The researchers believe their test ‘could reduce the number of unnecessary prostate cancer biopsies by 32%,’ UEA reported
New diagnostic technologies may make it possible for men to provide a urine sample that can allow a clinical laboratory to not only accurately diagnose prostate cancer but also help determine whether it is an aggressive form of prostate cancer. Researchers in the United Kingdom (UK) recently described just such a test in an online, peer-reviewed journal.
Development of a non-invasive method of diagnosing prostate cancer would be significant for anatomic pathologists in the United States. In the US alone, approximately 248,000 men will be diagnosed with this type of cancer in 2021. Prostate biopsies represent a major proportion of case referrals to community pathology groups.
Moreover, were such a non-invasive test for prostate cancer also able to identify those individuals with fast-growing prostate cancers, that would help urologists make more informed treatment decisions.
A Disease Men More Commonly Die ‘With’ Rather than ‘From’
According to CDC statistics, most men over the age of 80 will have some form of slow-growing prostate cancer when they die. However, a percentage of men each year contract a rapidly growing aggressive form of the cancer, and until recently, diagnosing which cancer a patient was fighting often required multiple invasive prostate needle biopsies. But that may soon change.
Researchers at the University of East Anglia (UEA) Norwich Medical School in the United Kingdom (UK) have developed a non-invasive urine test for prostate cancer that they say also can determine the aggressiveness of the disease. Knowing this may help physicians better assess a patient’s risk prior to ordering invasive needle biopsies, a UEA article notes.
The UEA test may also allow for self-collection of the biological sample, and if it proves accurate, the test could bring additional revenue to clinical laboratories that would perform the urine testing.
“In this work we develop a test that predicts whether a patient has prostate cancer and how aggressive the disease is from a urine sample. This model combines the measurement of a protein-marker called EN2 and the levels of 10 genes measured in urine and proves that integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy,” they wrote.
“While prostate cancer is responsible for a large proportion of all male cancer deaths, it is more commonly a disease men die with rather than from,” said Daniel Brewer, PhD, one of the lead researchers on this study. “Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimize over-diagnosis and overtreatment whilst appropriately treating men with aggressive disease, especially if this can be done without taking an invasive biopsy.
“Invasive biopsies come at considerable economic, psychological, and societal cost to patients and healthcare systems alike,” he added. Brewer is Senior Lecturer in Cancer Bioinformatics and a group leader within the Cancer Genetics Team at UEA’s Norwich Medical School.
“Our new urine test not only shows whether a patient has prostate cancer, but it importantly shows how aggressive the disease is. This allows patients and doctors to select the correct treatment,” said Daniel Brewer, PhD (above), Senior Lecturer and Lead Researcher, UEA Norwich Medical School, in the news release. (Photo copyright: Eastern Daily Press.)
Possibility of Reducing Needle Biopsies by 32%
Called “ExoGrail,” the UEA’s new test builds on their earlier development of the Prostate Urine Risk (PUR) and ExoMeth tests. The test works by integrating two biomarkers.
Levels of gene expression of 10 genes related to prostate cancer.
The researchers tested ExoGrail on urine samples from 207 patients at Norfolk and Norwich University Hospital (NNUH) who also had needle biopsy samples available.
According to the published study, the UEA ExoGrail urine test enabled:
Results comparable to the biopsy findings.
Identification of people with prostate cancer and people without it.
Risk scoring that noted aggressive prostate cancer and need for biopsy.
Potential to reduce unnecessary biopsies by 32%.
“ExoGrail resulted in accurate predictions even when serum PSA [protein-specific antigen] levels alone proved inaccurate; patients with a raised PSA but negative biopsy result possessed ExoGrail scores significantly different from both clinically benign patients and those with low-grade Gleason 6 disease, whilst still able to discriminate between more clinically significant Gleason ≥ 7 cancers,” the researchers stated in their published study.
“The adoption of ExoGrail into current clinical pathways for reducing unnecessary biopsies was considered, showing the potential for up to 32% of patients to safely forgo an invasive biopsy without incurring excessive risk,” they noted.
Prostate Cancer Patients May Soon Have Options
While more research is needed, the new UEA Norwich Medical School ExoGrail test introduces compelling non-invasive methods for diagnosing prostate cancer. Patients with findings of aggressive cancer can proceed to biopsies, while others determined to have non-aggressive forms of prostate cancer may be able to avoid more invasive tests and the associated costs and stress.
Additionally, men may soon be able to collect their own specimens without the need to visit the primary care doctor or a patient service center.
A follow-up study underway at the University of East Anglia and the NNUH involves sending 2,000 men in the UK, Europe, and Canada home testing “prostate screening boxes” to “to collect men’s urine samples at-home,” according to a UEA new release, which noted that “the Prostate Screening Box has been developed in collaboration with REAL Digital International Limited to create a kit that fits through a standard letterbox.”
“We have developed the PUR (Prostate Urine Risk) test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk,’” said Jeremy Clark, PhD, Senior Research Associate at UEA’s Norwich Medical School.
“The Prostate Screening Box part sounds like quite a small innovation, but it means that in future the monitoring of cancer in men could be so much less stressful for them and reduce the number of expensive trips to the hospital,” he added.
Anatomic pathologists and clinical laboratory managers will want to follow the progress of these clinical studies. A non-invasive, urine-based test for prostate cancer could be a game-changer if it can detect prostate cancer with comparable accuracy to the tissue-based diagnostics that are the current standard of care in the diagnosis of prostate cancer.
This new technology could replace needle biopsies and allow physicians to detect rejection of transplanted organs earlier, saving patients’ lives
Anatomic pathologists
may be reading fewer biopsy reports for patients with organ transplants in the
future. That’s thanks to a new technology that may be more sensitive to and
capable of detecting organ rejection earlier than traditional needle biopsies.
When clinicians can detect organ transplant rejection
earlier, patients survive longer. Unfortunately, extensive organ damage may
have already occurred by the time rejection is detected through a traditional
needle biopsy. This led a group of researchers at Emory University School of Medicine to
search for a better method for detecting organ rejection in patients with transplants.
The Emory researchers describe the method and technology
they devised in a paper published in Nature Biomedical
Engineering, titled, “Non-Invasive Early Detection of Acute Transplant
Rejection Via Nanosensors of Granzyme B Activity.” The new technology could
make it easier for clinicians to detect when a patient’s body is rejecting a
transplanted organ at an earlier time than traditional methods.
This technology also provides a running measure of processes,
so clinicians have more powerful tools for deciding on the most appropriate
dosage of immunosuppressant
drugs.
“Right now, most tests are aimed at organ dysfunction, and
sometimes they don’t signal there is a problem until organ function is below 50
percent,” Andrew
Adams, MD, PhD Co-Principal Investigator and an Associate Professor of Surgery
at Emory University School of Medicine, in a Georgia
Institute of Technology news release.
How the Technology Works
The method that Adams and his colleagues tested involves the
detection of granzyme B,
a serine protease
often found in the granules of natural killer cells
(NK cells) and cytotoxic
T cells. “Before any organ damage can happen, T cells have to produce granzyme
B, which is why this is an early detection method,” said Gabe Kwong, PhD, Assistant
Professor in the Wallace H. Coulter Department of Biomedical Engineering at
Georgia Tech and Emory University, in the news release.
The new technology is made up of sensor nanoparticles in the
shape of a ball with iron oxide in the middle. Amino acids stick out of the
ball like bristles. Each amino acid has a fluorescent molecule attached to the
tip.
The nanoparticles are injected into the patient. Their size
prevents them from gathering in the patient’s tissue or from being flushed out
through the kidneys. They are designed to accumulate in the tissue of the
transplanted organ.
If the T cells in the transplanted organ begin to produce
granzyme B, the amino acids break away from the nanoparticles, releasing the
fluorescent molecules attached to their tips. Those molecules are small enough
to be processed through the kidneys and can be detected in the patient’s urine.
Pathologists Play Crucial Role on Transplant Teams
Anatomical pathologists (histopathologists in the UK) are key
members of transplant teams for many reasons, including their ability to assess
biopsies. The current method for detecting organ transplant rejection involves
needle biopsies. It is considered the gold standard.
However, according to a paper published in the International
Journal of Organ Transplantation Medicine: “Although imaging studies
and laboratory findings are important and helpful in monitoring of the
transplanted liver, in many circumstances they are not sensitive enough. For
conditions such as rejection of the transplant, liver histology remains the
gold-standard test for the diagnosis of allograft dysfunction. Therefore,
histopathologic assessments of allograft liver
biopsies have an important role in managing patients who have undergone liver
transplantation.”
There are two main problems with needle biopsies. The first,
as mentioned above, is that they don’t always catch the rejection soon enough.
The second is that the needle may cause damage to the transplanted organ.
“The biggest risk of a biopsy is bleeding and injury to the transplanted organ,” noted Andrew Adams, MD, PhD (above), Co-Principal Investigator and an Associate Professor of Surgery at Emory University School of Medicine, in the Georgia Tech news release. “Then there’s the possibility of infection. You’re also just taking a tiny fraction of the transplanted organ to determine what’s going on with the whole organ, and you may miss rejection or misdiagnose it because the needle didn’t hit the right spot,” he added.
And, according to Kwong, even though biopsies are the gold
standard, the results represent one moment in time. “The biopsy is not
predictive. It’s a static snapshot. It’s like looking at a photo of people in
mid-jump. You don’t know if they’re on their way up or on their way down. With
a biopsy, you don’t know whether rejection is progressing or regressing.”
Future Directions of Emory’s Research
The research conducted by Adams and Kwong, et al, is in its
early stages, and the new technology they created won’t be ready to be used on patients
for some time. Nevertheless, there’s reason to be excited.
Nanoparticles are not nearly as invasive as a needle biopsy.
Thus, risk of infection or damaging the transplanted organ is much lower. And Emory’s
technology would allow for much earlier detection, as well as giving clinicians
a better way to adjust the dose of immunosuppressant drugs the patient takes.
“Adjusting the dose is very difficult but very important
because heavy immunosuppression increases occurrence of infections and patients
who receive it also get cancer more often,” said Kwong. The new technology
provides a method of measuring biological activity rates, which would give
clinicians a clearer picture of what’s happening.
The Emory team’s plan is to enhance the new sensors to
detect at least one other major cause of transplant rejection—antibodies. When
a patient’s body rejects a transplanted organ, it produces antibodies to
neutralize what it sees as a foreign entity.
“Antibodies kill their target cells through similar types of
enzymes. In the future, we envision a single sensor to detect both types of
rejection,” said Kwong.
Adams adds, “This method could be adapted to tease out
multiple problems like rejection, infection, or injury to the transplanted
organ. The treatments for all of those are different, so we could select the
proper treatment or combination of treatments and also use the test to measure
how effective treatment is.”
This line of research at Emory University demonstrates how
expanding knowledge in a variety of fields can be combined in new ways. As this
happens, medical laboratories not only get new biomarkers that can be
clinically useful without the need for invasive procedures like needle biopsies,
but these same biomarkers can guide the selection of more effective therapies.
Public health agencies and physicians would gain access to accurate, rapid dip-stick test that could give results similar to a pregnancy test Tuberculosis is a major killer that ranks alongside HIV/AIDS as a leading cause of death worldwide. This deadly disease takes the lives of more than a million people each year. And, unfortunately, traditional medical laboratory testing using X-rays, blood/skin/sputum specimens, or the new molecular diagnostic systems can be time consuming and expensive....
National Health Service estimates 73% of 65-million urine specimens collected annually in the UK are contaminated
Wanting to know why so many female patients that present with urinary tract infections (UTIs) require repeat appointments, Dr. Vincent Forte, a family GP and forensic physician who worked for the National Health Service (NHS) for 26 years, began investigating. He determined that the standard urine specimen collection cup is primarily the cause of poor-quality medical laboratory test results.
Forte realized that the method of collecting the specimens was largely to blame, with the required “start-aim-start” midstream collection technique required by traditional polypropylene specimen cups at the root of the problem.
Healthcare professionals, whether working in clinical laboratories and anatomic pathology groups or hospitals and out-patient clinics, often are among the first to notice when gaps in the quality or integrity of medical laboratory test results exist. However, in this case, it was a general practice physician rather than a medical laboratorian or in vitro diagnostics (IVD) manufacturer that set out to solve the problem of poor urine specimen collection, which The Daily Telegraphreports results in 73% of the 65-million urine specimens collected annually by the NHS being unreliable. That’s 47.5-million unreliable medical laboratory specimens collected and tested yearly in the United Kingdom.
Accurate Urine Collection Brings Billions in Savings
Vincent Forte concluded that the quality gap in urine specimen collection for his female patients was preventing accurate first-time analysis, diagnosis, and targeted treatment. In 2001, he set out to re-engineer urine collection cups. His first design—“a simple flushable paper funnel, which rejected first-flow urine, collected midstream, and ejected the remainder”—established the underlying design principle behind the patented Peezy Midstream product, Giovanna Forte stated in the RSA blog post.
Giovanna Forte noted that the first version of the device, marketed in 2010, was a “funnel formed by flat-sheet film, with a unique container-acceptor,” with overflow duct and incorporating a compressed sponge that rejects the first 8-10 ml of urine. While the product was well received, Forte says the selling price was too expensive to meet the NHS requirement for cost savings. By 2012, the product evolved into an injected-modeled design, which cut production costs by 50%. By 2014, the ergonomically designed funnel was improved to incorporate the two most common urine collection tubes.
In a Forte Medical presentation, Giovanna Forte predicted that accurate urine collection could result in a £1.2-billion (US $1.56-billion) savings to the NHS.
A Design Week article described the testing process for developing the midstream specimen collection device as “similar to launching a website in beta,” with initial testing resulting in changes such as the creation of a flatter, rounder handle to make the product easier to hold.
“Within the NHS, I was allowed to attend clinics where evaluations were taking place and speak directly to the patients. This allowed me to find out what they thought of everything from instructions for use to the collection system itself,” Vincent Forte stated in the Design Week article. “All the information was fed back into our design engineers, who proposed an improved product made more simply at a lower price.”
The patented Peezy Midstream urine collection system rejects the first (often contaminated) 8-10 ml of urine, isolating and capturing the important midstream and rejecting the rest of the urine into the toilet. The product claims 98.5% accurate urine specimen collection and would improve the accuracy and reliability of the medical laboratory tests performed on urine samples collected with this device. (Photo copyright: Forte Medical.)
1. Peezy Midstream PE40, which collects urine into a traditional 30ml universal container; and
2. Peezy Midstream PE50, which collects urine into a lab-friendly 10ml primary tube designed to fit in laboratory analyzers.
“This simple solution … took 10 years and £2.6-million [US $3.38-million] to get right. It was achieved not by a multinational with deep pockets, but by a startup funded largely by friends, family, and a handful of angel investors, along with the goodwill of design and manufacturing partners,” Vincent Forte stated in the RSA blog post.
Specimen Capture Methods Lead to Careless Infection Control
In an article published on News Medical, an online, open-access medical information provider, Giovanna Forte points out another flaw in traditional urine collection systems.
“Thrusting one’s hands willingly into our own urine is hardly common practice. That we are expected to do so in order to capture an important specimen essential to diagnosis hardly chimes with the concept of modern medicine and leads to pretty shabby infection control by any standards,” she stated.
Still to come are clinical trials and papers in peer-reviewed medical journals that support the function of this medical device to improve patient care. It is notable, though, that the National Health System in the UK is collaborating with Forte Medical in certain ways to determine how the device can improve patient care. Dark Daily would like to hear from any medical laboratories in the UK and USA that are using this device when urine specimens are collected.
A legal, supervised injection site (SIS) affiliated with Vancouver Coastal Health found 86% of drugs tested with strips contained fentanyl when tested with these medical lab test kits
Here’s an unexpected application of point-of-care testing (POCT) that may surprise pathologists and medical laboratory leaders. In a sort of “guerilla-warfare” street experiment that applies diagnostic technologies to a problem, the manager of a needle-exchange program in the Bronx has been helping heroin and other opioid users discover if a product they are about to ingest is contaminated by handing out test strips designed for testing urine.
The addicts participating in these special programs use the POCT urine test strips to test their drugs for the presence of fentanyl, a powerful synthetic opioid analgesic similar to morphine that can increase the potency of opioids to lethal levels. Rehab program directors adopted this approach to help prevent overdoses and deaths among drug users.
Reducing Overdoses with Test Strip Handouts
Opioids such as morphine are often prescribed to cancer or surgery patients to treat severe pain. However, according to a National Institute on Drug Abuse (NIDA) fact sheet, fentanyl is “50 to 100 times more potent than morphine.” When fentanyl is mixed with heroin or cocaine and sold on the streets, the potent mix can be deadly, NIDA explained.
Test strips ordered from Canada designed to check patients’ urine for fentanyl are being used by St. Ann’s Corner of Harm Reduction (St. Ann’s) in the Bronx, New York. The strips are being used to check drug users’ syringes for fentanyl, according to a National Public Radio Shots article. The idea is to inform drug users of what they have in hand and possibly encourage them to choose not to take the drug, use less, or slow things down, Shots reported.
“If you’re doing dope, we’ll give you a test strip so you can test and see if there’s fentanyl,” stated Van Asher, Data Manager at St. Ann’s, in the Shots article.
Whether an unlicensed individual distributing test strips to drug users violates state or federal regulations was not broached in the Shots article.
St. Ann’s gives out about 15 strips a day each costing $1, Shots noted. St. Ann’s staff is sharing data collected on the encounters with the Centers for Disease Control and Prevention (CDC) and with New York health departments.
Finding Fentanyl with Test Strips in Canada
St. Ann’s isn’t the first to use urine test strips for drug checking. Vancouver Coastal Health (VCH) in British Columbia, Canada, launched a pilot program for drug-checking in 2016 at its Insite facility.
At Insite’s “supervised injection site” facility (above) in Vancouver, British Columbia, drug users can “legally” inject illegal drugs. Directors of this program have adapted point-of-care urine test kits typically used in medical laboratory testing to allow drug users to test their heroin and opiate drugs for the presence of fentanyl. The goal is to reduce overdoses and deaths from users unknowingly ingesting fentanyl. (Photo copyright: CBCNews.)
Insite began to test drugs for the presence of fentanyl in the fall of 2016. Data from 173 tests performed in July and August found that 86% of drugs tested contained fentanyl, noted a VCH news release.
“These initial results confirm our suspicion that the local drug supply is overwhelmingly contaminated with fentanyl. We’re hoping this information can help people who use drugs,” stated Mark Lysyshyn, MD, MPH, VCH Medical Health Officer and Professor of Medicine at University of British Columbia.
The test works when the client dilutes the substance with a few drops of water. A positive or negative result for fentanyl is revealed within seconds.
The test strip used by Insite was designed to check for fentanyl in urine, not for checking drugs, noted the VCH statement. Insite intends to review the pilot program test data and decide whether to continue testing services after the pilot program concludes.
Alexander Walley, MD, Director of the Addiction Medicine Fellowship Program and Assistant Professor of Medicine at Boston Medical Center, stated the test may aid users’ decision-making.
“Even when they know they’re going to be positive for fentanyl, the experience of somebody testing their drugs and seeing that it’s fentanyl has an impact. It really encourages them to use more safely,” he stated in the Shots article.
Overdose Deaths Due to Fentanyl in America
A CBC News, Manitoba, article called the death rate due to fentanyl ingestion a “Canada-wide disaster.” However, the problem is significant in the US as well.
Death rates from synthetic opioids, including fentanyl, rose more than 72% from 2014 to 2015 in the US, according to the CDC.
In New York City, fentanyl is increasingly being linked to overdoses. In 2016, nearly half (44%) of drug deaths involved drugs mixed with fentanyl. That’s a 16% increase over 2015, according to a NYC Health press release.
A report from the Tennessee Department of Health noted that 1,451 people died from drug overdose in 2015. That’s a state record. Deaths associated with fentanyl rose significantly from 69 in 2014 to 174 in 2015, the report noted.
How Fentanyl Works and Why It Is Dangerous
Here are some fentanyl facts from the NIDA:
Fentanyl works by binding to opioid receptors located in areas of the brain that control pain and emotions;
People may experience side effects such as euphoria, drowsiness, nausea, confusion, addiction, respiratory arrest, unconsciousness, coma, and death;
Increased risk of overdose exists when drug users are unaware a drug they are ingesting contains fentanyl.
Clinical laboratory directors and pathology groups nationwide might want to follow the progress of test strip services at St. Ann’s Corner and Insite’s SIS. This twist on traditional POCT—using urine test strips to look for the presence of fentanyl in substances—could aid their own communities achieve public awareness, change behaviors, and save lives.
