Posts Tagged ‘department’

Recommendations for prostate cancer active surveillance

With active surveillance, patients undergo regular visits with prostate-specific antigen (PSA) tests and repeated prostate biopsies rather than aggressive treatment. It is distinguished from watchful waiting, in which treatment for localized disease is withheld and palliative treatment for systemic disease is initiated.

“Active surveillance is an important management option for men with low-risk prostate cancer,” says lead author Mahul Amin, MD, FCAP, Chair, Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA. “Vital to this process is the critical role pathologic parameters play in identifying appropriate candidates for active surveillance.”

Dr. Amin spearheaded the team that highlighted the pathologic parameters key for the successful identification of patients likely to succeed with active surveillance. The key parameters, at a general level, address: •Sampling, submission, and processing issues in needle biopsies used to diagnose prostate cancer •Tumor extent in needle biopsies •Biopsy reporting for all and special cases •Gleason scores, the system for grading prostate cancer tissue based on how it looks under a microscope •Precision medicine markers •Other pathologic considerations

The team further concluded that the key parameters to be reported by the surgical pathologists: 1) need to be reproducible and consistently reported and 2) highlight the importance of accurate pathology reporting.

Recommendations from the United States Preventive Services Task Force, an independent group of national experts in prevention and evidence-based medicine, and randomized trials have drawn attention to overtreatment of localized, low-risk prostate cancer. PSA screening and changing consensus on PSA testing practices are among the many factors that contribute to prostate cancer’s overdiagnosis and overtreatment.

The pathology recommendations are included in the Archives article: The Critical Role of the Pathologist in Determining Eligibility for Active Surveillance as a Management Option in Patients with Prostate Cancer: Consensus Statement with Recommendations Supported by the College of American Pathologists, International Society Of Urological Pathology, Association of Directors of Anatomic and Surgical Pathology, the New Zealand Society of Pathologists, and the Prostate Cancer Foundation.

source : http://www.sciencedaily.com/releases/2014/08/140826100651.htm

Lung cancer rarely detected by current X-ray procedures

In Norway, no other forms of cancer take as many lives as lung cancer. Each year, 2800 Norwegians develop the dreaded disease. Their prognosis is unpromising: six out of seven die within five years.

What is especially unfortunate about lung cancer is that the tumor has ample space to grow. It can thus grow for a long time before being detected.

Most patients have their first diagnosis made by X-ray imaging. Each year, Oslo University Hospital takes 30 000 chest X-rays. Nationwide, this number exceeds one million.

Nobody has ever investigated how well X-ray images function with a view to detecting lung cancer and other diseases of the chest region.

“X-ray technology has remained nearly unaltered for one hundred years,” says Trond Mogens Aaløkken at the Department of Radiology and Nuclear Medicine, Oslo University Hospital. In cooperation with a group of physicists at the Intervention Centre he has made a comparison of the proportion of patients who obtain a correct diagnosis with X-ray images and how many patients might have obtained a correct diagnosis with computer tomography (CT), which is a far more modern imaging technology.

While X-ray images are two-dimensional, CT images are three-dimensional. CT images can thus reveal the exact location of the tumor.

Too much radiation before

Until today, the radiation dose from examinations of lungs with CT has been one hundred times higher than from regular X-ray examinations. A CT scan is equivalent to five years of natural background radiation.

Radiologists have therefore been reluctant to use CT for an initial diagnosis of lung cancer.

If the X-ray examination is negative, some months may pass before the patient is referred for a CT scan. Then, it may already be too late.

“It’s sad that so many come to be treated too late because the hospitals are reluctant to use CT. The survival rate can be increased significantly if the lung cancer is initially detected by CT,” Aaløkken points out to the research magazine Apollon.

In recent years, CT scanners have become far more effective. The mathematical method for reconstructing pictures has changed completely. This means that the images now contain more information, while the radiation dose has decreased.

Little radiation now

Researchers at the Intervention Centre have now succeeded in producing CT images with the same low radiation dose as a regular X-ray image.

“We still cannot achieve the same high-quality images by replacing standard full-dose CT with ultralow-dose CT, but we have wondered whether the old low-quality X-ray examinations can be replaced by ultralow-dose CT. Although the CT dose is nearly as low as for a chest X-ray, we can obtain far more information from the images,” says associate professor Anne Catrine Trægde Martinsen, who works at the Intervention Centre and the Department of Physics, University of Oslo.

To find out what works best, the researchers have undertaken a pilot study in which they made both X-ray images and ultralow-dose CT images of a small sample of patients for whom the researchers knew the correct answer beforehand.

The radiologists who examined the images did not know what ailed the patients, but they were aware of being part of a research project, and they were told to search for all possible diseases of the chest region.

From 18 to 89 percent hits

The results were remarkable. By studying the X-ray images, the radiologists found the correct answer in only 18 percent of the cases. In other words, they missed 82 percent of the diagnoses. With ultralow-dose CT, the radiologists made a correct diagnosis in 89 percent of the cases.

“X-rays are taken out of old habit, but with X-ray the cancer is detected too late. It’s therefore smart to use ultralow-dose CT to be able to detect the disease in time,” Aaløkken states.

Moreover, with X-ray images the radiologists detected fifteen times as many false positives. A false positive means that the patient is told that he is ill, even if he is as fit as a fiddle.

“False positives are a burden on the patient. They also entail unnecessary check-ups, which incur a high cost on society,” says Aaløkken, who concludes:

With an X-ray examination, there is a high likelihood that you will not have any answer as to whether you are ill, and an answer that says that you are ill even though you are healthy. Many are diagnosed too late. This is a dramatic consequence of the fact that the health services give priority to X-ray images above CT images.

Their research caused a stir at the world’s largest medical conference for radiology, RSNA, in 2012. Their academic article was nominated as one of the ten best from the conference.

“Even though our results are extremely convincing, we need to undertake a full-scale test to be absolutely certain.”

A question of economics

Before the diagnostic procedure is changed, the researchers must calculate the cost to society.

“A CT machine costs ten times more than an X-ray machine, but it is also costly to treat patients with advanced lung cancer.

Most people believe that X-ray is a quicker procedure than CT. This is not so.

“An X-ray check takes five minutes. A low-dose CT check goes almost as quickly; it takes seven minutes. On the other hand, the radiologists need two to three times longer to interpret a CT image,” Aaløkken and Martinsen underscore.

Odd Terje Brustugun, associate professor at the Department of Oncology at Oslo University Hospital and assistant professor at the Institute of Clinical Medicine, UiO, confirms that Aaløkken and Martinsen are on the right track.

“As far as I have understood, the method can be used on existing, modern CT machines. Before it can replace ordinary chest X-ray some work needs to be done in terms of the resource situation and training of radiographers and radiologists. The method should be tested on a greater number of patients and compared to other techniques on a larger scale before we can conclude how well it works,” Brustugun points out.

source : http://www.sciencedaily.com/releases/2014/08/140825084834.htm

Cellular biology of colorectal cancer: New Insight

Lead author Kristi Neufeld, associate professor in the Department of Molecular Biosciences and co-leader of the Cancer Biology program at the KU Cancer Center, has spent the better part of her career trying to understand the various activities of APC, a protein whose functional loss is thought to initiate roughly 80 percent of all colon polyps, a precursor to colon cancer. Neufeld, along with her postdoctoral fellow Maged Zeineldin, undergraduate student Mathew Miller and veterinary pathologist Ruth Sullivan, now reports that APC found in a particular subcellular compartment, the nucleus, protects from inflammation as well as tumor development associated with chronic colitis.

Whether APC reaches the nucleus may well affect the ability of intestinal stem cells to produce differentiated cells with specialized functions, Neufeld said.

“It’s not widely appreciated, but there is still plenty of cell growth going on in adults, with the colon being a good example,” she said. “On average, we shed and replace about 70 pounds of intestinal tissue annually, so you can imagine that this process requires exquisite control to prevent tumor formation.”

Regular renewal of the colon lining occurs through stem cells that are capable of constantly dividing. These cells produce descendants that take up specific roles: By secreting mucin, for instance, goblet cells generate a mucus layer that serves as the colon’s physical barrier against its many microbial tenants. But if APC can’t find its way to the nucleus, Neufeld and her team have noted far fewer goblet cells as one outcome.

“We introduced a specific APC mutation into mice that took away the nuclear zip code, so to speak, leaving APC stuck in the cytoplasm,” Neufeld said. The researchers studied this mouse model under conditions that induce ulcerative colitis, a form of inflammatory bowel disease that can be a prelude to colon cancer.

Observing significantly more colon tumors in these mice compared to those with normal APC in the same disease setting, they hypothesized that functional nuclear APC might somehow guard against inflammation and its downstream effects, including tumor development. Now, Neufeld thinks she and her team may have a clue as to how this happens.

“The drop in goblet cell numbers we observed was striking,” she said. “We then examined one of the proteins found in mucus, called Muc2, and found that its RNA levels were greatly decreased. If there are fewer goblet cells as a result of APC being unable to reach the nucleus, there will also be less mucus, which could increase the colon’s sensitivity to bacteria and other microorganisms in the gut that are capable of promoting inflammation.”

Neufeld said while there are still no quick fixes for mutant genes, perhaps tools could be developed to synthetically replace this less-than-ideally thick mucus layer in affected people.

One known function of APC is that it halts cell proliferation: by muzzling the canonical arm of the Wnt signaling pathway, which otherwise instructs cells to go forth and multiply. Neufeld and her group have already shown, using the same mouse model, that APC stationed in the nucleus is necessary to suppress Wnt and its signaling partners — particularly β-catenin, a key target of normal APC. With a role for nuclear APC in controlling goblet cell differentiation now supported, the researchers are probing possible mechanisms to learn if and how Wnt pathway members might be involved.

Comprising 2,843 amino acids, APC is a large protein.

“Rather than being a simple, single-function protein, APC is more like a complex set of moving parts, each doing something different and most still poorly understood,” Neufeld said. “I think if the sole purpose of this protein was to target β-catenin for destruction, it wouldn’t need to be this large. Our next job is to figure out exactly how goblet cell differentiation is controlled by one or more of APC’s many components.”

Beyond a slew of mechanistic details, the bigger picture that Neufeld and her group will keep exploring is that some colon cancers could arise from an inflammatory response to bacterial penetration of a thinner-than-normal mucus layer in the gut, resulting from defective APC. The possibilities of just what APC does and doesn’t do, and how to compensate for any intestinal glitches related to loss of APC function, present a challenging mystery but also a plentiful harvest for scientists like Neufeld to reap going forward.

source : http://www.sciencedaily.com/releases/2014/08/140821102433.htm