ICUS Weekly News Monitor 2-16-2017

  1. Dovepress,  Feb 14, 2017,  Correlations of microvascular blood flow of contrast-enhanced ultrasound and HGF/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma    Authors:      Peng-Hui Zhuang, et al
  2. Mass Device,  Feb 2, 2017,  Lantheus wins FDA nod for Definity imaging agent label update. By Fink Densford
  3. StreetInsider.com,  Feb 2, 2017, Lantheus (LNTH) Announces FDA Approval of DEFINITY Label Update
  4. RSNA Radiology,  Feb 1, 2017,  Integration of Contrast-enhanced US into a Multimodality Approach to Imaging of Nodules in a Cirrhotic Liver: How I Do It. Authors: Patricia C. Jo, MD, et al

Dovepress

DOI https://doi.org/10.2147/OTT.S113353

Volume 2017:10 Pages 847—857

Correlations of microvascular blood flow of contrast-enhanced ultrasound and HGF/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma

Feb 14, 2017

Authors: Peng-Hui Zhuang,1 Lei Xu,1 Lu Gao,2 Wei Lu,3 Li-Tao Ruan,4 Jin Yang1

1Department of Surgery, 2Department of Internal Medicine, The Hospital of Xi’an Jiao Tong University, 3Department of Gastroenterology, Xi’an First Hospital, 4Department of Ultrasound, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China

Abstract: The study is designed to explore the correlations of microvascular blood flow of contrast-enhanced ultrasound (CEUS) and hepatocyte growth factor (HGF)/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma (HCC). One hundred and eighteen patients pathologically diagnosed as primary HCC were selected. All HCC patients underwent CEUS examination before operation. HCC tissues and adjacent normal tissue specimens were obtained to detect the protein rates of HGF and c-Met expressions by immunohistochemistry. The mRNA expressions of HGF and c-Met were detected by quantitative real-time polymerase chase reaction assay. The microvessel density (MVD) was tested by CD34 immunohistochemistry. Compared with liver parenchyma, the HCC lesions had higher MVD, preoperative peak intensity (PI), area under the curve (AUC), lower preoperative time to peak (TTP), and washout time (WOT). Compared with adjacent normal tissues, the protein and mRNA expressions of HGF were reduced in HCC tissues, but the protein and mRNA expressions of c-Met and MVD were increased. The protein expressions of HGF and c-Met exhibited evident correlations with TNM stage, tumor size, vascular invasion, liver cirrhosis, and hepatitis B virus and hepatitis C virus infection of HCC patients. The tumor size and number, vascular invasion, the protein expressions of HGF and c-Met, and MVD were associated with the TTP, PI, WOT, and AUC of CEUS in HCC patients. The protein expressions of HGF and c-Met, MVD and preoperative PI revealed negative associations with the prognosis of HCC patients. In conclusion, quantitative parameters of CEUS and HGF/c-Met signaling pathway-related proteins may be helpful for early diagnosis and prognosis prediction of HCC patients.


Mass Device

Lantheus wins FDA nod for Definity imaging agent label update

Feb 2, 2017
By Fink Densford

Lantheus Medical Imaging (NSDQ:LNTH) said today it won FDA approval for a label update on its Definity imaging agent which removed a contraindication related to use in patients with a known or suspected cardiac shunt.

The agent is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and improve the delineation of the left ventricular endocardial border, the North Billerica, Mass.-based company said.

The FDA’s decision to remove the contraindication was based on publications and data supporting the safety of the contrast fluid in patients with cardiac shunts, Lantheus said.

“The echocardiography medical and scientific community has long demonstrated the safety of echocardiographic contrast agents through published clinical studies which has supported the removal of the contraindication for Definity in patients with cardiac shunts. This is particularly noteworthy as Definity is the most widely used echocardiography agent in the U.S. with published data supporting its safety profile across multiple care settings and across gender and race in adults, including those age 65 and older. This is an important step toward broader acceptance and appropriate use of echo contrast agents, which can safely and cost effectively provide critical information to help clinicians accurately diagnose and manage patients to achieve better outcomes,” Dr. Neil Weissman of Washington D.C.’s MedStar Health Research Institute

“The label change implemented by FDA is reflective of both the extensive data on contrast agents and the well characterized and stable safety profile of Definity, which has been used to perform more than seven million echocardiography studies. The removal of the cardiac shunt contraindication is expected to provide patients who could benefit from this important diagnostic tool with greater access to Definity when undergoing cardiac ultrasound imaging,” chief medical officer Cesare Orlandi said in a press release.

Last September, Lantheus priced a $40 million offering with funds slated to pay down approximately $55 million of the outstanding principal balance under its senior secured credit facilities.

In August, Lantheus sold its Australian radiopharmacy servicing business to Global Medical Solutions.


StreetInsider.com

Lantheus (LNTH) Announces FDA Approval of DEFINITY Label Update

Feb 2, 2017

Lantheus Medical Imaging, Inc. (“Lantheus”) today announced U.S. Food and Drug Administration (FDA) approval of an important label update for DEFINITY® Vial for (Perflutren Lipid Microsphere) Injectable Suspension which removes the contraindication statement related to use in patients with a known or suspected cardiac shunt from the U.S. Prescribing Information. DEFINITY is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.

A cardiac shunt is a pattern of blood flow in the heart that deviates from the normal path of the circulatory system, which may present in 10 to 35 percent of patients. These patients were previously excluded from receiving a valuable echo contrast study of the left ventricle. The FDA’s decision to remove the contraindication concerning known or suspected cardiac shunts was based on Lantheus’ submission referencing several publications and data supporting the safety of echocardiography contrast products in patients with cardiac shunts. Information concerning administration in patients with a cardiac shunt appears in the Warnings section of the DEFINITY Prescribing Information.

“The label change implemented by FDA is reflective of both the extensive data on contrast agents and the well characterized and stable safety profile of DEFINITY, which has been used to perform more than seven million echocardiography studies,” said Cesare Orlandi, Chief Medical Officer at Lantheus. “The removal of the cardiac shunt contraindication is expected to provide patients who could benefit from this important diagnostic tool with greater access to DEFINITY when undergoing cardiac ultrasound imaging.”

Neil Weissman, M.D., President of MedStar Health Research Institute (Washington, DC), Professor of Medicine at Georgetown University and Past President of the American Society of Echocardiography commented, “The echocardiography medical and scientific community has long demonstrated the safety of echocardiographic contrast agents through published clinical studies which has supported the removal of the contraindication for DEFINITY in patients with cardiac shunts. This is particularly noteworthy as DEFINITY is the most widely used echocardiography agent in the U.S. with published data supporting its safety profile across multiple care settings and across gender and race in adults, including those age 65 and older.”

Dr. Weissman continued, “This is an important step toward broader acceptance and appropriate use of echo contrast agents, which can safely and cost effectively provide critical information to help clinicians accurately diagnose and manage patients to achieve better outcomes.”


RSNA Radiology

Integration of Contrast-enhanced US into a Multimodality Approach to Imaging of Nodules in a Cirrhotic Liver: How I Do It

Feb 1, 2017
Authors: Patricia C. Jo, MD; Hyun-Jung Jang, MD; Peter N. Burns, PhD; Kelly W. Burak, MD; Tae Kyoung Kim, MD; Stephanie R. Wilson, MD

From the Department of Radiology (P.C.J., S.R.W.) and Department of Medicine, Division of Gastroenterology (K.W.B., S.R.W.), Foothills Medical Centre, University of Calgary, 1403 29 St NW, Calgary, AB, Canada T2N 2T9; Department of Medical Imaging, Toronto General Hospital, University of Toronto, Toronto, Ont, Canada (H.J.J., T.K.K.); and Department of Imaging Research, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (P.N.B.).Address correspondence to S.R.W. (e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. )

DOI: http://dx.doi.org/10.1148/radiol.2016151732

Accurate characterization of cirrhotic nodules and early diagnosis of hepatocellular carcinoma (HCC) are of vital importance. Currently, computed tomography (CT) and magnetic resonance (MR) imaging are standard modalities for the investigation of new nodules found at surveillance ultrasonography (US). This article describes the successful integration of contrast material–enhanced US into a multimodality approach for diagnosis of HCC and its benefits in this population. The application of contrast-enhanced US immediately following surveillance US allows for prompt dynamic contrast-enhanced evaluation, removing the need for further imaging of benign lesions. Contrast-enhanced US also provides dynamic real-time assessment of tumor vascularity so that contrast enhancement can be identified regardless of its timing or duration, allowing for detection of arterial hypervascularity and portal venous washout. The purely intravascular nature of US contrast agents is valuable as the rapid washout of nonhepatocyte malignancies is highly contributory to their differentiation from HCC. The authors believe contrast-enhanced US provides complementary information to CT and MR imaging in the characterization of nodules in high-risk patients.

ICUS Weekly News Monitor 2-9-2017

1.  Mass Device,  Feb 2, 2017,  Lantheus wins FDA nod for Definity imaging agent label update     By Fink Densford
 
2.  StreetInsider.com,  Feb 2, 2017,  Lantheus (LNTH) Announces FDA Approval of DEFINITY Label Update
 
3.  RSNA Radiology,  Feb 1, 2017,  Integration of Contrast-enhanced US into a Multimodality Approach to Imaging of Nodules in a Cirrhotic Liver: How I Do It     Authors: Patricia C. Jo, MD, et al
 
 
_______________________________________
Mass Device
Feb 2, 2017
Lantheus wins FDA nod for Definity imaging agent label update
By Fink Densford
 
Lantheus Medical Imaging (NSDQ:LNTH) said today it won FDA approval for a label update on its Definity imaging agent which removed a contraindication related to use in patients with a known or suspected cardiac shunt.
 
The agent is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and improve the delineation of the left ventricular endocardial border, the North Billerica, Mass.-based company said.
 
The FDA’s decision to remove the contraindication was based on publications and data supporting the safety of the contrast fluid in patients with cardiac shunts, Lantheus said.
 
“The echocardiography medical and scientific community has long demonstrated the safety of echocardiographic contrast agents through published clinical studies which has supported the removal of the contraindication for Definity in patients with cardiac shunts. This is particularly noteworthy as Definity is the most widely used echocardiography agent in the U.S. with published data supporting its safety profile across multiple care settings and across gender and race in adults, including those age 65 and older. This is an important step toward broader acceptance and appropriate use of echo contrast agents, which can safely and cost effectively provide critical information to help clinicians accurately diagnose and manage patients to achieve better outcomes,” Dr. Neil Weissman of Washington D.C.’s MedStar Health Research Institute
 
“The label change implemented by FDA is reflective of both the extensive data on contrast agents and the well characterized and stable safety profile of Definity, which has been used to perform more than seven million echocardiography studies. The removal of the cardiac shunt contraindication is expected to provide patients who could benefit from this important diagnostic tool with greater access to Definity when undergoing cardiac ultrasound imaging,” chief medical officer Cesare Orlandi said in a press release.
 
Last September, Lantheus priced a $40 million offering with funds slated to pay down approximately $55 million of the outstanding principal balance under its senior secured credit facilities.
 
In August, Lantheus sold its Australian radiopharmacy servicing business to Global Medical Solutions.
 
__________________________________
StreetInsider.com
Feb 2, 2017
 
Lantheus (LNTH) Announces FDA Approval of DEFINITY Label Update
 
Lantheus Medical Imaging, Inc. (“Lantheus”) today announced U.S. Food and Drug Administration (FDA) approval of an important label update for DEFINITY® Vial for (Perflutren Lipid Microsphere) Injectable Suspension which removes the contraindication statement related to use in patients with a known or suspected cardiac shunt from the U.S. Prescribing Information. DEFINITY is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.
 
A cardiac shunt is a pattern of blood flow in the heart that deviates from the normal path of the circulatory system, which may present in 10 to 35 percent of patients. These patients were previously excluded from receiving a valuable echo contrast study of the left ventricle. The FDA’s decision to remove the contraindication concerning known or suspected cardiac shunts was based on Lantheus’ submission referencing several publications and data supporting the safety of echocardiography contrast products in patients with cardiac shunts. Information concerning administration in patients with a cardiac shunt appears in the Warnings section of the DEFINITY Prescribing Information.
 
“The label change implemented by FDA is reflective of both the extensive data on contrast agents and the well characterized and stable safety profile of DEFINITY, which has been used to perform more than seven million echocardiography studies,” said Cesare Orlandi, Chief Medical Officer at Lantheus. “The removal of the cardiac shunt contraindication is expected to provide patients who could benefit from this important diagnostic tool with greater access to DEFINITY when undergoing cardiac ultrasound imaging.”
 
Neil Weissman, M.D., President of MedStar Health Research Institute (Washington, DC), Professor of Medicine at Georgetown University and Past President of the American Society of Echocardiography commented, “The echocardiography medical and scientific community has long demonstrated the safety of echocardiographic contrast agents through published clinical studies which has supported the removal of the contraindication for DEFINITY in patients with cardiac shunts. This is particularly noteworthy as DEFINITY is the most widely used echocardiography agent in the U.S. with published data supporting its safety profile across multiple care settings and across gender and race in adults, including those age 65 and older.”
 
Dr. Weissman continued, “This is an important step toward broader acceptance and appropriate use of echo contrast agents, which can safely and cost effectively provide critical information to help clinicians accurately diagnose and manage patients to achieve better outcomes.”
 
_______________________________
RSNA
Radiology
DOI: http://dx.doi.org/10.1148/radiol.2016151732
Feb 1, 2017
 
Integration of Contrast-enhanced US into a Multimodality Approach to Imaging of Nodules in a Cirrhotic Liver: How I Do It
Authors: Patricia C. Jo, MD; Hyun-Jung Jang, MD; Peter N. Burns, PhD; Kelly W. Burak, MD; Tae Kyoung Kim, MD; Stephanie R. Wilson, MD
 
From the Department of Radiology (P.C.J., S.R.W.) and Department of Medicine, Division of Gastroenterology (K.W.B., S.R.W.), Foothills Medical Centre, University of Calgary, 1403 29 St NW, Calgary, AB, Canada T2N 2T9; Department of Medical Imaging, Toronto General Hospital, University of Toronto, Toronto, Ont, Canada (H.J.J., T.K.K.); and Department of Imaging Research, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ont, Canada (P.N.B.).Address correspondence to S.R.W. (e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ).
 
Abstract
Accurate characterization of cirrhotic nodules and early diagnosis of hepatocellular carcinoma (HCC) are of vital importance. Currently, computed tomography (CT) and magnetic resonance (MR) imaging are standard modalities for the investigation of new nodules found at surveillance ultrasonography (US). This article describes the successful integration of contrast material–enhanced US into a multimodality approach for diagnosis of HCC and its benefits in this population. The application of contrast-enhanced US immediately following surveillance US allows for prompt dynamic contrast-enhanced evaluation, removing the need for further imaging of benign lesions. Contrast-enhanced US also provides dynamic real-time assessment of tumor vascularity so that contrast enhancement can be identified regardless of its timing or duration, allowing for detection of arterial hypervascularity and portal venous washout. The purely intravascular nature of US contrast agents is valuable as the rapid washout of nonhepatocyte malignancies is highly contributory to their differentiation from HCC. The authors believe contrast-enhanced US provides complementary information to CT and MR imaging in the characterization of nodules in high-risk patients.

ICUS Weekly News Monitor 2-2-2017

1.  Diagnostic Imaging,  Feb 1, 2017,  Contrast-enhanced Ultrasound in Children
 
2.  American Journal of Roentgenology,  Feb, 1, 2017,  Retrospective Analysis of the Safety and Cost Implications of Pediatric Contrast-Enhanced Ultrasound at a Single Center     Authors: Gibran T. Yusuf, et al
 
3.  Medscape - Heartwire,  Jan 12, 2017,  FDA Removes Shunt Contraindication From Lumason Label     By Larry Hand
 
4.  Central European Journal of Urology,  Nov 30, 2016,  Contrast enhanced ultrasound in urothelial carcinoma of urinary bladder: An underutilized staging and grading modality.     Authors:  Gupta VG, et al
 
________________________________
Diagnostic Imaging
Feb 1, 2017
 
Contrast-enhanced Ultrasound in Children
 
Pediatric contrast-enhanced ultrasound (CEUS) is a safe procedure and allows for less ionizing radiation and gadolinium contrast administration, according to a study in the American Journal of Roentgenology.
 
Researchers from the United Kingdom analyzed adverse incidents encountered in pediatric CEUS, and sought to determine if there were financial benefits to reducing the number of CT and MRI examinations among children.
 
The researchers analyzed all CEUS examinations performed on children aged 18 and younger between January 2008 and December 2015. The children received a median dose of 2.4 mL of a sulfur hexafluoride microbubble contrast agent, with ranges from 0.1 mL to 4.8 mL. All immediate reactions deemed due to contrast examinations were documented in radiology reports. Electronic patient records were examined for adverse reactions within 24 hours not due to an underlying pathologic condition. Costs were also compared: CEUS utilization cost at $94, CT at $168, and MRI at $274.
 
The results showed that of 187 boys and 118 girls (305 children total), 147 studies (48.2%) were ordered to characterize liver lesions and 113 studies (37.1%) for trauma. The remaining 45 studies (14.8%) were for renal, vascular, and intracavitary assessment. There were no immediate adverse reactions and delayed adverse reactions occurred in two patients (0.7%): transient hypertension and transient tachycardia. Neither was symptomatic, and both were deemed not due to the underlying disorder. The potential cost savings of CEUS was $74 per examination over CT and $180 over MRI.
 
The researchers concluded that the use of pediatric CEUS is safe and potentially cost-effective. Using CEUS in this population allows reduction in the ionizing radiation associated with CT and in the gadolinium contrast administration, sedation, and anesthesia sometimes required for MRI.
 
_________________________________
American Journal of Roentgenology
Volume 208, Number 2
Feb, 1, 2017
 
Retrospective Analysis of the Safety and Cost Implications of Pediatric Contrast-Enhanced Ultrasound at a Single Center
Authors: Gibran T. Yusuf1, Maria E. Sellars1, Annamaria Deganello1, David O. Cosgrove1 and Paul S. Sidhu1
 
Affiliation: 1Department of Radiology, King's College London, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
Citation: American Journal of Roentgenology. 2017;208: 446-452. 10.2214/AJR.16.16700
 
ABSTRACT :
OBJECTIVE. Because of concern over medical ionizing radiation exposure of children, contrast-enhanced ultrasound (CEUS) has generated interest as an inexpensive, ionizing radiation–free alternative to CT and MRI. CEUS has received approval for pediatric hepatic use but remains off-label for a range of other applications. The purposes of this study were to retrospectively analyze adverse incidents encountered in pediatric CEUS and to assess the financial benefits of reducing the number of CT and MRI examinations performed.
 
MATERIALS AND METHODS. All pediatric (patients 18 years and younger) CEUS examinations performed between January 2008 and December 2015 were reviewed. All immediate reactions deemed due to contrast examinations were documented in radiology reports. Electronic patient records were examined for adverse reactions within 24 hours not due to an underlying pathologic condition. With tariffs from the U.K. National Institute of Clinical Excellence analysis, CEUS utilization cost ($94) was compared with the CT ($168) and MRI ($274) costs of the conventional imaging pathway.
 
RESULTS. The records of 305 pediatric patients (187 boys, 118 girls; age range, 1 month–18 years) undergoing CEUS were reviewed. Most of the studies were for characterizing liver lesions (147/305 [48.2%]) and trauma (113/305 [37.1%]); the others were for renal, vascular, and intracavitary assessment (45/305 [14.8%]). No immediate adverse reactions occurred. Delayed adverse reactions occurred in two patients (2/305 [0.7%]). These reactions were transient hypertension and transient tachycardia. Neither was symptomatic, and both were deemed not due to the underlying disorder. The potential cost savings of CEUS were $74 per examination over CT and $180 over MRI.
 
CONCLUSION. Pediatric CEUS is a safe and potentially cost-effective imaging modality. Using it allows reduction in the ionizing radiation associated with CT and in the gadolinium contrast administration, sedation, and anesthesia sometimes required for MRI.
 
Read More: http://www.ajronline.org/doi/abs/10.2214/AJR.16.16700
 
_________________________________
Medscape - Heartwire
January 12, 2017
 
FDA Removes Shunt Contraindication From Lumason Label
By Larry Hand
 
Bracco Diagnostics has announced that the Food and Drug Administration has removed from the label of Lumason the contraindication that it should not be used in patients with known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts.
 
The FDA posted the new label for Lumason (sulfur hexafluoride lipid-type A microspheres) on its website December 22, 2016.
 
The new label maintains a specific warning that some intravenously injected microspheres could bypass the filtering by the lung and enter the arterial circulation and that Lumason should not be administered by intra-arterial injection.
 
"The removal of this contraindication implies that the FDA has determined that the benefits from the diagnostic information that could be obtained through the use of Lumason in patients with cardiac shunts may outweigh the risk for systemic embolization," Dr Alberto Spinazzi (Global Medical and Regulatory Affairs, Bracco Group) stated in the release.
 
Lumason, an ultrasound contrast agent made up of gas-filled microspheres to enhance echogenicity of blood or urine, was initially approved by the FDA in 2014 for use in adults with suboptimal echocardiograms. Known globally as Sonavue, it gained additional approval in 2016 for use in ultrasonography of the liver in adult and pediatric patients and for use in the evaluation of suspected or known vesicoureteral reflux in pediatric patients.
 
The Centers for Medicare and Medicaid Services granted "pass-through" status in 2015 for reimbursement of Lumason in liver or abdominal ultrasound with contrast.
 
__________________________________
Central European Journal of Urology
Cent European J Urol. 2016;69(4):360-365.
doi: 10.5173/ceju.2016.893. Epub 2016 Nov 30
Nov 30, 2017.
 
Contrast enhanced ultrasound in urothelial carcinoma of urinary bladder: An underutilized staging and grading modality.
Authors:  Gupta VG1, Kumar S2, Singh SK1, Lal A3, Kakkar N4.
 
1Post Graduate Institute of Medical Education and Research, Chandigarh, India.
2Department of Urology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
3Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
4Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
 
Abstract
 
INTRODUCTION:
To evaluate contrast enhanced ultrasound (CEUS) as a modality to predict T stage of cancer of urinary bladder (CAUB) and to predict the grade of the tumor preoperatively.
MATERIAL AND METHODS:
110 patients with CAUB presenting to the Department of Urology at our institution between July 2014 and December 2015 underwent CEUS prior to endoscopic resection and the CEUS findings were compared with histopathology results.
RESULTS:
CEUS had a sensitivity of 75, 65 and 90% and specificity of 95, 85 and 92% in detecting Ta, T1 and muscle invasion respectively. CEUS had a sensitivity of 78% and specificity of 85% in detecting the grade of the lesion.
CONCLUSIONS:
CEUS is a good alternative for T staging and grading of CAUB preoperatively. It is uniquely advantageous in detecting clots or necrosis and in patients with low eGFR where other imaging modalities are contraindicated.

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