Smoking is a risk factor in the clear cell and papillary subtypes of renal cell carcinoma (RCC), but not in chromophobe RCC, according to a study published in The Journal of Urology.

Neel Patel, MD, and fellow researchers from the Roswell Park Cancer Institute in Buffalo, NY, collected smoking data and retrospectively assessed 816 patients with nonfamilial RCC or benign pathology who had undergone nephrectomy at a National Comprehensive Cancer Network treatment center, seeking to find an association with histological diagnosis.

Among those patients, 21% were active smokers and 30% were former smokers.

Active smoking was found to be more common among those with clear cell (23 percent) or papillary (26 percent) RCC compared to those with benign histology (14 percent each) or chromophobe RCC (6 percent).

Smoking history – both active and former – was generally found to be uncommon in chromophobe RCC (26 percent) compared to clear cell (53 percent) or papillary (58 percent). In addition, smoking extent based on mean pack-years was significantly lower in chromophobe RCC (9.4 mean pack-years) compared to clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years).

Upon propensity analyses, both clear cell and papillary RCC were found to be independently associated with active smoking, but not chromophobe RCC.

“These findings underscore distinct carcinogenic mechanisms underlying the various RCC subtypes,” the authors concluded.

Reference

1. Patel NH, Attwood KM, Hanzly M, et al. Comparative analysis of smoking as a risk factor among renal cell carcinoma histological subtypes. 2015. The Journal of Urology. [online ahead of print]. doi: 10.1016/j.juro.2015.03.125. 

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Editor’s Note: This is the third in a series of articles exploring partnerships between basic scientists and clinicians supported by the Duke CTSA through the Duke Translational Research Institute (DTRI) Collaborative Pilot Agreements.

People with end-stage kidney failure depend for their very life on connecting their bloodstream to a dialysis machine several times a week. Each time, all of the blood is pumped out of the body and into a blood-cleansing machine that filters the blood before circulating it back into their body over a period of about four hours. The success of this life-saving procedure depends on a hollow tube implanted under the skin—an arteriovenous graft—which provides ready access to the bloodstream.

The Bullt Proof graft includes two
penetration-resistant chambers to
eliminate needles neadlessly damaging
the soft tubing used in dialysis. 

But, as Roberto Manson, a researcher in Duke’s Department of Surgery, explains, the hollow tube that allows the procedure has a big problem. Needle pokes.

The problem with standard grafts is that manufacturers make them primarily to ensure a strong blood flow through the conduit. They aren’t made to withstand the regular needle pokes that dialysis requires. It’s very easy for dialysis professionals to inadvertently poke the needle straight through one side of the graft and out the other. As a result, patients on dialysis often suffer painful bruising and infections from arteriovenous graft injuries and related complications.

After studying the problem, Manson and his teammates have an answer. Poke-proof grafts with self-sealing capabilities.

With funding from the Duke CTSA through the Duke Translational Research Institute (DTRI) Collaborative Pilot Award, Manson, Duke vascular surgeon Jeffrey Lawson, and senior vascular physician assistant Shawn Gage aim to get this game-changing medical device out to patients within a year. Gage, co-inventor and lead developer of the technology, has been working with a local engineering and design firm, Gilero Biomedical, to conceptualize and create this immediate use, error proof, dialysis graft.

Lawson and Gage spend a good part of their time in the operating room implanting new grafts and correcting those that have failed. In a conference room on the fourth floor of Duke’s Medical Sciences Research Building, Lawson flips through a series of gruesome images on his computer screen that illustrate just how miserable graft failures are for kidney disease patients. It’s also costly. Arteriovenous graft injuries and complications are responsible for millions of dollars in health care expenditures every year.

“It costs $50,000 every time this happens,” Lawson said. “It’s expensive, painful, and I think unnecessary.”

That line of thinking has led Lawson and others to search for solutions. “That’s the nature of invention,” Lawson said. “You get sick of something failing over and over again and you think there has to be a better way to do this.”

Lawson, Manson and Gage hold the latest
 prototype of the "Bullet Proof" graft. 
Photo by Marsha A. Green, DTMI

Lawson, Manson, and Gage, appear to have found that better way.

Their device, called Bullet Proof ™, is surprisingly simple. Over most of its length, their new graft is identical to those that are standardly used. But Bullet Proof has two penetration-resistant chambers—one for the needle that sends blood out of the body and the other for the needle that sends the blood back in again—each built with a window of material that seals itself after each needle poke. Along the back of the tube is a rigid plate that makes it impossible for a needle to go straight through the graft. Lawson likes to illustrate this by pushing a needle in and showing how it bends rather than poking through.

The Duke team has already fabricated simple prototypes of their new device and launched a company called InnAVasc (http://innavasc.com) with the goal to develop their graft into a marketable product. With funding from the Duke CTSA through the Duke Translational Research Institute (DTRI) Collaborative Pilot Award, they are working to finalize their device design and conduct tests of Bullet Proof to further demonstrate the puncture resistant and self-sealing capabilities in the laboratory.

The investigators are implanting the grafts into pigs to see how well they really work in a living, breathing animal. After a poke of a standard graft, there is considerable bleeding. Dialysis professionals typically must apply pressure for some time before the bleeding stops. In animal tests, it appears as though Bullet Proof grafts result in little more than a trickle of blood as their walls seal themselves back up. As a result, the tissue around a Bullet Proof graft doesn’t show the inflammation and injury that’s typical in dialysis patients today.

In animal tests, it appears as though Bullet Proof grafts result in little more than a trickle of blood as their walls seal themselves back up. As a result, the tissue around a Bullet Proof graft doesn’t show the inflammation and injury that’s typical in dialysis patients today.

The Bullet Proof concept and device is getting great reviews. In April, the Duke team won the CX Innovation Showcase held in London, which is dedicated to vascular and endovascular innovation. Manson and Lawson say they’ve already spoken with the FDA and are working on a package to present to them in hopes of testing the new device in patients as soon as possible. If they can secure enough funding to proceed to a final, medical-grade product, they hope to begin implanting the first Bullet Proof grafts into people within a year.

That’s promising news for dialysis patients and for the doctors and nurses who care for them. Gage says that Bullet Proof might even enable some patients to begin undergoing dialysis in the comfort of their own homes.

“We think this can save the health system money and patients from misery,” Lawson said. “The idea just makes common sense and the DTRI award is important in providing financial support to push it forward.”

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