Ultrasound Detects Abdominal Cancers without Radiation

Contrast Enhanced Ultrasound (CEUS) Detects Abdominal Cancers without Radiation

Abdominal cancers may be detected sooner, with more specificity, and without exposing patients to ionizing radiation using a simple "contrast-enhanced ultrasound" (CEUS) scan, according to preliminary results of a new Canadian study.

"This readily available ultrasound tool can replace some CT scans, allowing us to accurately diagnose these cancers without radiation and at a significantly lower cost," said Dr. Stephanie Wilson, Professor of Radiology at the University of Calgary and a practicing radiologist at Foothills Medical Center in Calgary.

By comparison, expensive "big box" imaging tools like CT, PET and SPECT (nuclear) imaging all expose patients to ionizing radiation, which can increase an individual's lifetime risk of cancer, according to Wilson.

One patient in the Canadian study was a 42-year-old man with acute flank pain and a high creatinine, according to Wilson. The patient could not tolerate a CT contrast agent, and a non-enhanced CT showed a mass suggesting a spontaneous retroperitoneal hematoma. A subsequent CEUS scan showed aggressive infiltrative kidney cancer. "He should have had CEUS from the beginning," Wilson said.

Another patient was a 32-year-old man who had pain after jogging. CEUS found a mass in his bladder and allowed physicians to characterize it as transitional cell carcinoma, which was missed on an earlier non-enhanced CT scan performed under a protocol specifically aimed at finding stones in the kidneys, ureters or bladder. "Fortunately, because of CEUS, this young man's cancer was promptly treated," Wilson said.

Wilson said that CEUS is an "excellent tool" for detecting cancers of the kidney, liver, bladder, spleen, bowel and gall bladder, and for helping physicians differentiate between malignant and benign tumors.

CEUS uses a special ultrasound contrast agent to improve the clarity and accuracy of a standard ultrasound image. The ultrasound contrast agent is injected into the patient's arm vein during the ultrasound exam and is metabolized and expelled from the body within minutes, according to Wilson. No ionizing radiation is used in standard ultrasound or CEUS, and ultrasound contrast agents do not contain the type of dye that can damage kidneys or other organs, she said.

CT scans generally are performed with the use of intravenously-injected CT contrast agents -- substances that, unlike ultrasound contrast agents, may damage kidneys. Therefore, in patients with compromised kidney function or prior allergy, CT scans are performed "dry" -- that is, without the benefit of these agents.

"This produces an inferior CT scan that does not detect many tumors, especially those that may be growing in the abdominal solid organs such as the kidney or liver," according to Wilson. "And if a non-enhanced CT scan does detect a tumor, it will not permit a definitive diagnosis. For this reason, CEUS may make a significant contribution to patient management."

Wilson said her team compared CEUS to non-enhanced CT because many patients cannot tolerate CT contrast agents. However, she said that based on her experience, CEUS also may be superior to contrast-enhanced CT because of CEUS' diagnostic accuracy, lack of ionizing radiation, and significantly lower cost.

According to preliminary results of the study, based on results in 117 patients to date:

-- In 72 patients with liver masses, CEUS allowed physicians to confidently identify and characterize all of the masses while non-enhanced CT missed part or all of the mass (32), or failed to allow physicians to confidently characterize the mass (40).

-- In 35 patients with kidney masses, CEUS showed the masses to be either vascular or avascular (indicating the presence of cancer). Non-enhanced CT showed 30 of those masses but did not permit confident characterization of any of them.

-- CT was marginally superior in imaging the retroperitoneum and was superior in the bones, where ultrasound is not useful.

Wilson recommended CEUS as an alternative to non-enhanced CT unless the patient has a high likelihood of bone disease or retroperitoneal disease.

According to Wilson, "CEUS may be an ideal imaging tool that can provide a safe and cost-effective alternative to CT, MRI, PET and SPECT (nuclear) scans. While these imaging tools are sometimes useful, CEUS is much less expensive and often provides equivalent if not superior diagnostic accuracy without any ionizing radiation whatsoever, and without risk of damaging kidneys or other organ systems."

CEUS imaging is FDA-approved in the United States for certain types of cardiac imaging, but CEUS is approved and routinely used in Europe, Canada, Asia and Brazil for pinpointing disease and tumors in other parts of the body as well. Ultrasound contrast agents may be used for unapproved indications with patient consent, according to Wilson.

"Since ultrasound contrast agents circulate throughout the bloodstream, you can really image almost any part of the body -- depending on where you place the transducer," said Dr. Steven Feinstein, a cardiologist at Rush University Medical Center in Chicago. Feinstein is director of the annual CEUS conference in Chicago and is Co-president of the International Contrast Ultrasound Society (ICUS), the only international and inter-disciplinary medical society exclusively devoted to CEUS imaging. ICUS has members in 58 countries, including cardiologists, radiologists, gastroenterologists, vascular medicine specialists, and other medical imaging professionals and scientists.

Feinstein uses CEUS to evaluate heart disease and, with patient consent, to detect plaque in neck arteries that may place patients at risk of stroke.

"The United States is actually behind the rest of the world when it comes to using CEUS," said Dr. Barry Goldberg, Co-president of ICUS and director of the Division of Diagnostic Ultrasound at Thomas Jefferson University Hospital in Philadelphia. Goldberg also is past president of national and international radiology societies.

"CEUS is cheaper, better, safer, and can avoid riskier and more expensive downstream tests," said Feinstein. "Also, since ultrasound equipment can be moved to the patient, CEUS offers immediate, real time diagnoses right at the bedside, which can be crucial when caring for critically ill patients who cannot be moved to an MRI or CT machine and cannot wait for a diagnosis."

"Contrast-enhanced ultrasound is clearly a bargain compared to CT and MRI," said Wilson, who said that the cost impact of imaging procedures has "never been more important than it is today."

Nevertheless, according to Wilson, "reimbursement of CEUS is not yet competitive with CT and MRI, so the financial incentives have not caught up with all of the science that now shows very clearly the incredible benefits to patients and the safety of this very important diagnostic tool."

Earlier work by Wilson showed that CEUS can be useful in assessing chronic gastro-intestinal disorders such as inflammatory bowel disease (IBD), which often afflicts young people and can require monitoring throughout life. CEUS may avoid the need for repeat CT scans, thereby reducing exposure to ionizing radiation over these young patients' lifetimes.

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Article written by staff at marketwatch.com and adapted for the purposes of this newsletter.

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Ultrasound Allows Early Ovarian Cancer Diagnosis

Ovarian cancer screening with transvaginal ultrasound has shifted the balance of detection to early-stage disease and improved survival, according to a study reported here.
Early-stage tumors have accounted for about 70% of cancers diagnosed through the Kentucky-based program. Patients with screen-detected ovarian cancer had an estimated five-year survival of 88%, as compared with 40% to 50% for unscreened patients in two different cancer registries.

Diagnostic accuracy has improved with the integration of an imaging-based morphology index for assessing tumor growth potential, Edward J. Pavlik, MD, reported.

"Approximately two thirds of ovarian abnormalities on transvaginal ultrasound will resolve on their own, so that many abnormalities discovered by transvaginal ultrasound can be subjected to short-term surveillance as an alternative to surgery, which improves the positive predictive value of screening," said Pavlik, of the University of Kentucky in Lexington.

"Importantly, overall screening expenses are in balance with savings from preventing advanced disease."

The findings contrast sharply with those reported earlier this year from the NIH-sponsored Prostate, Lung, Colon, and Ovary (PLCO) screening program. Women screened with transvaginal ultrasound and CA125 antigen testing had ovarian cancer survival similar to that of unscreened women in the general population (JAMA. 2011; 305: 2295-2303).

The PLCO report also showed that about 70% of screen-detected cancers were advanced stage at diagnosis, said Pavlik.

Pavlik presented data from a statewide ovarian cancer screening program coordinated by the University of Kentucky. Since 1987 more than 37,000 women have undergone 203,000 transvaginal ultrasound screening studies. During that time, 72 cancers have been detected.

The overall performance of screening with transvaginal ultrasound consisted of sensitivity of 85.7%, specificity of 98.8%, positive predictive value of 13.7%, negative predictive value of 99.97%, and accuracy of 98.8%.

Recently, the group has focused on strategies to improve the positive predictive value of the screening program. The PPV improved by 50% (13.7% to 20.2%) after investigators found they could safely follow simple and septated cysts without surgery. Other performance parameters either improved slightly or stayed the same.

Additional performance improvement has come from use of a lesion morphology index developed by the group in the 1990s. The 10-point index takes into account tumor volume and structure.

By combining the index with serial transvaginal ultrasound studies, investigators have found that they can identify complex ovarian structures that eventually will resolve without intervention. Experience in the screening program has shown that two thirds of the suspicious structures resolve uneventfully.

After accounting for the high proportion of resolution without intervention, the PPV has increased to 24.2% over the past three years, a 77% improvement over the initial performance.

"Essentially, the 72 malignancies have been corrected to 54 early-stage ovarian cancer detections," said Pavlik.

Applying the findings to a cost analysis, the investigators have found that the savings from preventing advanced disease balance the expense of screening.

Assuming a cost of $92,100 for treating stage IIIc ovarian cancer, the 54 cancers would have resulted in $4,973,400 in expenditures had they progressed to advanced stage. The savings would cover the cost of 165,780 transvaginal ultrasound tests (assuming $30 per screen).

"After adjusting for the substantial reduction in surgical expenses related to improved positive predictive value, the net result would approach balancing the overall cost of screening," said Pavlik.

The reasons for the contradictory results of the Kentucky and PLCO studies are unclear, but Pavlik suggested two possible factors that have helped the Kentucky screening program.

"We've found that women talk to each other," he said tongue-in-cheek during an interview. "Word of the screening program has spread without our having to promote it. Women come to us because they have heard about it from other women. A second possible factor is better access to the healthcare services."

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Article written by staff at medpagetoday.com and adapted for the purposes of this newsletter.

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Should Ultrasound Guide Therapy in Juvenile Idiopathic Arthritis ?

Should children whose juvenile idiopathic arthritis has been diagnosed by ultrasound be treated as aggressively as those whose disease is diagnosed clinically?

Researchers presenting last week at the Pediatric Rheumatology European Society Congress in Bruges, Belgium, offered both cautious and enthusiastic perspectives on musculoskeletal ultrasound, the use of which has become ubiquitous in pediatric rheumatology.

Dr. Silvia Magni-Manzoni, of Fondazione San Matteo in Pavia, Italy, presented results from a recent Europe-wide survey that showed that ultrasound is now being used by more than 90% of pediatric rheumatologists in their practices, with 40% of them using the technology personally according to Dr. Magni-Manzoni, who conducted the survey with her associates.

Their 10-question survey of nearly 400 pediatric rheumatologists achieved a 24% response rate, with answers from 37 countries. The investigators collected information about current use in daily practice, the clinical relevance of ultrasound, and areas for prospective development. Nearly three-quarters of respondents said that ultrasound allowed for the immediate improving of diagnosis of joint and soft tissue disease, and 70% said they considered ultrasound important for diagnosis, therapy monitoring, and research.

However, Dr. Magni-Manzoni further cautioned about using ultrasound to predict the course of disease and make treatment recommendations in juvenile idiopathic arthritis (JIA).

Ultrasound diagnoses have led to the reclassification of JIA patients' disease subtypes; for example, patients considered by clinical exam to be oligoarthritic have been reclassified as polyarthritic after ultrasound. "Clinical and ultrasound examinations show different sensitivity in detecting synovitis, especially for peripheral joints," she noted.

Last fall, Dr. Magni-Manzoni presented findings at the annual meeting of the American College of Rheumatology that showed how pronounced the discrepancy between clinical and ultrasound-detected synovitis can be. Looking at 28 consecutive JIA patients determined by clinical exam to be in remission, Dr. Magni-Manzoni and colleagues found synovial hyperplasia in 75% of these patients following immediate referral for ultrasound examination.

But the decision to treat earlier or more aggressively in patients with ultrasound-detected symptoms depends on whether the ultrasound-detected synovitis, joint diffusion, or synovial hyperplasia will ultimately translate into disease flares, she said.

Dr. Magni-Manzoni said that her team has been exploring the question, following 39 consecutive JIA patients who had been diagnosed at baseline with clinically inactive disease, but after a separate ultrasound exam immediately afterward were found to have subclinical symptoms.

After 2 years' follow up, Dr. Magni-Manzoni and colleagues found that subclinical, ultrasound-detected synovial symptoms were not predictive of disease flares. More than 60% of the study subjects still had clinically inactive disease, even though three-quarters of them had ultrasound-detected synovial hyperplasia, and two-thirds had joint diffusion, at baseline.

In a separate presentation in at the pediatric rheumatology congress, Dr. Athimalaipet V. Ramanan discussed his data showing that ultrasound can be used successfully in specific applications in JIA. Used as a visual guide, ultrasound can produce accurate and effective temporomandibular joint injections as evidenced from a small study (n = 39).

The study involved children with JIA that was complicated by temporomandibular joint (TMJ) involvement. TMJ arthritis symptoms resolved in 92% of children within 2 months after ultrasound-guided corticosteroid injection. However, Dr. Ramanan, of the Bristol Royal Hospital for Children in Bristol, U.K., also noted his group had not found ultrasound helpful in diagnosis (Pediatric Rheumatology).

Noting that data presented by other investigators at the congress showed that blind TMJ injections in children with JIA were as successful as ones that were guided radiologically, Dr. Ramanan told the congress that despite lingering uncertainties, "We think the possibility of problems will be a lot lower with guided rather than blind injections."

Dr. Magni-Manzoni told the congress that she agreed that ultrasound-guided joint injections, such as those investigated by Dr. Ramanan and colleagues, were "very useful" in clinical practice. She expressed the need for more guidelines and for better knowledge of ultrasound anatomy in healthy children as reference. "Ultrasound reference values are not known in healthy children," she said.

While ultrasound has considerable advantages for the pediatric rheumatologist, Dr. Magni-Manzoni said, "There are some challenges." Ultrasound is not sensitive in helping identify disease in all joints, such as TMJ, she pointed out; the quality of imaging depends on the type of machine used and the operator's technique; and operators require constant practice.