Archive for the ‘Diagnostic’ Category

December 19, 2011 Monday – 11:50 am EST inShare 1 Text Size Smaller Normal Larger E-mail Print ‘Fantastic Potential’: Researchers Keep Cells Alive Away From Body

Comments Off
Posted 20 Dec 2011 — by James Street
Category Diagnostic, Personalized, Stem Cell Research, Targeted Cancer Therapy

December 19, 2011 Monday – 11:50 am EST

By Adam Daley

Georgetown researchers say they have just significantly changed biomedical research.

Researchers know that normal cells don’t last long once removed from a human, dividing only a few times in a laboratory setting. Common cancers won’t grow in a lab.

That’s about to change.

Senior investigator, Richard Schlegel, M.D., Ph.D., and chairman of the department of pathology at Georgetown Lombardi Comprehensive Cancer Center, has discovered a way to keep normal cells as well as tumor cells taken from an individual cancer patient alive in the laboratory. The technique could be a critical advance, ushering in a new era of personalized cancer medicine, and has potential application in regenerative medicine.

“Because every tumor is unique, this advance will make it possible for an oncologist to find the right therapies that both kills a patient’s cancer and spares normal cells from toxicity,” said Dr. Schlegel. “We can test resistance as well chemosensitivity to single or combination therapies directly on the cancer cell itself.”

The research team found that inserting a Rho kinase (ROCK) inhibitor and fibroblast feeder cells to cancer and normal cells in a laboratory pushes them to morph into stem-like cells. The cells visibly changed their shape as they reverted to a stem-like state.

“In short, we discovered we can grow normal and tumor cells from the same patient forever, and nobody has been able to do that,” said Dr. Schlegel. “Normal cell cultures for most organ systems can’t be established in the lab, so it wasn’t possible previously to compare normal and tumor cells directly.”

“Today, pathologists don’t work with living tissue. They make a diagnosis from biopsies that are either frozen or fixed and embedded in wax,” added Dr. Schlegel. “In the future, pathologists will be able to establish live cultures of normal and cancerous cells from patients, and use this to diagnose tumors and screen treatments. That has fantastic potential.”

The study, which was funded by grants from the National Institutes of Health, Department of Defense fellowship funding, and an internal grant from Georgetown Lombardi’s Cancer Center Support Grant from the National Cancer Institute, is published online today in the American Journal of Pathology.

Without Autopsies, Hospitals Bury Their Mistakes

Comments Off
Posted 19 Dec 2011 — by James Street
Category Diagnostic, Finance and Politics of cancer research and treatment, Fraud
Thursday 15 December 2011
by: Marshall Allen, ProPublica [3] | Report

When Renee Royak-Schaler unexpectedly collapsed and died on May 22, no one ordered an autopsy.

Not the doctors at Howard County General Hospital in Columbia, Md., where the 64-year-old professor and cancer researcher was pronounced dead.

Not the Maryland Office of the Chief Medical Examiner, which passed on the case because no foul play was involved.

And not Royak-Schaler’s physicians at Johns Hopkins University School of Medicine who had diagnosed cancer in her hip two days beforehand but acknowledged they didn’t know what had caused her unforeseen death.

A half-century ago, an autopsy would have been routine. Autopsies, sometimes called the ultimate medical audit, were an integral part of American health care, performed on roughly half of all patients who died in hospitals. Today, data from the Centers for Disease Control and Prevention show, they are conducted on about 5 percent of such patients.

As Royak-Schaler’s husband, Jeffrey Schaler, discovered, even sudden unexpected deaths do not trigger postmortem reviews. Hospitals are not required to offer or perform autopsies. Insurers don’t pay for them. Some facilities and doctors shy away from them, fearing they may reveal malpractice. The downward trend is well-known — it’s been studied for years.

What has not been appreciated, pathologists and public health officials say, are the far-reaching consequences for U.S. health care of minuscule autopsy rates.

Diagnostic errors, which studies show are common, go undiscovered, allowing physicians to practice on other patients with a false sense of security. Opportunities are lost to learn about the effectiveness of medical treatments and the progression of diseases. Inaccurate information winds up on death certificates, undermining the reliability of crucial health statistics.

It was only because of Royak-Schaler’s connections that her case ended differently. Her colleagues at the University of Maryland School of Medicine urged her husband to authorize an autopsy and volunteered to conduct it for free.

In her case, as in so many, the autopsy revealed a surprise: Royak-Schaler, the renowned cancer researcher, had cancer ravaging her body — in her lungs, kidneys, abdomen and the marrow of her bones. A blood clot, likely related to the tumors, caused her sudden death.

Jeffrey Schaler has wrestled with anger that his wife wasn’t diagnosed sooner but said knowing how she died was better than not.

“There’s a sense of peace that accompanies that knowledge,” he said.

For the last year, ProPublica, PBS “Frontline” and NPR have probed America’s deeply flawed system of death investigation [4], focusing primarily on forensic autopsies, which are conducted by coroners’ offices and medical examiners when there is suspicion of an unnatural death. State laws vary, but the preponderance of deaths that occur in hospitals are considered natural. When deaths are unexplained, unobserved or within 24 hours of admission, hospitals may be required to report them to local coroners or medical examiners, but such  agencies rarely take hospital cases.

Hospital physicians, with consent from patients’ next of kin, may order a clinical autopsy to explore the disease process in the body and determine the cause of death. That was the norm 50 years ago, when the value of the autopsy was considered self-evident.

Fight corporate influence by keeping independent media strong! Click here to make a tax-deductible contribution to Truthout. [5]

“Much of what we know about medicine comes from the autopsy,” said Dr. Stephen Cina, chairman of the forensic pathology committee for the College of American Pathologists. “You really can’t say for sure what went on or didn’t go on without the autopsy as a quality assurance tool.”

Yet, autopsy rates at teaching hospitals, which are typically run on a nonprofit basis and have an educational mission, hover around 20 percent today. At private and community hospitals, which constitute 80 percent of facilities nationwide, rates can be close to zero.

“I know new hospitals are being built these days without a place to do an autopsy,” said Dr. Dean Havlik, the Mesa County, Colo., coroner, who estimated that the overall hospital autopsy rate in his area is less than 1 percent.

Hospitals have powerful financial incentives to avoid autopsies. An autopsy costs about $1,275, according to a survey of hospitals in eight states. But Medicare and private insurers don’t pay for them directly, typically limiting reimbursement to procedures used to diagnose and treat the living. Medicare bundles payments for autopsies into overall payments to hospitals for quality assurance, increasing the incentive to skip them, said Dr. John Sinard, director of autopsy service for the Yale University School of Medicine.

“The hospital is going to get the money whether they do the autopsy or not, so the autopsy just becomes an expense,” Sinard said.

Since a 1971 decision by The Joint Commission, which accredits health-care facilities, hospitals haven’t had to conduct autopsies to remain in good standing. The commission had mandated autopsy rates of 20 percent for community hospitals and 25 percent for teaching facilities, but dropped the requirement. Many hospitals were performing autopsies “simply to meet the numbers” and not to improve quality, said Dr. Paul Schyve, the commission’s senior adviser of health-care improvement.

Doctors, too, have gravitated away from autopsies because of growing confidence in modern diagnostic tools such as CT scans and MRIs, which can identify ailments while patients are still alive.

Still, in study after study, autopsies have revealed that doctors make a high rate of diagnostic errors even with increasingly sophisticated imaging equipment.

A 2002 review of academic studies by the federal Agency for Healthcare Research and Quality found [6] that when patients were autopsied, major errors related to the principle diagnosis or underlying cause of death were found in one of four cases. In one of 10 cases, the error appeared severe enough to have led to the patient’s death.

“Clinicians have compelling reasons to request autopsies far more often than currently occurs,” the agency concluded.

Schyve called the findings of such studies flawed because cases in which autopsies are performed are typically the most complex, making diagnostic errors more likely. The overall error rate is far lower, he said.

But Sinard said so few autopsies are being conducted — one survey found that 63 percent of hospitals in Louisiana performed none in a given year — that doctors and hospitals can’t say for certain how patients are dying. “They’ve never checked,” the Yale pathologist said.

Pathologists interviewed by ProPublica said they often find diagnostic errors. “We often identify things that the imaging study could not,” said Dr. Debra Kearney, director of autopsy pathology at Texas Children’s Hospital.

Autopsies can also be a crucial tool for evaluating and improving medical care.

Dr. Elizabeth Burton, deputy director of the pathology department at Johns Hopkins University School of Medicine, said performing autopsies on patients who have died of hospital-acquired infections helps save others. Infection clusters “go in waves” in hospitals, she said. Physicians have used her findings to change antibiotic regimens, snuffing out the bacterium.

Dr. Renu Virmani, president and medical director of the nonprofit CVPath Institute, has used postmortem examinations to help reform the treatment of heart disease. Virmani and her team have collected about 250 specimens of metal stents removed at autopsy from patients who had procedures to clear blockages from their arteries.

Their work showed that, in certain patients, a type of stent designed to reduce the risk of blood clots was causing delayed healing, inflammation and reactions that could be fatal. As a result, patients who receive these stents are now required to take blood-thinning medication for a year after the procedure.

Sitting in her lab in Gaithersburg, Md., Virmani peers through a microscope at a specimen slide taken from a 61-year-old man who died suddenly in 2004, about four months after receiving a clot-resistant stent. She points out signs of inflammation in the cross-section of his stented artery, describing the swirls and grains, stained pink and purple so they stand out on the slide. The autopsy showed that the stent had led to the patient’s fatal blood clot.

Autopsies should be used to evaluate the effectiveness of other therapies, Virmani said, from chemotherapy to heart-valve replacements. “The only way to learn is through autopsies.”

Hospital autopsies are even rarer when patients older than 60 die in hospitals, representing a lost opportunity to learn about age-related diseases, Burton said. More than 684,000 such patients died in hospitals in 2008 — more than one-quarter of the total deaths in the country — and just 2.3 percent were autopsied, CDC data show.

Without autopsies to confirm patients’ precise causes of death, public health officials say, the health-care system overall suffers. Erroneous information sometimes ends up on death certificates. Broad categories of disease such as cancer are probably accurate, but specifics such as the type of cancer may not be, said Robert Anderson, chief of the mortality statistics branch of the CDC’s National Center for Health Statistics.

“These data are used to set public health priorities, to develop public health programs and allocate resources,” Anderson said. “We do the best that we can given the information we have, but if you put bad information into the system, you’re going to get bad information out.”

In 1999, the Medicare Payment Advisory Commission, or MedPAC, which advises Congress about Medicare, issued a report stating that increasing the rate of clinical autopsies could improve health care and reduce errors.

The report recommended paying pathologists directly for autopsies and giving hospitals bonuses or penalties for hitting or missing target autopsy rates. The advisory group also suggested that Medicare change its hospital regulations to encourage more autopsies and use them as a standard of performance.

But Medicare has not acted upon these recommendations. An official from the Centers for Medicare & Medicaid Services declined ProPublica’s request for an interview, saying the use of autopsies in hospitals “is not within [Medicare’s] bailiwick at all.”

Other organizations that advocate for better medicine, such as the Institute for Healthcare Improvement, National Quality Forum and The Joint Commission, have not pushed for higher levels of autopsies, either, despite the widely held belief  that this could produce improved care.

Raising the rate “is not one of our priorities by any means,” The Joint Commission’s Schyve said.

Dr. George Lundberg, a pathologist and one of the country’s most vocal advocates for increasing the autopsy rate, shakes his head when discussing the medical industry’s apathy about low autopsy rates.  Lundberg, the editor of the journal MedPage Today, said The Joint Commission should re-establish mandatory autopsy rates “like they used to have back in the good old days of quality when we weren’t running away from trying to find the truth [about] our sickest patients.”

One way to shake the complacency, various experts told ProPublica, would be for insurance companies and the government to pay for autopsies. But an official from UnitedHealth Group, the largest health-insurance company in the country, said the autopsy is not reimbursed because it “isn’t a procedure that would prevent or treat a sickness or injury” in a patient.

Virmani called this shortsighted. The cost of an autopsy is small relative to the money spent on drugs, treatment and diagnostic imaging, she said, and the payoff could save lives and money.

“We are letting go of something which we could really use tomorrow to improve the health care of patients,” she said.

‘Cancer’ or ‘Weird Cells’: Which Sounds Deadlier?

Comments Off
Posted 22 Nov 2011 — by James Street
Category Diagnostic
By
Published: November 21, 2011

My friend’s mother got terrifying news after she had a mammogram. She had Stage 0 breast cancer. Cancer. That dreadful word. Of course she had to have surgery to get it out of her breast, followed by hormonal therapy.

Or did she?

Though it is impossible to say whether the treatment was necessary in this case, one thing is growing increasingly clear to many researchers: The word “cancer” is out of date, and all too often it can be unnecessarily frightening.

“Cancer” is used, these experts say, for far too many conditions that are very different in their prognoses — from “Stage 0 breast cancer,” which may be harmless if left alone, to glioblastomas, brain tumors with a dismal prognosis no matter what treatment is tried.

It is like saying a person has “mental illness” when he or she might have schizophrenia or mild depression or an eating disorder.

Now, some medical experts have recommended getting rid of the word “cancer” altogether for certain conditions that may or may not be potentially fatal.

The idea of cancer as a progressive disease that will kill if the cells are not destroyed dates to the 19th century, said Dr. Otis Brawley, chief scientific and medical officer at the American Cancer Society. A German pathologist, Rudolph Virchow, examined tissue taken at autopsy from people who had died of their cancers, looking at the cells under a light microscope and drawing pictures of what he saw.

Virchow was a spectacular artist, and he ended up being the first to describe a variety of cancers — leukemia, breast cancer, colon cancer, lung cancer.

Of course, his patients were dead. So when he noted that aberrant-looking cells will kill, it made sense. The deranged cells were cancers, and cancers were fatal.

Now, Dr. Brawley said, the situation is very different. Instead of taking tissue from someone who died, a doctor takes tissue from a living patient, threading a thin needle into a woman’s breast or a man’s prostate, for example. Then a pathologist looks for abnormal cells.

Yet “how it looks under a microscope,” Dr. Brawley said, “does not always predict.” That is especially true for things like Stage 0 breast cancer or similar conditions in other areas of the body — conditions detected by screening and not by symptoms or by feel.

Researchers have come to appreciate this conundrum.

“The definition of cancer has changed,” said Dr. Robert Aronowitz, a professor of history and sociology of medicine at the University of Pennsylvania.

Many medical investigators now speak in terms of the probability that a tumor is deadly. And they talk of a newly recognized risk of cancer screening — overdiagnosis. Screening can find what are actually harmless, if abnormal-looking, clusters of cells.

But since it is not known for sure whether they will develop into fatal cancers, doctors tend to treat them with the same methods that they use to treat clearly invasive cancers. Screening is finding “cancers” that did not need to be found. So maybe “cancer” is not always the right word for them.

That happened recently with Stage 0 breast cancer, also known as ductal carcinoma in situ, or D.C.I.S. It is a small accumulation of abnormal-looking cells inside the milk ducts of the breast. There’s no lump, nothing to be felt. In fact, Stage 0 was almost never detected before the advent of mammography screening.

Now, with widespread screening, this particular diagnosis accounts for about 20 percent of all breast cancers. That is, if it actually is cancer. After all, it is confined to a milk duct, has not spread into the rest of the breast, and may never spread if left alone — it might even go away.

It could also break free and enter the breast tissue. But for now, it is hard to know in many cases whether it makes any difference to treat D.C.I.S. right away or to wait to see if it spreads, treating it then.

Two years ago, an expert panel at the National Institutes of Health said the condition should be renamed. Get rid of the loaded word “carcinoma,” the panel said. A carcinoma is invasive; D.C.I.S. has not invaded the breast. If those cells do invade, they are no longer D.C.I.S. Then they are cancer. So call the condition something else, perhaps “high-grade dysplasia.”

The word “cancer” is so powerful it overwhelms any conversation about what Stage 0 breast cancer actually is, said Cynthia Pearson, executive director of the National Women’s Health Network. When women contact her group to ask about cancer treatments, “sometimes we’re well into the conversation with them before it comes out that they don’t actually have an invasive cancer.”

The same situation arises with prostate cancer screening.

The pathologist Donald Gleason, who invented Gleason scoring for prostate tumors, wanted to rename a very common tumor — the so-called Gleason 3 + 3 — “adenosis” instead of cancer, Dr. Brawley said. His idea was that by calling a 3 + 3 “cancer,” men and their doctors would feel they had to get rid of it right away.

Despite Dr. Gleason’s wishes, 3 + 3 cells are still called cancer. And despite the panel’s advice about D.C.I.S., that name has not changed either.

Cervical cancer specialists had better luck. In 1988, they changed the name of a sort of Stage 0 of the cervix. It had been called cervical carcinoma in situ. They renamed it cervical intraepithelial neoplasia, Grades 1 to 3, taking away the cancer connotation.

But Dr. Brawley, for one, has not given up on educating doctors and patients about the general inadequacy of the word “cancer.” As he put it, “The movement is not quite dead.”

New model establishes guidelines for earlier cancer detection November 16, 2011

Tumors can grow for 10 years or longer before currently available blood tests will detect them, a new mathematical model developed by Stanford University School of Medicine scientists indicates. The analysis, which was restricted to ovarian tumors but is broadly applicable across all solid tumor types, will be published online Nov. 16 in Science Translational Medicine.

“The study’s results can be viewed as both bad and good news,” said Sanjiv “Sam” Gambhir, MD, PhD, professor and chair of radiology and the study’s senior author. (Sharon Hori, PhD, a postdoctoral scholar in Gambhir’s laboratory, is the lead author.)

The bad news, Gambhir said, is that by the time a reaches a detectable size using today’s available blood tests, it is likely to have metastasized to other areas of the body, making it much more deadly than if it had been caught early on. “The good news is that we have, potentially, 10 or even 20 years to find the tumor before it reaches this size, if only we can improve our blood-based methods of detecting tumors,” he said. “We think our will help guide attempts to do that.”

The study advances previous research about the limits of current detection methods. For instance, it is strikingly consistent with a finding reported two years ago by Stanford biochemistry professor Patrick Brown, MD, PhD, that current tests could not detect tumors early enough to make a significant dent in the mortality rate. There is a push to develop more-sensitive diagnostic tests and find better , and Gambhir’s new model could be an essential tool in this effort. It for the first time connects the size of a tumor with blood biomarker levels being shed by that tumor.

To create their model, Gambhir and Hori used mathematical models originally developed to predict the concentration of drugs injected into the blood as they move in and out of the bloodstream. The investigators linked these to additional models of tumor cell growth.

Tumors don’t secrete drugs, but they can shed telltale molecules into surrounding tissue, from which those substances, known as biomarkers, diffuse into the blood. Some biomarkers may be made predominantly by tumor cells, while others exclusively by them. Either way, these substances can be measured in the blood as proxies for a tumor.

Ads by Google

Single and Over 60? – Meet Amazing Singles at SeniorPeopleMeet.com- See Photos – www.SeniorPeopleMeet.com

Some biomarkers are in wide use today. One is the well-known PSA, for prostate cancer. Another is CA125, for ovarian cancer. But these and other currently used blood tests for cancer biomarkers weren’t specifically developed for early detection, and are generally more effective for relatively noninvasive monitoring of the progress of late-stage tumors or their response to treatment. (Rising blood levels of the substance indicate that the tumor is growing, while declining levels denote possible shrinkage.)

Both CA125 and PSA are also produced, albeit in smaller amounts, by healthy tissue, complicating efforts to detect cancer at an early stage when the tumor’s output of the biomarker is relatively low.

The new mathematical model employs separate equations, each governing the movement of a biomarker from one compartment into the next. Into these equations, one can plug known values — such as how fast a particular type of tumor grows, how much of the biomarker a tumor cell of this type sheds per hour and the minimum levels of the biomarker that must be present in the blood for a currently available assay to detect it.

As a test case, Gambhir and Hori chose CA125, a well-studied biomarker shed into blood by ovarian tumors. Ovarian cancer is a notorious example of a condition for which early detection would make a huge difference in survival outcomes.

CA125 is a protein made almost exclusively by ovarian tumor cells. The pharmacokinetics, metabolic fates, typical amounts secreted by an ovarian cell and other properties of CA125 are all well-known, as are ovarian tumors’ typical growth rates, making it excellent for “road testing” with Gambhir and Hori’s model. CA125 is by no means the ideal biomarker, said Gambhir, just one that can be used to help better understand ideal properties of biomarkers for early ovarian cancer detection.

Applying their equations to CA125, Gambhir and Hori showed that before the currently best available test for CA125 could reliably detect an ovarian tumor, the tumor would need to reach a size of about 1.7 billion cells, or the volume of a cube with about a 2-cm edge. That would take about 10.1 to 12.6 years of development, at typical tumor-growth rates, from the first, single cancer cell.

The model further calculated that a biomarker otherwise equivalent to CA125 but shed only by ovarian tumor cells would allow reliable detection within 7.7 years, when a tumor’s size would be that of a tiny cube about one-sixth of an inch high.

In the last decade, many potential new biomarkers for different cancers have been identified. There’s no shortage of promising candidates — six for lung cancer alone, for example. But validating a biomarker in large clinical trials is a long, expensive process. So it is imperative to determine as efficiently as possible which, among many potential tumor biomarkers, is the best prospective candidate.

“This model could take some of the guesswork out of it,” Gambhir said. “It can be applied to all kinds of solid cancers and prospective biomarkers as long as we have enough data on, for instance, how much of it a tumor cell secretes per hour, how long the biomarker can circulate before it’s degraded and how quickly tumor cells divide.

“We can tweak one or another variable — for instance, whether a biomarker is also made in healthy tissues or just the tumor, or assume we could manage to boost the sensitivity of our blood tests by 10-fold or 100-fold — and see how much it advances our ability to detect the tumor earlier on.”

There are now new detection technologies capable of detecting biomarkers at concentrations as low as a few hundred molecules per mm (cc) of blood. A couple of years ago, Gambhir and his colleagues reported on one such developing technology: so-called magneto-nanosensors that can detect biomarkers with a 100-fold greater sensitivity than current methods.

Better biomarker detection alone might shrink the time an ovarian tumor can grow before detection to about nine years, said Gambhir.

A second priority is to come up with new and better biomarkers. “It’s really important for us to find biomarkers that are made exclusively by ,” he said.

Under the right conditions (a highly sensitive assay measuring levels of a biomarker that is shed only by cancer cells), Gambhir said, the model predicts that a tiny tumor with a volume equivalent to a cube less than one-fifteenth of an inch on a side could be spotted.

Provided by Stanford University Medical Center

Lung Cancer Deaths Not Reduced by Chest X-Ray Screening

By Anna Azvolinsky, PhD | October 26, 2011
 A trial of 154,901 participants between the ages of 55 and 74 sought to address whether performing chest radiographs affects lung cancer incidence and mortality rates from lung cancer. The trial, which randomized people one to one either to annual screening or usual care for four years, found that chest x-rays did not reduce lung cancer mortality.
Both sides of the lungs are visible with a growth on the left side of the lung, which could be lung cancer.

The intervention group was offered annual posteroanterior-view chest radiographs while usual-care patients were not offered interventions. The study is published today, online in the November 2 issue of JAMA (doi:10.1001/jama.2011.1591) and will be presented at the annual meeting of the American College of Chest Physicians (CHEST 2011). The results are part of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Randomized Trial.

Martin M. Oken, MD of the University of Minnesota and Philip C. Prorok, PhD of the Division of Cancer Prevention at the NCI and colleagues analyzed participants at one of ten screening centers in the United States between 1993 and 2001. The demographics of the two groups were similar: half were women, about 45% had never smoked, 42% were former smokers, and 10% were current smokers. A total of 1,213 lung cancer deaths were observed in the x-ray screened group compared to 1230 in the usual care group over a 13-year follow up period. In total, 1,696 lung cancers were detected in the screened group and 1620 were detected in the usual care group. It was not possible to accurately detect overdiagnosis rates.

The authors conclude that “these findings provide good evidence that there is not a substantial lung cancer mortality benefit from lung cancer screening with four annual chest radiographs.” The Mayo Lung Project trial of chest radiograph and sputum cytology screenings completed in the early 1980s also did not show a mortality benefit.

In an accompanying editorial, Harold C. Sox, MD at Dartmouth Medical School highlights that this is one of two complementary lung cancer screening trial results released in the last two months The second is the National Lung Screening Study (NSLT), which found that annual low-dose computed tomography reduced lung cancer mortality by 20% relative to annual chest radiography (“NCI-Funded Study Finds Low-Dose CT Scans Better than X-Rays in Reducing Lung Cancer Mortality,” July 21, 2011, CancerNetwork).

Sox comments that the “PLCO lung cancer study provides convincing evidence that lung cancer screening with chest radiography is not effective.” He highlights that this study is important for putting the question of whether chest radiography is beneficial for decreasing the rate of mortality from lung cancer. According to Sox, “the NLST showed convincingly that early detection can lower the risk of death from lung cancer, a big step forward.” Now, he suggests that a real-world comparison between usual care and low-dose CT is warranted.

High tech detection of breast cancer using nanoprobes and SQUID

Comments Off
Posted 28 Oct 2011 — by James Street
Category Breast Cancer, Diagnostic, HER2/neu, NanoTechnology, Physics and Engineering

Contact: Dr Hilary Glover
hilary.glover@biomedcentral.com
44-020-319-22370
BioMed Central

Mammography saves lives by detecting very small tumors. However, it fails to find 10-25% of tumors and is unable to distinguish between benign and malignant disease. New research published in BioMed Central’s open access journal Breast Cancer Research provides a new and potentially more sensitive method using tumor–targeted magnetic nanoprobes and superconducting quantum interference device (SQUID) sensors.

A team of researchers from University of New Mexico School of Medicine and Cancer Research and Treatment Center, Senior Scientific, LLC, and the Center for Integrated Nanotechnologies facility at Sandia National Laboratories created nanoprobes by attaching iron-oxide magnetic particles to antibodies against HER-2, a protein overexpressed in 30% of breast cancer cases. Using these tiny protein-iron particles the team was able to distinguish between cells with HER-2 and those without, and were able to find HER-2 cancer cells in biopsies from mice. In their final test the team used a synthetic breast to determine the potential sensitivity of their system.

Dr Helen Hathaway explained, “We were able to accurately pinpoint 1 million cells at a depth of 4.5 cm. This is about 1000x fewer cells than the size at which a tumor can be felt in the breast and 100x more sensitive than mammographic x-ray imaging. While we do not expect the same level of nanoparticle uptake in the clinic, our system has an advantage in that dense breast tissue, which can mask traditional mammography results, is transparent to the low-frequency magnetic fields detected by the SQUID sensors.”

Future refining of the system could allow not only tumor to be found but to be classified according to protein expression (rather than waiting for biopsy results). This in turn could be used to predict disease progression and refine treatment plans and so improve patient survival.

La tumor registry gets $794,000 pediatric grant

JANET McCONNAUGHEY, Associated Press
Published 02:55 p.m., Monday, October 3, 2011

NEW ORLEANS (AP) — The Centers for Disease Control and Prevention is giving the Louisiana Tumor Registry a three-year, $794,000 grant to develop a system to quickly collect and report children’s cancers.

Hospitals often take six months or more to report cancer cases because they want to include information about treatment, said Dr. Vivien Chen, director of the registry at LSU Health Sciences Center New Orleans.

She said the grant will let the registry work with pathology laboratories, which diagnose cancers, and get that information within a couple of months. Regional registry workers will go to hospitals in their areas each month to get more information, she said.

Chen said the tumor registry will collaborate with state pediatric organizations and with doctors and hospitals treating children with cancer. Key partners include Lafayette, Baton Rouge and Shreveport clinics affiliated with St. Jude Research Hospital, large out-of-state children’s hospitals, and the LSUHSC-New Orleans pediatric oncology program at Children’s Hospital in New Orleans, where about half of the new pediatric cases in Louisiana are diagnosed or treated.

LSUHSC’s registry will also link to birth records, since a baby’s birth weight and any other abnormalities noted on the birth certificate, and even the parents’ ages may be linked to cancer, she said.

“As we move on, we might explore some other information. Medicare might be another thing we might link on,” she said.

This grant is the second awarded to the tumor registry since December and brings its federal support to about $3.5 million a year, according to LSU.

Scientists Work on Blood Test for Early Lung Cancer Detection

Comments Off
Posted 17 Sep 2011 — by James Street
Category Diagnostic, Lung Cancer

September 13, 2011

Jessica Berman

Scientists are developing a blood test to detect lung cancer, one of the most common and deadly cancers in the world.  The test, which looks for certain proteins in the blood, is designed to find tumors at their earliest, most treatable stage.

According to the World Health Organization, lung cancer is the leading cause of cancer death worldwide, claiming an estimated 1.5 million lives each year.  The disease is caused mainly by cigarette smoking.  Early detection followed by prompt treatment is essential to surviving this deadly, fast-growing cancer.

Researchers at the Fred Hutchinson Cancer Research Center in the northwestern U.S city of Seattle, Washington, report they have developed a new blood test for lung cancer proteins.  Those proteins are produced by tumor tissue early in the development of lung cancer and can be detected in plasma, a blood component that’s rich in proteins.

The scientists say the cancer test is so sensitive, it can detect the presence of markers or signatures that suggest tumor activity before they can be seen by advanced imaging devices such as a CT scan, which can spot tumors only a few millimeters across.

According to Sam Hanash, a scientist at Fred Hutchinson. and a lead researcher on the lung cancer blood test, using CT scans to detect tiny tumors can save the lives of patients at risk of lung cancer. But he says CT screening has a down-side: a high percentage of its images reveal nodules that appear as potentially malignant tumors.

“…That necessitate surgery, that turns out to be benign and a lot of other potential complications. So there’s a need for a blood test so that we can make CT scans more reliable,” Hanash said.

Hanash says the lung cancer blood test looks for protein signatures of the disease similar to the way other cancer blood tests work, including the CA 125 test for ovarian cancer and the prostate specific antigen, or PSA, test for prostate cancer.

In initial experiments with mice, Hanash and his colleagues discovered protein markers by switching on genes that gave the animals lung cancer, and then switching off the cancer-causing genes.

Hanash says scientists next looked to see whether they could find the same cancer protein signatures in human lung cancer cells.

“And the answer was “Yes!”  So that was pretty satisfying that in fact we’re not dealing with a curiosity type of finding that only mice seem to display, but we are dealing with a real feature of cancer cells whether mice-derived or human-derived,” Hanash said.

Hanash says researchers detected protein biomarkers unique to a number of different lung tumors, as well as some of the molecular networks of genes that drive tumor development.

He says the next step is to develop a test that doctors can use with patients at risk for lung cancer, probably in about two years.

An article describing the development of a new diagnostic test for lung cancer protein signatures is published in the journal, Cancer Cell.

Blood test to detect colon cancer gains traction, radiologists remain unconcerned

Comments Off
Posted 04 Aug 2011 — by James Street
Category Colon Cancer, CT Colonoscopy, Diagnostic
By Rebekah Moan | December 9, 2010

 

Despite the increasing popularity of blood testing for colorectal cancer, radiologists don’t have to worry CT colonography will be replaced just yet, according to experts.

A new test from Epigenomics and Warnex Medical Laboratories is infiltrating the ranks of the colon cancer screening world. On Dec. 6 the companies announced the Canadian launch of their diagnostic blood testing service. The test is derived from a blood sample and detects cell-free methylated DNA of the Septin9 gene shed into the bloodstream by colorectal tumors.

Diagnostic Imaging first reported on the Septin9 test in October. But researchers remain unconvinced Septin9 will edge out CT colonography.

“The Septin9 blood test is meant to identify colorectal cancer after it has developed and potentially already spread outside of the bowel wall,” said Dr. Judy Yee, a professor and vice chair of radiology and biomedical imaging at the University of California, San Francisco and a CT colonography expert. “It is not meant to prevent colorectal cancer.”

The purpose of CT colonography, on the other hand, is to identify precursor polyps before cancer develops, she said.

“The goals of the two tests are very different,” she said.

The Septin9 blood test may not be mature enough yet for use, according to Dr. Perry Pickhardt, a professor of radiology at the University of Wisconsin, Madison and also a CT colonography expert.

In the PRESEPT study, Septin9 detected two-thirds of colorectal cancers with a specificity of only 88%.

That means one in every three cancers would be missed, Pickhardt said.

“If this were applied to a screening population, where cancer is present in about one in every 500 adults, there would be more than 60 false-positive tests for every cancer detected,” Pickhardt said. “I don’t believe these are acceptable results, especially when you compare other noninvasive options, such as CT colonography, where the sensitivity and specificity for cancer detection is >95%.”

An attractive option might be following the Septin9 blood test with CT colonography because the risk of cancer is too low to justify colonoscopy in all cases, he said.

In any case, CT colonography remains viable in the radiology world for the detection of colon cancer.

Tumor Marker Testing Fact Sheet

Comments Off
Posted 03 Aug 2011 — by James Street
Category Biomarkers, Circulating Tumor Cells, Diagnostic, Personalized, Tumor biomarkers
By Megan McDowell | August 3, 2011

  • Tumor marker tests include a variety of tests for cancer that can be performed on cells of a tissue sample from a newly biopsied or stored tumor. Tumor marker testing provides the patient and oncologist with vital information about the tumor at the cellular level, expanding traditional pathology reports that are based on tumor size, appearance and staging of the disease.

  • Tumor markers are substances often detected in higher than normal amounts in the blood, urine or body tissues of some patients with certain types of cancer.

  • By providing insight into the genetic mechanisms driving tumor growth, tumor marker tests help guide decisions for timing and treatment choices.

  • All women diagnosed with breast cancershould have their tumors tested to help determine how their tumors will behave. Consideration should be given to repeating tumor marker tests on newly obtained tumor tissue if a woman’s breast cancer recurs after treatment. Changes that occur on a cellular level in the tumor during the course of treatment may have significant implications for disease management.

  • Women who have already had a biopsy and know they didn’t receive a tumor marker test may want to ask their physician to contact the lab where the sample was sent and request a tumor marker test be performed on the stored tissue sample.

  • Tumor marker tests are performed in the hospital’s pathologylaboratory or sent out by the hospital or oncologist to an independent laboratory. The tests use very specific techniques to reveal the presence or absence of markers such as hormone receptors for estrogen and progesterone on the surface of the cell or its nucleus.

  • Tumor marker tests include:

    -HER2 – The newest of the tests determines the presence of excessive amounts of the HER2 gene or protein. Alteration of the HER2 gene or protein in normal cells may lead to overexpression or overproduction of HER2 protein. Overexpression of HER2 contributes to an aggressive growth of the cancer and its spread to other parts of the body. HER2 overexpression occurs in 25-30 percent of women with breast cancer.

    -Estrogen Receptors (ER) – Studies have shown that estrogen, one of the female sex hormones, often regulates the growth of breast cancer. Knowledge of whether a tumor is positive or negative for the presence of estrogen receptors is used for prognosis and patient selection for anti-hormonal therapy

    -Progesterone Receptors (PR) – To help determine the response to hormonal therapy, the presence of the estrogen-regulated progesterone receptor is now determined routinely. The rate of response is much higher when estrogen and progesterone receptors are positive compared to estrogen receptors alone.

    -p53 – p53 is a tumor suppressor gene. Normally, the p53 protein, coded for by the p53 gene stops cells with DNA damage from multiplying until the DNA is repaired naturally or sends the defective cell into programmed cell death. When the p53 gene becomes damaged or mutated, the protein becomes nonfunctional and loses its checkpoint control, allowing cancerous cells to replicate more readily.

    -S-phase – In the process of cell replication, a cell cycles through a number of stages. After a cell has duplicated its genetic material and divided through the process of mitosis, it may become inactive or it can start another replicative cycle, beginning with the “S,” or synthesis phase during which genetic material duplicates again . Using a special technique, the number of cells in the S phase can be detected. A higher proportion of S phase than normal is a measure of how actively a tumor is proliferating.

  • Other tests, used primarily in research, conducted on breast cancer cells include DNA, cytometric evaluation to measure S-phase and/or DNA ploidy and tests of other genes such as Cathespin–D, CEA, and CA15–3.

  • Generally health insurance will cover tumor marker testing, however you should consult with your health insurance carrier or your physician.