Johns Hopkins researchers make progress in the development of noninvasive urine test for prostate cancer

Researchers at the Johns Hopkins Kimmel Cancer Center have made significant progress toward development of a simple, noninvasive liquid biopsy test that detects prostate cancer from RNA and other specific metabolic chemicals in the urine.

A description of their findings appears in the Feb. 28 issue of the journal Scientific Reports.

The investigators emphasize that this is a proof-of-principle study for the urine test, and it must be validated in additional, larger studies before it is ready for clinical use.

The researchers used RNA deep-sequencing and mass spectrometry to identify a previously unknown profile of RNAs and dietary byproducts, known as metabolites, among 126 patients and healthy, normal people. The cohort included 64 patients with prostate cancer, 31 with benign prostatic hyperplasia and prostatitis diseases, and 31 healthy people with none of these conditions. RNA alone was not sufficient to positively identify the cancer, but addition of a group of disease-specific metabolites provided separation of cancer from other diseases and healthy people.

"A simple and noninvasive urine test for prostate cancer would be a significant step forward in diagnosis. Tissue biopsies are invasive and notoriously difficult because they often miss cancer cells, and existing tests, such as PSA (prostate-specific antigen) elevation, are not very helpful in identifying cancer," says Ranjan Perera, Ph.D., the study's senior author. Perera is also the director of the Center for RNA Biology at Johns Hopkins All Children's Hospital, a senior scientist at the Johns Hopkins All Children's Cancer & Blood Disorders Institute and the Johns Hopkins All Children's Institute for Fundamental Biomedical Research, and an associate professor of oncology at the Johns Hopkins University School of Medicine and Johns Hopkins Kimmel Cancer Center member.

We discovered cancer-specific changes in urinary RNAs and metabolites that -- if confirmed in a larger, separate group of patients -- will allow us to develop a urinary test for prostate cancer in the future."  Bongyong Lee, Ph.D., study's first author and a senior scientist at the Cancer & Blood Disorders Institute.

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Researchers design home urine test for prostate cancer

Men will now be able to detect prostate cancer at home by just collecting their urine samples as researchers have developed a simple testing method.

Scientists pioneered the test which diagnoses aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods.

Their latest study shows how the ‘PUR’ test (Prostate Urine Risk) could be performed on samples collected at home, so men don’t have to come into the clinic to provide a urine sample - or have to undergo an uncomfortable rectal examination.

This is an important step forward because the first urination of the day provides biomarker levels from the prostate that are much higher and more consistent. And the research team hopes that the introduction of the ‘At-Home Collection Kit’ could revolutionise the diagnosis of the disease.

“Prostate cancer is the most common cancer in men in the UK. It usually develops slowly and the majority of cancers will not require treatment in a man’s lifetime. However, doctors struggle to predict which tumours will become aggressive, making it hard to decide on treatment for many men,” said Lead researcher Dr Jeremy Clark, from UEA’s Norwich Medical School.

“The most commonly used tests for prostate cancer include blood tests, a physical examination known as a digital rectal examination (DRE), an MRI scan or a biopsy. We developed the PUR test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or ‘low risk’, Clark continued.

“Because the prostate is constantly secreting, the collection of urine from men’s first urination of the day means that the biomarker levels from the prostate are much higher and more consistent, so this is a great improvement. Being able to simply provide a urine sample at home and post a sample off for analysis could really revolutionise the diagnosis,” Clark added.

“It means that men would not have to undergo a digital rectal examination, so it would be much less stressful and should result in a lot more patients being tested,” said Clark in the study published in - BioTechniques.

The research team provided 14 participants with an At Home Collection Kit, and instructions. They then compared the results of their home urine samples, taken first thing in the morning, with samples collected after a digital rectal examination.

“We found that the urine samples taken at home showed the biomarkers for prostate cancer much more clearly than after a rectal examination. And feedback from the participants showed that the at-home test was preferable,” revealed Clark.

“Using our At Home test could in future revolutionise how those on ‘active surveillance’ are monitored for disease progression, with men only having to visit the clinic for a positive urine result. This is in contrast to the current situation where men are recalled to the clinic every six to 12 months for painful and expensive biopsies,” continued Clark.

“Because the PUR test accurately predicts aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods - it means that a negative test could enable men to only be retested every two to three years, relieving stress to the patient and reducing hospital workload,” added Clark. 

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Urine test may help prevent cervical cancer, finds study

Urine testing may be as effective as the smear test at preventing cervical cancer and could significantly increase participation rates for screening, a study has found.

The research found that urine testing was just as good as the cervical smear at picking up high-risk human papillomavirus (HPV), the virus that causes cervical cancer.

Researchers  said a urine test could help increase the numbers of women who are screened for cervical cancer.

Urine testing could have a role in the developing world, where cervical cancer is up to 15 times more common and smear testing largely non-existent.

Around one in 20 women show abnormal changes which might go on to become cancer and are referred for colposcopy, where the cervix is examined under magnification, allowing abnormal areas to be seen, sampled and treated, before they ever cause cancer, researchers said.

According to the team, cervical smear samples, self-collected vaginal samples and urine samples are all effective at picking up high risk HPV infection.

Cervical cancer is most common in women aged 30 to 35 years. However, the precancerous stage is detectable in the 5-10 years before this, when up to a third of women fail to attend for their smear test.

"We're really very excited by this study, which we think has the potential to significantly increase participation rates for cervical cancer screening in a key demographic group," said the researcher who led the study. 

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Experts recommend blood, urine testing to diagnose rare adrenal tumors

The Endocrine researcherrs today issued a Guideline (CPG) for the diagnosis and treatment of two types of rare adrenal tumors – pheochromocytomas and paragangliomas – that can raise the risk of cardiovascular disease and even death if left untreated.

Pheochromocytomas are rare, usually non-cancerous tumours that form inside the adrenal glands, while paragangliomas are similar tumors that develop outside the glands. The tumors cause the body to produce excess amounts of the hormones epinephrine – commonly known as adrenaline – and norepinephrine, which is involved in regulating blood pressure. Symptoms of these tumors include high blood pressure, episodic severe headaches, excess sweating, racing heart, feelings of anxiety and trembling.

Experts estimate between 0.1 and 1 percent of patients treated for high blood pressure have pheochromocytomas, according to the scientists."Correctly diagnosing pheochromocytomas and paragangliomas is extremely important," said the  author. "In addition to the strain these tumors put on the cardiovascular system, between 10 and 17 percent of the tumors can become malignant. Researchers have discovered that at least a third of people with these conditions have a disease-causing genetic mutation, so early detection can benefit family members who may be at risk."
The scientist recommends that initial testing for pheochromocytomas and paragangliomas include blood or urine tests for metanephrines – the products left behind when the body metabolizes epinephrine and norepinephrine. Research has shown blood and urine testing for metanephrines are more effective at identifying patients who have pheochromocytomas or paragangliomas than other testing techniques.

Other recommendations from the research include:

• People who are diagnosed with pheochromocytomas or paragangliomas should be involved in a shared decision-making process with their physicians to evaluate the need for genetic testing;
• A diagnostic algorithm that takes into account risk factors such as age at tumour presentation and family history should be used to establish which patients would benefit most from genetic testing and which specific gene mutations to test for;
• People with paragangliomas and those diagnosed with metastatic tumors should be tested for specific gene mutations associated with those conditions;
• Computed tomography can be used as the first choice imaging technology for determining the location of pheochromocytomas or paragangliomas for surgical treatment;
• MRI imaging technology is to be used in specific situations, including for patients who have metastatic tumors, for detecting head and neck paragangliomas and for patients in whom radiation exposure should be limited; and
• Another imaging technology, 18F-fluorodeoxyglucose-positron emission tomography/computed tomography, can be used in patients with metastatic tumours.                                      
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5 Signs You May Have a UTI — and What To Do About It

If you have female anatomy, it's not unlikely you’ve had a urinary tract infection (UTI) at some point. According to the statistics some 40 to 60 percent of women will develop a UTI in their lifetime — and UTIs usually don't only strike once. “In adult women, UTIs are quite common, with women having about one infection every two years,” a physician says. An OB/GYN and maternal fetal medicine expert says UTIs “represent an infection caused by bacteria growing within the urinary system." And it’s the makeup of the female anatomy that makes us so prone to contracting that infection: “Women have shorter urethra than men, which allow bacteria a shorter and easier pathway to the bladder,” the Dr. explains.

One of the most common risk factors is sex — “Usually bladder infections arise from fecal contamination of the urethra, which occurs commonly when having sex,” Dr. says — but UTIs can be caused in other ways, too. Dr. notes that anything put inside the vagina — including certain birth control methods — can be the culprit. “Anything requiring placement of objects within the vagina (causing contact with the urethra in the process) will facilitate a UTI,” she says. ”Therefore diaphragms, rings, [and] spermicidal jellies all have an increased risk of causing an inadvertent UTI.”

Aside from that, Dr. says other causes can be pregnancy (pregnant women’s urinary systems don’t empty as fast as they do in the “non-pregnant state,” allowing bacteria to build up); hormonal changes during menopause; recent trauma, surgery, or catheter use; diseases that affect the immune system, such as diabetes; diseases, like multiple sclerosis, that affect the musculature or nerves in the urogenital system; and kidney stones.

Luckily, there are steps you can take to avoid contracting a UTI. “It is always important that women urinate immediately after having sex, in order to clear the urethra of any bacteria that may have been introduced,” Dr.  says. And don’t hold your urine the rest of the day, either — make sure you void frequently, particularly if you’re pregnant. When you wipe, make sure to do so from front to back: “Wiping back to front inoculates bacteria from the rectal area onto the urethra, [potentially] causing a UTI,” Dr. advises. Outside of the bathroom, Dr. says to make sure you stay plenty hydrated (water can flush out the bacteria on its way out of the body via urination), wear cotton underwear (it allows the area to breathe and stay dry), and wash your genital area and hands thoroughly before inserting anything into the vagina.

Despite all of these preventative measures, though, there’s a decent chance you will still contract a UTI at some point — so it’s a good idea to familiarize yourself with some of the most common signs and symptoms. If you experience any of the following, it could mean you have an infection.

1. Painful and Frequent Urination

If you’re going to the bathroom a lot, and only urinating a little when you do, it could very well be a sign of a UTI. “Ninety percent of the time when a healthy adult woman experiences painful urination and feelings of frequent urination, it is a UTI (assuming [she isn’t] experiencing any vaginal discharge),” Dr. says. The Dr. also notes that, if you have a UTI, incontinence may occasionally occur as well.

2. Cloudy, Dark, or Bloody Urine

Take note of the appearance of your urine after you go to the bathroom: Its look could be an indicator that you need to head to the doctor. “Many women who have bladder infections may notice that their urine looks cloudy or dark,” Dr. says. “Some may even see blood in their urine.”

3. Strong-Smelling Urine

Sure, you might consider all urine to be “strong-smelling,” but if the odor of yours is even stronger than normal (or perhaps different, or foul), that may also be a sign of a UTI, Dr. says.

4. Fever, Nausea, Chills, and Fatigue

Though they’re not as common as the others, Dr. notes that symptoms can include feeling tired or shaky, nauseous, or feverish, as well as experiencing the chills.

5. Back Pain

UTIs can spread, and when they do, you may experience pain in your back. “With a UTI that has ascended into the kidneys, there may be back pain [that’s] particularly sensitive when one taps on the back where the kidneys are located,” author says.

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If you experience any of the above symptoms and think you might have a UTI, the Dr. notes that most pharmacies do sell over-the-counter urine tests to help you determine if that is, indeed, the case. But it’s also a good idea to just consult your doctor, particularly if your symptoms are serious. “If you have a high fever (more than 100.3 F), back or flank pain, or nausea and vomiting, it may indicate something more serious and you should seek urgent medical attention,” he says.

And whether your symptoms are that intense or not, your doctor can diagnose you based on a urine test or your symptoms alone before helping you determine a course of treatment. “Fortunately, most cases of UTIs can be cured with a short course of antibiotic therapy,” the Dr. says. If you ignore your symptoms and the UTI goes unchecked, though, Dr.  says it could lead to serious health consequences, including permanent kidney or bladder damage, preterm labor (if you’re pregnant), and a “very bad complication known as urosepsis, meaning a bacterial infection origination in the urinary system has gone all through the body, [which] can be life-threatening.” The bottom line: Don’t wait until you’re really sick or have a laundry list of painful symptoms before calling your doctor about a suspected UTI.  

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