vitro experiment and in the clinical study, respectively, when a high dynamic range setting (at least 50dB on the iU22) is used. The gain must be carefully adjusted to ensure a high signal-to-noise ratio and to avoid signal saturation. From the time-intensity curve analysis it was also found that rise time of the bolus time-intensity curve is the least variable of all the studied time-intensity curve parameters.

Ultrasound-based elastography: a novel approach to assess radio frequency ablation of liver masses performed with expandable ablation probes: a feasibility study.

OBJECTIVE: The purpose of this study was to evaluate the technical feasibility of ultrasound-based elastography as a tool for assessing the size and shape of the coagulation necrosis caused by radio frequency ablation (RFA) probes using expandable electrodes ex vivo as well as in a patient with a liver metastasis. METHODS: A commercially available expandable RFA probe was used to create a 3-cm ablation in a piece of bovine liver. The ablation probe was used in situ to induce tissue deformation for elastography before and after ablation. Ultrasonic radio frequency data were processed to generate elasticity strain images. The appearance of the ablation zone was compared with magnetic resonance imaging and a gross section specimen. One patient with malignant metastatic disease to the liver and a clinical indication for RFA was investigated for the feasibility of percutaneous elastography of RFA using the same technique. Sonographic strain images were compared with the appearance of the nonenhancing ablation zone on contrast-enhanced computed tomography. RESULTS: Ex vivo, the ablation zone on ultrasound-based elastography was represented by an area of increased stiffness and was well demarcated from the nonablated surrounding tissue. The size and shape of the ablated zone on the strain image correlated well with the gross specimen and the magnetic resonance imaging appearance. Strain images obtained from the patient showed results similar to those of the ex vivo experiment and correlated well with the nonenhancing area of ablation on contrast-enhanced computed tomography. CONCLUSIONS: Ultrasound-based elastography may be a promising tool for displaying the ablation zone created by expandable RFA probes.