September 3, 2010

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Endoscopic Ultrasound at Abington Advances Diagnostic Precision

Atherosclerosis Starts Early in Rheumatoid Arthritis (RA)

Ultra Small Transducers Could Bring Ultrasound to the Cellular Level

Subharmonic Breast Ultrasound Technique Shows Promise

Endoscopic Ultrasound at Abington Advances Diagnostic PrecisionEndoscopic ultrasonography, or EUS, provides an important bridge between a suspected diagnosis and appropriate therapy. The procedure uses a thin, flexible endoscope containing a tiny ultrasound probe to examine the upper and lower gastrointestinal tract as well as nearby organs such as the pancreas, gall bladder and liver.

EUS enables gastroenterologists specially trained in its use to identify, evaluate and stage a wide range of benign and malignant conditions. Although its therapeutic applications have been expanding recently, EUS still might best be described as an intermediary diagnostic procedure that provides accurate diagnoses that can lead to the appropriate endoscopic, surgical or medical treatments.

Those capabilities have advanced dramatically since endoscopic ultrasound first was  developed to evaluate the difficult-to-examine pancreas. Today, through EUS, patients are able to be assessed for bile duct blockages, chronic pancreatitis, staging of esophageal, stomach or rectal cancers, enlarged lymph nodes in the chest or abdomen, pancreatic cysts, submucosal gastrointestinal lesions, bile duct stones and more.

At Abington Memorial Hospital, one of the few non-academic centers in the region with EUS services, patients are referred for the procedure due to both presenting symptoms, such as unexplained abdominal pain or jaundice, and disorders that are detected only incidentally during other tests.

For example, we recently saw a patient who had undergone magnetic resonance imaging (MRI) for back problems. That test had incidentally noticed a one-centimeter pancreatic cyst. Such incidental findings are happening more and more frequently as computed tomography (CT) and MRI technologies improve.

When I examined the cyst with EUS, I discovered a nodule within it. Since endoscopic ultrasound also enables me to do fine-needle aspiration, we were able to determine that the nodule was pre-cancerous or cancerous based on cytology. This condition was detected in a patient who had no pancreatic cancer symptoms and only a very small lesion (less than half-an-inch). Because EUS identified that the nodule was suspicious for malignancy, the patient could have it surgically removed instead of having a deadly lesion grow silently over the next few years until it might be too late for surgery.

This is not an isolated example. At one time, pancreatic cysts were thought to be only the result of previous attacks of pancreatitis. Advanced technology now is showing us many instances in which patients have such cysts without having had pancreatitis. Currently, about 30 to 40 percent of the EUS patients I see—the largest patient category in my experience—are being evaluated for pancreatic cystic lesions, many of which are discovered incidentally.

EUS also provides excellent differentiation of the characteristics of submucosal lesions throughout the gastrointestinal tract. Patients being evaluated for these lesions comprise my second-largest EUS patient category. By investigating with EUS, we can determine which layer of the intestinal wall a lesion is arising from as well as its imaging characteristics.

We are also able to sample it through fine-needle aspiration or core biopsy. Through this evaluation, we are often able to determine the character of the lesion and whether it can be watched or needs to be removed. The types of submucosal lesions commonly seen are lipomas, leiomyomas, carcinoid tumors and gastrointestinal stromal tumors.

Endoscopic ultrasound has proven to be a highly accurate adjunct for local and regional tumor staging in addition to CT or positron emission tomography (PET) scans. With EUS, we are able to pick up cancer spread to even very small lymph nodes—spread that may not be detected on CT or PET—and sample nodes for malignancy. By avoiding under-staging, we may spare the patient having to undergo a treatment that would not have brought any benefit.

As a therapeutic endoscopist, I use EUS and endoscopic retrograde pancreatography (ECRP) for therapeutic procedures including the placement of stents to drain blocked bile ducts and the extraction of bile duct stones or sludge. EUS is a less-invasive procedure that can help guide the treatment of patients with disorders of the bile ducts and pancreas. EUS may also be used to drain pancreatic pseudocysts that are symptomatic or not resolving on their own.

It can also be used to help manage pain that has not responded well to medication by injecting medication adjacent to the celiac plexus, a group of nerves that supplies sensation to the pancreas and other abdominal organs. This medication can be delivered as a celiac plexus block (temporary) in patients with non-malignant pain or as a neurolysis (permanent) in patients with cancer-related pain.

The only patient preparation needed for EUS is fasting after midnight, although rectal EUS usually requires enema to clean out the lower colon. Patients on blood thinners, aspirin or non-steroidal anti-inflammatory medications should discontinue such use for a week beforehand, to minimize the risk of bleeding if fine-needle aspiration is used. For aspirating a cyst, patients may receive an antibiotic before and after the procedure.

Endoscopic ultrasound is very safe, with risks similar to routine endoscopy. EUS procedures take longer than routine endoscopy—an upper EUS might last 60 to 75 minutes, compared with 10 to 15 minutes for the routine version—so prolonged sedation is an issue. An anesthesiologist usually manages the sedation. In the more than 550 EUS procedures I’ve performed, there have been very few complications.

With more than half of our EUS cases related to cancer evaluation, we know that patients may be anxious going into these procedures. We would always like to give them good news after EUS. When that isn’t possible, we are usually able to give them some hope, through accurate staging that gets them to the correct therapy they need as quickly as possible.

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

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Atherosclerosis Starts Early in Rheumatoid Arthritis (RA)

The atherosclerotic process begins very early in the course of rheumatoid arthritis (RA), an ongoing prospective Swedish study has found.

Only 18 months after diagnosis, intima-media thickness -- an overall indicator of atherosclerosis -- had increased significantly from 0.52 mm to 0.57 mm (P<0.05) among patients but not among matched controls, according to Anna Södergren, MD, of University Hospital in Umeå, and colleagues.

The increase was significant even though all the patients were being treated with disease-modifying anti-rheumatic drugs and had low levels of inflammation, the researchers wrote online in Arthritis Research & Therapy.

Södergren's group has previously shown that patients with longstanding RA have premature atherosclerosis and endothelial dysfunction. To explore the hypothesis that atherosclerotic changes might be present in early RA, they enrolled 79 patients from northern Sweden who were younger than 60 at the time of diagnosis, along with 44 age- and sex-matched controls.

Clinical examinations found that RA patients had significantly higher systolic blood pressure, elevated triglycerides, and more years of smoking compared with controls (P<0.05 for all).

The investigators performed baseline ultrasound examinations to measure intima-media thickness and to look for signs of endothelial dysfunction such as impaired flow-mediated vascular dilation of the peripheral arteries.

They found no differences on these ultrasound measurements between cases and controls, however. There also was no relationship between baseline ultrasound measurements and disease activity measures including disease activity score in 28 joints (DAS28), erythrocyte sedimentation rate, and C-reactive protein.

But when they measured a number of biomarkers of inflammation, hemostasis, and endothelial function that have been linked to atherosclerosis, they found significantly higher baseline levels of:

• Soluble intercellular adhesion molecule (sICAM)-1, 354.1 versus 290.6 ng/mL,P<0.05
• Monocyte chemotactic protein (MCP)-1, 1,945.6 versus 1,125.1 pg/L, P<0.001
• Von Willebrand factor (vWF), 203.1% versus 161.8%, P<0.05

These differences remained significant after adjustment for age, sex, systolic blood pressure, smoking history, and lipids. A subgroup of 27 patients and their controls had repeat ultrasound evaluations at 18 months, and unlike the RA patients, significant changes were not seen for intima-media thickness in the controls.

Endothelium-dependent vasodilation at 18 months had not changed significantly in either cases or controls, indicating that although endothelial activation was present, it had not yet progressed to endothelial dysfunction.

The investigators then performed regression analyses, finding that decreased levels of soluble (s)L-selectin, an adhesion molecule which is downregulated in chronic inflammation, were inversely related to patients' DAS28 score (which measures inflammation).

And in multiple linear regression models after adjusting for inflammation, a significant association remained for sL-selectin and endothelial dysfunction. "This implies a durable relationship between sL-selectin and endothelial function in early RA, a relation that seems not to be mediated simply via inflammatory disease activity. This is a new finding that warrants further investigation of pathophysiologic mechanisms beyond the inflammatory pathway," the investigators observed They also determined that chemoattractant MCP-1, secreted by activated endothelial cells, was an independent predictor of intima-media thickness.

This protein promotes plaque growth, and in these patients was associated with tissue plasminogen activator (tPA) mass, a hemostatic factor also produced by the endothelium. The study findings suggest that sL-selectin is a strong predictor of the earliest endothelial activation, while increases in MCP-1 reflect a later phase of early atherosclerosis, according to the investigators.

"Taken together, our results point towards an ongoing endothelial activation among patients with early RA," they wrote. These findings also highlight the importance of prevention and treatment of early cardiovascular changes in patients with RA, they added. Limitations of the study were the small number of controls and the fact that patients were already taking anti-rheumatic drugs and steroids at the time of the initial ultrasound. Complete five-year follow-up of all cases and controls is planned.

View the article online

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

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Ultras Small Transducers Could Bring Ultrasound to the Cellular Level

When it comes to the transducers that power ultrasound, less is more. As they have gotten smaller, more has been packed into the handheld probes that host them, providing more information, allowing easier access to the body’s acoustic windows, and offering easier handling by operators. Now this triad of benefits might be in line for a further boost, a big one. 

The University of Nottingham in the U.K. claims its scientists and engineers have developed the world’s smallest ultrasonic transducers; devices several orders of magnitude smaller than current transducers. They are so tiny that up to 500 of them might be placed across the width of one human hair. 

The work to fabricate these tiny transducers is only in the early stages of development, so there’s no telling where it may lead. But it’s a lot of fun to speculate. Their extraordinarily small size could allow imaging at scales a thousand times finer than is possible now. In theory, so many transducers could be packed on a single probe that sonograms more detailed than the images from today’s most powerful microscopes might be produced. They might be put on the ends of catheters and threaded into the body to produce images of individual cells, a far cry from today’s catheter-borne ultrasound probes that provide a glimpse of the tissues that make up lumen. Or their size might be leveraged to create an ultrasonic frequency whose wavelength is smaller than that of visible light, opening an entirely new vista in sonography. 

These transducers are themselves wonders. Matt Clark of Nottingham’s Applied Optics Group describes them as consisting of sandwich- or shell-like structures that, when hit by a pulse of laser light, begin to ring at a high frequency. The devices can be constructed by either micro- or nanolithography techniques, similar to those used to make microchips, or by molecular self-assembly, whereby the transducers are constructed chemically. 

Medical ultrasound is an odds-on favorite as an applications area, but it is not the only possibility. The nanotransducers might be used in the fundamental life sciences, as a complement to optical microscopy. 

“Imagine imaging inside cells in the same way that ultrasonic imaging is performed inside bodies,” Clark said. “Theoretically, we could get higher resolution with the nano-ultrasonics than you can with optical microscopes.” 

If this is possible, imagine what might be done on the medical front if this and conventional technology were combined. Maybe a hybrid ultrasound probe containing conventional and nanotransducers will provide the means for spotting disease while allowing the operator to cone down to a tight view at the cellular level, the equivalent of a noninvasive biopsy.

View the article online

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

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Subharmonic Breast Ultrasound Technique Shows Promise

A dynamic display method for subharmonic ultrasound imaging may offer considerable added value in detecting breast cancer, according to research published in the August issue of the Journal of Ultrasound in Medicine.

In their small pilot study, researchers led by Jaydev Dave of Thomas Jefferson University (TJU) Hospital in Philadelphia found that this display technique had a higher area under the receiver operator characteristics (ROC) curve than a variety of other ultrasound imaging methods. It also even outperformed mammography.

"Dynamic [cumulative maximum intensity subharmonic imaging] images in conjunction with grayscale ultrasound and [subharmonic imaging] may have the potential to improve diagnosis of breast cancer as compared to using grayscale ultrasound or [subharmonic imaging] data alone," the authors wrote (J Ultrasound Med, August 2010, Vol. 29:8, pp. 1177-1185).

Following up on earlier TJU work demonstrating the potential of subharmonic imaging in breast lesions, the research team sought to examine if cumulative maximum intensity imaging could improve the technology's efficacy. With cumulative maximum intensity imaging, a single image of a vascular structure is presented through maximum intensity projection capture of pixels over consecutive imaging frames, according to the group.

Static cumulative maximum intensity subharmonic imaging yields a composite image summarizing blood flow over multiple frames using the maximum intensity projection technique, while a dynamic mode depicts the gradual inflow pattern of the contrast agent in blood vessels, according to the researchers.

To compare the two methods with other breast imaging techniques, the researchers performed contrast-enhanced subharmonic imaging on 14 women. Scans were conducted using a modified Logiq 9 scanner (GE Healthcare, Chalfont St. Giles, U.K.) that was transmitting at 4.4 MHz and receiving at 2.2 MHz.

Baseline scans of grayscale ultrasound and power Doppler imaging were performed after mammography. The researchers also provided contrast-enhanced power Doppler imaging and regular grayscale subharmonic imaging after contrast agent administration; six patients received 0.5 mL of Optison (GE), while eight had 0.25 mL of Definity (Lantheus Medical Imaging, North Billerica, MA).
Grayscale subharmonic imaging was performed after a second contrast dose was administered (4.0 mL of Optison or 1.4 mL of Definity) following a 15-minute interval.

All patients received a core biopsy for histopathologic assessment following ultrasound. To reduce noise and blurring and compensate for motion artifacts, the researchers deployed a new automated motion compensation algorithm for both imaging modes.

After an initial phase of the study established the optimal threshold for the automated algorithm, a radiologist with more than 17 years of breast imaging experience compared the imaging techniques. Blinded to mammographic and pathologic findings, the radiologist evaluated the ultrasound clips on a six-point scale ranging from 0 (no lesion) to 5 (malignant findings).

Over a 2.5-year period and with at least a three-month interval between each review session, the radiologist reviewed the images in the following order:

1. Standard grayscale
2. Standard grayscale and precontrast power Doppler imaging
3. Standard grayscale and contrast-enhanced power Doppler imaging
4. Standard grayscale and subharmonic imaging
5. Standard grayscale, subharmonic imaging, and static cumulative maximum intensity subharmonic imaging
6. Standard grayscale, subharmonic imaging, and dynamic cumulative maximum intensity subharmonic imaging

The area under the ROC curve (which shows the incremental value for each modality) for diagnosing breast cancer for each method were as follows:

• Grayscale: 0.64
• Power Doppler imaging: 0.64
• Contrast-enhanced power Doppler imaging: 0.67
• Mammography: 0.76
• Subharmonic imaging: 0.78
• Static cumulative maximum intensity display mode for subharmonic imaging: 0.75
• Dynamic cumulative maximum intensity display mode for subharmonic imaging: 0.90

The higher area under the ROC curve for the dynamic cumulative maximum intensity display mode over mammography was statistically significantly (p = 0.03).

In other findings, the combination of standard grayscale, subharmonic imaging, and dynamic cumulative maximum intensity subharmonic imaging had a sensitivity of 100%, specificity of 50%, accuracy of 63%, positive predictive value of 40%, and negative predictive value of 100%.

In comparison, mammography alone had a sensitivity of 100%, specificity of 20%, accuracy of 38%, positive predictive value of 27%, and negative predictive value of 100%. Standard grayscale ultrasound and precontrast power Doppler imaging both turned in 50% sensitivity, 92% specificity, 81% accuracy, 67% positive predictive value, and 85% negative predictive value.

Standard grayscale ultrasound and postcontrast power Doppler imaging had 75% sensitivity, 75% specificity, 75% accuracy, 50% positive predictive value, and 90% negative predictive value. The combination of standard grayscale ultrasound and subharmonic imaging yielded 75% sensitivity, 83% specificity, 81% accuracy, 60% positive predictive value, and 91% negative predictive value.

The authors noted that their long-term goal is to demonstrate that dynamic cumulative maximum intensity subharmonic imaging can help characterize breast lesions by showing composite vascular tumor morphology. "The improved detection with dynamic [cumulative maximum intensity subharmonic imaging] calls for a larger clinical trial for this technique before implementing it in a clinical environment," the researchers concluded. "The technique may then be used as an adjunct to mammography and standard ultrasound, which may increase the specificity of breast cancer characterization (consistent with one of the goals of the U.S. Preventive Services Task Force in updating their recommendation in 2009 for biennial breast screening examinations)."

In discussing the study at last month's American Association of Physicists in Medicine (AAPM) meeting in Philadelphia, co-author Flemming Forsberg, PhD, said that the group has received funding from the U.S. National Institutes of Health (NIH) to conduct a large-scale, four-year trial at two centers with the goal of including data from 450 women.

View the article online

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

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