Routine Colonoscopies Save Lives

March is Colorectal Cancer Awareness Month

Newswise, March 3, 2016 — Stan Quinn’s routine colonoscopy may have saved his life.

When Mr. Quinn, 57, became a new patient at Loyola University Health System last year, his physician prescribed a routine colonoscopy to catch him up on preventive health recommendations.

“I didn’t think anything of it, just that it was a routine exam that was going to reveal nothing wrong,” said Mr. Quinn, who was not experiencing any health problems. “What they actually found was a mass that was too big to remove during the colonoscopy.”

March is Colorectal Cancer Awareness Month and the message is simple: this disease is highly preventable. Colorectal cancer is 100 percent preventable through screenings that detect and remove small, pre-cancerous growths called polyps.

Loyola staff will raise awareness for the prevention of colon cancer by wearing blue next Friday, March 4, in support of National Dress in Blue Day™.

Cancer of the colon or rectum is the second leading cause of cancer deaths among both men and women in the United States. According to the Centers for Disease Control and Prevention, about 140,000 Americans are diagnosed annually with colorectal cancer, and more than 50,000 people die from it.

“Colorectal cancer really should get the same attention as breast cancer, prostate cancer and skin cancer,” said Theodore Saclarides, MD, division director of colorectal surgery at Loyola. “Regular screenings really do save lives.”

“It is now clear that not every colonoscopy is equal,” says Neil Gupta, MD, co-director of the digestive health program and director of interventional endoscopy at Loyola. “Once you’ve decided it’s time to get a screening colonoscopy, the next step is to make sure that you get a high quality one.”

Loyola offers all of the colorectal cancer screening tests that are recommended by the United States Preventive Services Task Force and national medical societies. There are two types of colorectal cancer screening tests: tests that detect colorectal cancer and tests that can detect both colorectal cancer and pre-cancerous polyps, Dr. Gupta said. Colonoscopy, CT colonography (virtual colonoscopy), and flexible sigmoidoscopy are all screening tests that can detect colorectal cancer and pre-cancerous polyps.

Stool tests for blood or DNA (such as fecal occult blood test, fecal immunochemical test, or cologuard) are designed to detect colorectal cancer only.

Get checked, Dr. Saclarides advises, if:

You have a change in bowel habits.

You reach an age at which a colonoscopy is recommended. Current guidelines recommend that everyone get screened for colorectal cancer starting at the age of 50.

Your lifestyle and family history predispose you to colon cancer. People with a family history of colorectal cancer or polyps, people with inflammatory bowel disease (such as Crohn’s disease or Ulcerative colitis), and people with hereditary cancer syndromes should start screening earlier.

Loyola physicians perform high quality colonoscopies, performing consistently above the national average on colonoscopy quality measures, including being able to examine the entire colon (cecal intubation rate), having a good bowel prep during the colonoscopy, and detection of pre-cancerous polyps (adenoma detection rate).

“The higher your physician’s adenoma detection rate, the less chance you have of developing colon cancer after your colonoscopy,” said Dr. Gupta, who has an adenoma detection rate of more than 50 percent, meaning he has removed pre-cancerous polyps in more than 50 percent of the screening colonoscopies he has performed. “An adenoma detection rate of at least 20 percent is currently considered a minimum benchmark.”

In addition to the clinic, Loyola treats patients at the GI cancer risk assessment program, where gastroenterologists and geneticists examine and assign a risk to concerned patients.

After Mr. Quinn’s colonoscopy, a biopsy revealed the tumor might be early cancer so the mass had to be removed quickly. Mr. Quinn was referred immediately to Dr. Saclarides, who removed a portion of the colon through laparoscopic surgery, a less-invasive technique involving a small incision, less blood loss and a faster recovery time.

“Stan is basically cured,” Dr. Saclarides said. “And it is all thanks to his getting a colonoscopy, his physicians recommending him to a colorectal surgeon and his being compliant and following through with the procedure.”

Randomized Trials Network Collaborative Research Group.

The National Institutes of Health funded research efforts critical to the study.

Common Blood Test Could Predict Risk of 2nd Stroke

Elevated levels of enzyme linked to increased likelihood of ischemic stroke

Newswise, March 3, 2016 — A new discovery about ischemic stroke may allow to doctors to predict a patient’s risk of having a second stroke using a commonly performed blood test and their genetic profile.

The researchers have linked high levels of C-Reactive Protein, an enzyme found in the blood, with increased risk for recurrent ischemic stroke. C-Reactive Protein (CRP) is produced in the liver in response to inflammation, and it is already checked to measure people’s risk of developing coronary artery disease. 

The new research suggests it could be a useful tool for ischemic stroke patients as well.

“The biggest risk of death for someone who has already had a stroke is to have another one,” said University of Virginia School of Medicine researcher Stephen Williams, PhD. “So it’s really important to be able to try and target those individuals who are at the highest risk for the thing that very well may kill them.”

Ischemic Stroke Risk

Ischemic strokes result from blockages preventing blood flow to the brain; they are responsible for approximately 85 percent of all stroke cases. (Hemorrhagic strokes, on the other hand, occur when blood vessels burst and bleed into the brain.)

To better understand ischemic stroke, Williams and his colleagues set out to determine how our genes affect the levels of biomarkers such as CRP in our blood. Not only did they find that elevated CRP levels suggest increased stroke risk, they identified gene variations that drive those risks.

“So we have the genetics influencing [CRP] levels, which then increases the risk of having a recurrent stroke. Then we went back and said alright, can we predict the increased risk purely based on the genetics, which we were able to do,” Williams said.

“There’s this shared genetic susceptibility not only for increased C-Reactive Protein but for increased risk for stroke. We could estimate what’s called a hazard ratio – basically the increased risk for having or not having a second stroke – based on the genetics.”

Williams envisions a day when doctors might focus on CRP levels and a patient’s genetic makeup to determine their overall risk for a second stroke. But even CRP levels alone could be a useful tool in assessing risk after the initial stroke.

“Getting a CRP measure on someone is really simple. It’s just a blood draw. You don’t have to take something like a biopsy which patients might have an aversion to,” Williams said. “It’s not very expensive, and it’s part of routine workups that could be done for patients. However, combined with genetic information we may have even more power to identify those at greatest risk.”

Findings Published
The findings have been published online by the scientific journal Neurology in an article written by Williams, Fang-Chi Hsu, Keith L. Keene, Wei-Min Chen, Sarah Nelson, Andrew M. Southerland, Ebony B. Madden, Bruce Coull, Stephanie M. Gogarten, Karen L. Furie, Godfrey Dzhivhuho, Joe L. Rowles, Prachi Mehndiratta, Rainer Malik, Josée Dupuis, Honghuang Lin, Sudha Seshadri, Stephen S. Rich, Michèle M. Sale 

Stroke Risk Increases From Stenting in Older Patients

Newswise, February 21, 2016 – Vascular surgery appears to be safer than stenting for patients over 70 years of age with carotid stenosis, or a blockage of the carotid arteries in the neck, according to new findings published today in the Lancet.

The international study, led by investigators at the University of Alabama at Birmingham, looked at the two standard methods for treating plaque buildup in the carotid arteries: a surgical procedure called carotid endarterectomy against carotid artery stenting.

The surgical procedure, or CEA, involves surgeons’ opening up the artery to remove plaque. It is an invasive surgery first done in 1946.

Stenting is a newer, less invasive procedure in which a catheter is threaded through blood vessels, usually from the groin, to the affected area in the artery. A balloon is used to open the blocked artery, and a mesh stent is placed to hold it open.

“Stenting was hailed as a less invasive alternative to surgery, one that avoided many of the hazards and risks inherent in a surgical procedure,” said George Howard, Dr.P.H., professor in the Department of Biostatistics in the UAB School of Public Health and the study’s first author.

“What we find, however, is that the risk of stroke in patients over the age of 70 is twice that with stenting than with the surgical CEA procedure.”

The study looked at data from four randomized controlled trials within the Carotid Stenosis Trialists’ Collaboration with patients with symptomatic carotid stenosis. Collectively, 4,754 patients were followed. Age was not associated with increased stroke risk for either surgery or stenting in patients under age 70; but stent patients over 70 had an increased risk, particularly in the immediate time frame of the procedure.

“These findings are very conclusive — stenting has a higher risk for stroke over carotid surgery in the older patient, older than 70,” Howard said. “This study should help drive decision-making and establish appropriate practice guidelines in the treatment of carotid stenosis.”

Howard says the stenting procedure itself seems to be causing the increased risk.

“The risk appears centered on the periprocedural period, the time during and immediately after the procedure,” Howard said. “The risk does not appear to continue in the months or years following the procedure.”

Howard acknowledges that advances in stenting, such as the routine use of closed-cell stents, which seem to be associated with lower rates of procedural stroke and the development of novel protection systems, might allow safe stenting for elderly people in the future.

“But for now, stenting in an older population needs to be done with great caution,” he said.

In addition to investigators at UAB, the international study included investigators from Cardiovascular Associates of the Southeast, Birmingham, Alabama; Clinic for Radiology and Neuroradiology, UKSH Campus Kiel, Kiel, Germany; Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands; Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, U.K.; Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria; Department of Vascular and Endovascular Surgery, Vascular Center, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany; Department of Neurology, Hôpital Sainte-Anne, Université Paris-Descartes, DHU Neurovasc Sorbonne Paris Cité, INSERM U894, Paris, France; Clinical Trial Service Unit and Epidemiological Studies Unit, Oxford University, Oxford, U.K.; Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, U.K.; and Department of Vascular Surgery, University of Paris, XII, Hôpital Henri Mondor, Paris.

New Predictor of Cancer

When your biological age is older than your chronological age, the risk of getting and dying of cancer rises

Newswise, February 21, 2016 --- Epigenetic age is a new way to measure your biological age. When your biological (epigenetic) age is older than your chronological age, you are at increased risk for getting and dying of cancer, reports a new Northwestern Medicine study.

And the bigger the difference between the two ages, the higher your risk of dying of cancer.

“This could become a new early warning sign of cancer,” said senior author Dr. Lifang Hou, who led the study. “The discrepancy between the two ages appears to be a promising tool that could be used to develop an early detection blood test for cancer.”

Hou is chief of cancer epidemiology and prevention in preventive medicine at Northwestern University Feinberg School of Medicine and co-leader of the cancer prevention program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

“People who are healthy have a very small difference between their epigenetic/biological age and chronological age,” Hou said. “People who develop cancer have a large difference and people who die from cancer have a difference even larger than that. Our evidence showed a clear trend.”

A person’s epigenetic age is calculated based on an algorithm measuring 71 blood DNA methylation markers that could be modified by a person’s environment, including environmental chemicals, obesity, exercise and diet. 

This test is not commercially available but is currently being studied by academic researchers, including a team at Northwestern.

In DNA methylation, a cluster of molecules attaches to a gene and makes the gene more or less receptive to biochemical signals from the body. The gene itself -- your DNA code -- does not change.

This is the first study to link the discrepancy between epigenetic age and chronological age with both cancer development and cancer death using multiple blood samples collected over time. 

The multiple samples, which showed changing epigenetic age, allowed for more precise measurements of epigenetic age and its relationship to cancer risk. Other studies have looked at blood samples collected only at a single time point.

The final paper was published Feb. 15 in EBioMedicine. 

The study was a longitudinal design with multiple blood samples collected from 1999 to 2013. Scientists used 834 blood samples collected from 442 participants who were free of cancer at the time of the blood draw.

For each one-year increase in the discrepancy between chronological and epigenetic ages, there was a 6 percent increased risk of getting cancer within three years and a 17 percent increased risk of cancer death within five years. Those who will develop cancer have an epigenetic age about six months older than their chronological age; those who will die of cancer are about 2.2 years older, the study found.

“Our results suggest future researchers should focus on the epigenetic-chronological age discrepancy for its potential to show a big picture snapshot of human health and disease at a molecular level,” said first author Yinan Zheng, a predoctoral fellow at Feinberg.

Northwestern scientists now are studying whether individuals can lower their epigenetic age through lifestyle improvements such as increasing exercise and having a healthier diet, noted Brian Joyce, co-first author and predoctoral fellow at Feinberg. 

The study is titled “Blood Epigenetic Age may Predict Cancer Incidence and Mortality.” 

The research was funded by the Epidemiology Research and Information Center, U.S. Department of Veterans Affairs grant NIEHS R01-ES015172. Additional funding support was provided by the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund.

A Shot in the Arm for Flu Vaccine Distribution

Newswise, February 19, 2016— Each fall, doctors stress the importance of getting a flu shot: influenza is the most frequent cause of death from a vaccine-preventable disease in the United States. But on-time delivery of the vaccine can be tenuous, and there can be shortages during times of peak demand, as seen in 2014.

Research co-authored by Fuqiang Zhang, professor of operations and manufacturing management at Washington University in St. Louis’ Olin Business School, proposes a new contract scheme for the vaccine supply chain that could reduce patient wait time.

“In the past, we have seen major flu vaccine shortages during the vaccination season, even though the total supply for the flu vaccines was abundant,” Zhang said. “The major reason for this is because of late delivery.”

The process begins months in advance of influenza season. Starting in January, manufacturers make educated guesses about what flu strains the federal government will target and start production of a vaccine to match. They try to make a large quantity that will be ready to sell to retailers by vaccination season, which usually runs from late September to mid-November.

The U.S. Food and Drug Administration makes its vaccine recommendation in February or March. If manufacturers have guessed incorrectly on any of the strains, they must restart that part of production.

Retailers, aware of the manufacturers’ risk, anticipate potential delay in shipments and may commit to smaller orders to avoid requesting a large supply that could arrive in late fall, when public demand will be down, and then being left with unused doses. The manufacturers, knowing that retailers will be cautious, are reluctant to produce a large amount before the FDA’s final announcement.

The manufacturer-retail gap is called a negative feedback loop. The result can be a shortage during the period of peak demand, as happened in 2014.

“Two parties are making their own decisions, but they are dependent on each other,” Zhang said. “When you have a decentralized supply chain with independent parties and they are self-interested, they may not want to make decisions that are optimal for the entire supply chain. They will make decisions that maximize their own payoff or profit.

“That’s a key issue behind this flu vaccine shortage problem,” he said

.

Zhang teamed with Tinglong Dai of Johns Hopkins University and Soo-Haeng Cho from Carnegie Mellon University and examined the current supply chain process from start to finish.

In the research, recently accepted by the journal Manufacturing & Service Operations Management, Zhang and his partners propose a new solution called a Buyback and Late Rebate (BLR) contract.

Both buybacks (returns for time sensitive products) and rebates on late shipments have been used separately in an attempt to alleviate the flu vaccine negative feedback loop, with limited success. Zhang said the combined incentive approach will make a big difference in fixing the supply chain gaps.

“If you use buyback and late rebate separately, they don’t solve the whole problem,” Zhang said. “We found that combining these two incentive contract terms, we optimize the supply chain’s performance and maximize its efficiency.”

Zhang and his co-authors believe that the combination of 100-percent buyback and rebates on late shipments would motivate retailers to commit to larger orders, which in turn would lead manufacturers to commit to greater and more prompt production. The negative feedback loop would be broken, and a steady, reliable flow of vaccine would be available, to the benefit of manufacturers, retailers, and patients.

“We looked at incentive issues for the different parties, and then tried to provide a holistic solution to the problem,” Zhang said.

Majority of Patients with Locally Advanced Head and Neck Cancers Use Life-Altering Strategies to Cope with Cost of Treatment

Study also finds perceived social isolation affects health care utilization

Newswise, February 19, 2016—The majority of patients with locally advanced head and neck cancers (LAHNC) rely on cost-coping strategies that alter their lifestyle in order to manage the financial burden of their care, according to research presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

Researchers also identified perceived social isolation, or a lack of social support coupled with increased loneliness, as a risk factor for sub-optimal medication adherence and health care utilization during treatment for LAHNC.

Treatment for locally advanced head and neck cancers -- diseases marked by high morbidity and high treatment costs -- is very intense, often combining surgery, radiation therapy and chemotherapy.

Moreover, treatment often causes social side effects, such as an increased financial toxicity or financial burden, in addition to physical side effects.

This study examined factors associated with these social side effects by following patients diagnosed with head and neck cancer over six months to assess how they coped with the cost of their cancer treatment as well as whether perceived social isolation, or the lack of social support, was a barrier to their care.

This prospective longitudinal study collected six monthly lifestyle surveys from 73 patients with treatment-naive LAHNC who were diagnosed at a single, high volume institution between May 2013 and November 2014.

The survey assessed the use of several lifestyle-altering financial coping strategies, as well as out-of-pocket costs, loss of productivity, compliance with their medication regimen, and health care utilization (specifically, inpatient length of hospital stays and number of missed appointments).

Researchers also measured patients’ demographics, health insurance status, wealth, household income and type of tumor. Perceived social isolation was evaluated prior to treatment for each patient.

Most patients in the study were male (78 percent), Caucasian (74 percent) and covered by private health insurance (54.8 percent).

Multivariable regression modeling was used to assess the influence of patient characteristics on the use of cost-coping strategies and perceived social isolation.

More than two thirds (69 percent) of the LAHNC patients reported relying on one or more lifestyle-altering cost-coping strategy while managing their cancer.

The most common strategy was spending savings (62 percent), followed by borrowing money (42 percent), selling possessions (25 percent) and having family members work more hours (23 percent).

Socioeconomic factors were associated with reliance on cost-coping strategies. Patients with Medicaid used more financial coping strategies compared to patients with private insurance (Odds Ratio (OR), 42.3; p = 0.005).

In addition, increased out-of-pocket costs and decreased wealth were independently associated with the use of cost-coping strategies (p < 0.01).

“Physical side effects are not the only ones our patients endure,” said Sunny Kung, a second-year medical student at the University of Chicago Pritzker School of Medicine and lead author on the study.

 ”Our findings indicate that the majority of our patients have adopted or will adopt strategies to cope with the financial side effects of their care.”

The study also examined prevalence of perceived social isolation among LAHNC patients and its association with socioeconomic factors and health care utilization. 

Clot-Busting Therapy Reduces Mortality in Deadliest Form of Stroke

Phase-3 clinical trial results demonstrate first effective treatment for severe type of bleeding stroke

Newswise, February 19, 2016 — The use of clot-busting drugs to clear blood from the brain’s ventricles may be the first effective strategy to decrease mortality for a type of catastrophic bleeding stroke, according to phase-3 clinical trial results announced Thursday at the International Stroke Conference in Los Angeles.

The treatment also significantly reduced post-stroke disability in a subset of patients, according to data presented by trial leaders from Johns Hopkins University and the University of Chicago.

“Hemorrhage in the brain used to be an essentially untreatable condition, but we now have hope with a therapy that may be effective at saving lives,” said Issam Awad, MD, John Harper Seeley Professor of Surgery at the University of Chicago Medicine, who was co-chair and surgical director for the CLEAR III clinical trial.

CLEAR III tested the benefits of the clot-busting drug alteplase, also known as tPA, in improving outcomes for intraventricular hemorrhage. In this particularly severe form of stroke, blood pools and clots in the brain’s ventricles—cavities that normally hold cerebrospinal fluid.

The randomized, double-blinded and controlled trial enrolled 500 patients from 73 clinical sites around the world. Every patient received either tPA or saline through a brain catheter, and were otherwise treated by current standards of critical care.

Researchers found that swift application of tPA directly into the ventricle, combined with a drainage catheter, reduced overall death rates by 10 percent, or about a third relative to death rates in the saline group.

Treatment with tPA almost doubled the likelihood of good functional recovery in patients with high volume bleeds who had most of the blood removed. Patients with smaller clots did not benefit, but no adverse side effects were observed when compared to the control group.

“For many patients, this approach can significantly reduce disability after a stroke, and can be the difference between going home instead of going to a nursing home,” Awad said.

Hemorrhagic strokes are triggered by ruptured blood vessels that leak blood into the brain, increasing intracranial pressure and causing severe damage to brain tissues.

Accumulated blood quickly clots and is difficult to remove even by open brain surgery. Around 15 percent of strokes are hemorrhagic, but they account for roughly 40 percent of all stroke deaths.

Nearly half of these bleeding strokes involve some degree of intraventricular hemorrhage (IVH), a complication where blood pools in the ventricles. IVH can be particularly catastrophic, with an estimated mortality rate between 60 and 80 percent. Among those who survive, as many as 90 percent become severely disabled.

An international effort

Early studies suggested tPA, an FDA-approved clot buster for conditions such as heart attacks and non-bleeding strokes, might be effective in removing accumulated blood and alleviating its damaging effects after a hemorrhagic stroke. To study the feasibility of this approach, a phase-2 clinical trial (CLEAR-IVH), initially tested tPA in a small group of IVH patients.

After patients were stabilized, tPA was administered directly into the ventricle through an external, surgically placed catheter. The patients received the tPA for three days and a catheter continually drained blood until the ventricle cleared.

The study confirmed the safety and efficacy of the procedure, and supported the need for a large-scale phase-3 trial.

CLEAR III, which was overseen by Awad and Daniel Hanley Jr., MD, the Harriett Legum Professor of Acute Care Neurology at Johns Hopkins Medicine, began in 2009 and was completed in 2015. Roughly half of the 500 enrolled patients received tPA and the other half received saline.

Both groups had extraventricular drains and were treated by the current best standards for critical care. All patients were monitored remotely to maintain consistent treatment across centers, which could vary greatly in facilities, staff and languages. Data analysis and overall trial oversight was provided by the Johns Hopkins team.

To ensure safety and accurate catheter placement, surgical oversight was provided by Awad and his staff at the University of Chicago Medicine, which served as the surgical center for the trial. Before tPA could be given, images of catheter placement for every patient had to be sent to and analyzed by the UChicago team, who were on call 24/7 throughout the five-year trial.

“We had to verify that all the criteria were met in order to deploy that treatment safely,” Awad said. “Every single patient was monitored in real time, often over an iPad or iPhone, to make sure the drug reached the right part of the brain.”

Immediate impact

The results of CLEAR III show tPA treatment significantly decreases mortality in one of the worst forms of hemorrhagic stroke. Analyses led by Awad and his team revealed the most important factor in improving functional recovery was the volume of blood removed.

The likelihood of a good outcome in patients with larger clots, defined as greater than 20 mL of pooled blood, improved by nearly 20 percent. The more blood that was cleared, the greater the odds were of reduced disability—rising to nearly double in patients who had 90 percent of their clots removed.

Patients who received additional doses of tPA and had multiple drainage catheters inserted had higher clot removal. In patients who started with less than 20 mL of blood in the ventricles, no benefits were observed.

“Outside our study this drainage was only used in 8 percent of hemorrhagic stroke cases, and we showed this technique can really make a difference,” Hanley said. “Our results suggest that physicians should begin to think about routinely using it for stable hemorrhagic stroke patients.”

CLEAR III data now support the use of tPA and a ventricular drain as the most effective treatment for patients with high volume IVH strokes.

Awad notes that, if possible, these patients should be treated at comprehensive stroke centers, which have access to neurosurgeons, neurocritical care specialists and other resources for severe strokes. The CLEAR III team is now implementing an educational strategy on how to manage IVH with tPA at comprehensive stroke centers around the U.S.

“When we entered into the trial, we knew very little about how this therapy ought to be used, in whom it should be used, and whether it was safe,” Awad said.

“We now have clear data on how best to implement the procedure, and for at least a group of patients, we know it can nearly double the likelihood of a favorable outcome.”

A sister clinical trial, MISTIE, co-led by Awad and Hanley, is currently underway to test the safety and efficacy of tPA as a treatment for patients with hemorrhagic strokes in which bleeding occurs in brain tissue but does not leak into the ventricles. Patients for that study are currently being enrolled.

CLEAR III was supported by the National Institute of Neurological Disorders and Stroke (5U01 NS062851) and Genentech.

For more information, visit www.braininjuryoutcomes.com/clear-about and www.uchospitals.edu/specialties/neurosciences/stroke-neurovascular/stroke.html