Physician’s Brief clinical and research highlights for our colleagues in urology Ye a r- E n d 2014
Histotripsy: Non-invasive, Mechanical Tissue Ablation New U-M-developed technology begins clinical trials A revolutionary method of tissue ablation has now entered early clinical trials at the University of Michigan. This technology, called histotripsy, was conceived by scientists and clinicians at U-M, and it has the potential to treat a wide variety of disorders. Histotripsy is a form of focused ultrasound that uses a mechanical process — not heat, like other focused ultrasound modalities — to ablate tissue. The mechanical process of histotripsy creates extreme pressure changes, causing microbubbles to form in the tissue, a process called cavitation. “When you create very low pressure, dissolved gas and water vapor come out of solution,” explains William W. Roberts, M.D., associate professor of Urology and Biomedical Engineering. “These bubbles oscillate, coalesce and collapse, releasing a tremendous amount of
William Roberts, M.D., combined his expertise in urology and biomedical engineering to pioneer urologic applications of histotripsy.
energy in a very confined space, which mechanically homogenizes the tissue.”
pressure can be precisely confined, allowing non-invasive “sculpting” of tissues.
One of the main advantages to histotripsy is its precision. Most other types of ablation — other forms of ultrasound, radiofrequency and microwave — have trouble controlling the spread of heat. With histotripsy, induced
“Additionally, histotripsy can be viewed in real time during the ablative process, because the microbubbles appear bright white on ultrasound imaging,” says Roberts. “It’s easy to see exactly where the cavitation activity Continued on page 2
Continued from page 1 occurs, unlike other ablative modalities whose results cannot be easily imaged until long after the procedure.”
First clinical trial: BPH As a urologist, Roberts was naturally interested in the urologic applications of histotripsy. So benign prostatic hyperplasia (BPH) was chosen as the first disease to be studied with the technology. The traditional surgical treatment of BPH is transurethral resection of the prostate (TURP), which is effective but requires significant time under anesthesia. This is increasingly relevant, as widespread use of medical management for BPH means the current patient population needing TURP is much older and at higher risk for complications than in the past. Using histotripsy for BPH eliminates prostate tissue and debulks the transition zone in pre-clinical studies. This research showed enough promise for FDA
approval of the current pilot clinical trial to evaluate safety in humans. This trial at the University of Michigan, led by principal investigator John Wei, M.D., has successfully completed enrollment. It is anticipated that a larger multicenter trial and more enrollment opportunities will follow. “Although initially we are exploring histotripsy as a BPH treatment, it’s really a platform technology,” explains Roberts. “It could potentially change paradigms for how surgical diseases are treated. Currently, researchers and clinicians are also looking at how histotripsy might be used to treat prostate cancer, small renal masses in the kidney, stone disease, liver cancer, congenital heart syndromes and thrombosis.”
Born at the University of Michigan Histotripsy was conceived at the University of Michigan over 10
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years ago, and the initial proof of concept was demonstrated by the Histotripsy Research Group, led by Charles A. Cain, Ph.D., professor of Biomedical Engineering and including Roberts and three other Biomedical Engineering faculty: J. Brian Fowlkes, Ph.D., Zhen Xu, Ph.D, and Timothy L. Hall, Ph.D. In 2009, the research group realized the need for a commercial partner to further translate histotripsy for clinical use, so a company called HistoSonics was formed. HistoSonics built the human prototype histotripsy system, the Vortx RX, that was approved by the FDA for the pilot human trial. “This technology and translational research of histotripsy would not be possible without the collaboration and support of many individuals, institutions and foundations,” says Roberts. “So it’s exciting for everyone, because we believe that histotripsy has the potential to transform many areas of surgical and medical care.” Roberts is on faculty at University of Michigan and is a member of the Histotripsy Research Group. In addition, he also consults for HistoSonics, serves as chairman of its Clinical Advisory Board and is a founder of the company.
Mi-Prostate Score Test Improves on PSA for Predicting Cancer U-M leads development of early detection test for prostate cancer More than 1 million men will undergo a prostate biopsy this year, but only about one-fifth of those biopsies will result in a cancer diagnosis. The reason is that the traditional prostate cancer screening test – a blood test to measure prostate specific antigen, or PSA—does not give doctors a complete picture. Now, the University of Michigan Health System has begun offering a new urine test called Mi-Prostate Score to improve on PSA screening for prostate cancer. The test incorporates three specific markers that could indicate cancer and studies have shown that the combination is far more accurate than PSA alone.
urine samples. Mi-Prostate Score, or MiPS, was significantly more accurate than PSA alone for predicting cancer as well as predicting aggressive prostate cancer that is likely to grow and spread quickly.
“Many more men have elevated PSA than actually have cancer but it can be difficult to determine this without biopsy. We need new tools to help patients and doctors make better decisions about what to do if serum PSA is elevated. Mi-Prostate Score helps with this,” says Scott Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University of Michigan. Researchers validated the new test on nearly 2,000
Mi-Prostate Score developed from a discovery in the lab of Arul Chinnaiyan, M.D., Ph.D., in 2005 of a genetic anomaly that occurs in about half of all prostate cancers, an instance of two genes changing places and fusing together. This gene fusion, T2:ERG, is believed to cause prostate cancer. Studies in prostate tissues show that the gene fusion almost always indicates cancer. The new urine test looks for the
Arul Chinnaiyan, M.D., Ph.D., and Scott Tomlins, M.D., Ph.D.
Disclosure: The University of Michigan has been issued a patent on the detection of ETS gene fusions in prostate cancer, on which Tomlins and Chinnaiyan are listed as co-inventors. The diagnostic field of use has been licensed to Hologic. Chinnaiyan has served as a consultant to Hologic.
T2:ERG fusion as well as another marker, PCA3. This is combined with serum PSA measure to produce a risk assessment for prostate cancer. The test also predicts risk for having an aggressive tumor, helping doctors and patients make decisions about whether to wait and monitor test levels or pursue immediate biopsy. “This combination test is not designed to say definitively at diagnosis whether a man has aggressive prostate cancer, but it can provide a more accurate estimate of the likelihood of having cancer and the likelihood of that cancer being aggressive,” Tomlins says.
The test is available to anyone but requires a doctor’s request. For further information, call the University of Michigan’s MLabs at 800-862-7284.
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