Showing posts with label Toronto XVIVO Lung Perfusion System. Show all posts
Showing posts with label Toronto XVIVO Lung Perfusion System. Show all posts

Thursday, June 27, 2013

Toronto XVIVO Perfusion System boosts lung donor pool

As we approach the July 1st Canada Day weekend we remember to celebrate the blessings and bounties our Nation has given us. For me its the new life I was given by a lung transplant eleven years ago, thanks to my donor and Dr. Shaf Keshavjee, at Toronto General Hospital. This recent article in The Toronto Star highlights his achievements.


Toronto lung transplant surgeon leading innovations to boost donor organ pool


“I think the impact of this will be changing the 15 per cent world utilization (for donated lungs) to 50 per cent. That is more than tripling the number of lung transplants done around the world,” Keshavjee says. “This came from here and it’s going to impact the world.”

By:  Health, 

The Toronto Star

Toronto surgeon Dr. Shaf Keshavjee’s innovations are transforming how lung transplants are done. He has lead the development of the Toronto XVIVO Perfusion System, which treats and improves high-risk donor lungs so they can be safely used for transplant.


Dr. Shaf Keshavjee, seen in the hall of Toronto General Hospital immediately after he performed a double-lung transplant in February, has received the Order of Ontario for his innovative work in his field.

Dr. Shaf Keshavjee, seen in the hall of Toronto General Hospital immediately after he performed a double-lung transplant in February, has received the Order of Ontario for his innovative work in his field.

Dr. Shaf Keshavjee apologizes as his BlackBerry keeps buzzing. He is receiving emails from the Trillium Gift of Life Network, Ontario’s organ and tissue donation agency.
They are offering him a pair of lungs — organs from an individual whose identity must be kept secret for ethical reasons, and likely the victim of a recent accident, head injury or brain hemorrhage — from some undisclosed location in Canada.
Keshavjee, director of the Lung Transplant Program at Toronto General Hospital, part of the University Health Network, peers closely at the screen of the mobile device. He is looking at an x-ray of the organs. The image is tiny, but to his trained eye, he can tell the organs are less than perfect.
“There is some abnormality because there is some lightness to it,” he says, pointing to a couple of minuscule white dots.
The lungs are the most fragile of all the organs and injuries to this pair may have been sustained during whatever tragedy led to the donor’s brain death. Or after, when resuscitation attempts were made. Or even after that, when the body was kept alive on life support.
Typically, such damaged lungs would not be considered for transplant. Indeed, an average of only 15 per cent of donated lungs end up being used worldwide.
But because of innovations led by Keshavjee, Toronto General is now able to use 40 per cent of the lungs offered. And Keshavjee is working to raise that number.
For his efforts, he was recently recognized with the Order of Ontario and two Queen’s Jubilee medals. His accomplishments are indeed an Ontario success story. His innovations are transforming lung transplant surgery around the world.
Keshavjee types a response on his BlackBerry, telling Trillium he will take the lungs.
“Smartphones have made it a lot easier. I can do this lying in my bed in the middle of the night. And I do,” he says.
So begins the complex process that will ultimately lead to someone who is dying of lung disease getting a transplant.
There are more than 80 Ontarians waiting for either a lung or a heart-lung transplant. About 20 per cent of them will die on the waiting list.
For Keshavjee, who has done about 400 lung transplants, this is just another day at the office.
“I will have a recipient ready tonight at midnight to start fitting the lungs in,” says the 51-year-old transplant surgeon who is now planning to work into the next day.
This is only one of Keshavjee’s jobs. He is also surgeon-in-chief at the University Health Network, a researcher, medical school professor and thoracic surgeon who does elective surgery, mostly on lung cancer patients.
His biggest claim to fame is leading the development of the Toronto XVIVO Perfusion System (ex vivo means outside the body), which treats and improves high-risk donor lungs so they can be safely used for transplant.
A couple of weeks after the initial interview, Keshavjee allows a reporter and photographer to tag along to see how the system works.
A pair of lungs arrives at the hospital in a blue Coleman cooler at 10:30 a.m. on a Monday. They were harvested from an anonymous donor’s body, somewhere in Canada, six hours earlier.
While a family somewhere in Canada grieves for the loss of the donor, a man in his 60s with advanced chronic obstructive pulmonary disease is being prepped for transplant surgery. He’s excited and jittery, too nervous to be interviewed by a reporter.
Besides, it’s difficult to talk. He needs 100 per cent oxygen at all times just to stay alive.
At this point, it’s not certain whether the transplant will even go ahead. The donor lungs are in bad shape, inflamed and full of fluid.
The lungs arrive in operating room 18, the organ regeneration laboratory, on the second floor of the hospital. A team of about six medical professionals is already assembled. They include surgeons, nurses and perfusion specialists who operate the XVIVO system.
There are also research fellows from Hong Kong, Chile, Spain and Brazil. Professionals from every major transplant center around the world have come through the hospital to learn the technique.
The lungs are removed from the cooler and placed into a bucket of ice. A tube is attached to the pulmonary artery, which normally delivers blood to the lung from the heart. Another tube is sewn to a vein that normally drains blood out of the lung.
The organs are then moved to a steel table in the center  of the room atop of which sits the XVIVO device. Also known as “the bubble,” it resembles a glass-domed cake plate.
Here, the lungs are hooked up to a circuit that includes a ventilator and heart-lung machine, which pumps a preservation solution into them. The solution, made of low-potassium dextran, was initially developed by Keshavjee and later perfected by others.
As the lungs are brought back up to body temperature, they are healed with a type of anti-inflammatory therapy, also developed by Keshavjee, which makes them less prone to malfunction.
Like something out of a science fiction novel, the lungs eventually begin inflating and deflating. The disembodied organs are alive, breathing on their own.
“It’s something I wouldn’t have imagined seeing in my lifetime,” says Keshavjee, who still marvels at the accomplishment.
Keshavjee bustles around the hospital while the lungs recover on the XVIVO system. He has a couple of meetings, a clinic with cancer patients and an interview with a candidate for a nurse navigator position.
He continuously checks on the lungs, calling the OR, visiting in person and even checking in via Skype on an iPad.
The XVIVO team updates him with results of ongoing tests. They assess the lungs’ function with blood gases, x-rays and bronchoscopies. They check the resistance to the flow of fluid through the lungs and whether the organs are becoming less stiff.
They also pump them with anti-inflammatory drugs and antibiotics.
The lungs continue to improve and at the four-hour mark, Keshavjee makes the call. The surgery can go ahead.
Another benefit of the XVIVO system is that it allows doctors to know how lungs will function before they are transplanted, thereby reducing the risk of death.
“I already know that the lungs are going to work before I even start the operation. That is transformative. Before, you would find out after,” Keshavjee says.
He continues with his other duties around the hospital, while another operating room is made ready for the transplant surgery and the patient is told the good news.
Seven hours after the lungs arrived at the hospital, the transplant begins.
The room is filled with music from Keshavjee’s iPod: Hedley, Florence and the Machine, Lady Gaga. His 15-year-old daughter’s selection.
In Keshavjee’s tool kit are more than 100 sterilized surgical instruments, including different sizes of clamps, forceps, scissors and what look like wrenches. There are even power tools.
Keshavjee opens the patient’s chest horizontally using an electric sternum saw so that it lifts like the hood of a car.
He removes and replaces the lungs one at a time. When the first one comes out, the signs of disease are apparent. It is bright red with inflammation and black lines run through it.
It takes the surgeon only 45 minutes to sew in each new lung. He expertly sutures them to the patient’s bronchus, pulmonary artery and veins, attaching them to the heart.
Each lung is slowly re-perfused with the patient’s own blood. Within minutes, the thousands of tiny blood vessels in the organs fill.
The right lung is done first. It inflates as it fills for the first time with the transplant patient’s own breath of air.
“When you stop to think about what we are doing, it is pretty amazing,” Keshavjee exclaims.
Before the patient is sewn up, samples of his new lungs are taken for research.
Keshavjee has big plans to take the technology even further by modifying transplanted lungs with gene therapy and stem cell therapy so they that patients don’t need to take anti-rejection drugs. Ultimately, he hopes to be able to build new lungs.
“Can you strip all the cells out of it, keep the skeleton, the scaffold and then take your bone marrow, your stems cells and build a lung that is you?”
Twelve hours after the surgery, the patient is removed from the ventilator. Where he had difficulty breathing with oxygen support before, he is now easily breathing on his own.
The day after the surgery, he is out of his bed and able to eat a meal of clear fluids.
One of the first things that strikes the patient is that he can get through a meal without have to stop for a break to catch his breath.
“It’s just a simple thing, but he can’t recall when he was last able to do that,” Keshavjee says.
Without the transplant and the ability to salvage lungs that were otherwise unusable, there was a more than 50 per cent chance the man would have died within the year.
The Toronto XVIVO Perfusion System has saved this man and has the potential to save many more lives as other countries adopt it. There are plans to use it for other organs, aside from lungs, as well.
“I think the impact of this will be changing the 15 per cent world utilization (for donated lungs) to 50 per cent. That is more than tripling the number of lung transplants done around the world,” Keshavjee says.
“This came from here and it’s going to impact the world.”
In Ontario, you can register your consent to be an organ and tissue donor online at beadonor.ca.

“You Have the Power to Donate Life – Sign-up today! Tell Your Loved Ones of Your Decision”

Thursday, December 15, 2011

First ‘ex-vivo’ Lung Transplants Performed in New York

In Canada, Dr. Shaf Keshavjee and his team implemented investigational trials of the Toronto ex-VIVO Lung Perfusion System which has been highly successful in saving the lives of many patients who would normally not have received their donor lungs because they were unsuitable for transplant. Only about 15% of donor lungs world-wide are acceptable for transplantation since lungs are susceptible to injuries during the brain-death process or from intensive care related lung complications. Moreover, organ retrieval often occurs before the lungs can recover from their injuries. View a video presentation of the EX-vivo system by Dr. Keshavjee at TEDMED 2010

medindia.net

Recipients of first transplanted lungs assessed and reconditioned in the operating room, a technique with the potential to dramatically boost the availability of lungs for transplant were two elderly New Yorkers. The experimental procedure was performed by Dr. Frank D'Ovidio at NewYork-Presbyterian Hospital/Columbia University Medical Center.


The "ex vivo" or outside-the-body approach involved removing lungs from a deceased donor, then enclosing them inside a transparent dome and connecting them to a cardiopulmonary pump and a ventilator. For four hours, the lungs were infused with nutrients and antibiotics. They were gradually warmed to body temperature, ventilated and oxygenated -- a process that resembles breathing, with the lungs inflating and deflating. Once determined to be viable, the lungs were immediately transplanted into the patients.

"Assessing lungs this way gives us a much more precise picture of how they should perform after transplant, and the reconditioning process may actually improve the chances of success," says Dr. D'Ovidio, associate surgical director of the lung transplant program at NewYork-Presbyterian Hospital/Columbia University Medical Center and assistant professor of surgery at Columbia University College of Physicians and Surgeons.

Traditionally, transplant surgeons have relied on a less sophisticated assessment. "Now with the ex vivo method, not only can we see the lungs inflate and deflate, but we also get hard data on how they function by monitoring multiple parameters and ultimately making sure that the gas exchange is happening at the level it needs to," continues Dr. D'Ovidio.

Going forward, the ex vivo procedure could significantly increase the availability of donor lungs, says Dr. D'Ovidio. "This has the potential to do for lung transplant what perfusion has done for kidney transplant. With the tool to better assess, recondition and possibly repair the organs, we can increase the number available to patients who desperately need them."

Currently, fewer than 30 percent of donor lungs are acceptable for transplantation, but physicians say ex vivo has the potential to double this figure as the reconditioning process is refined and improved.

The recent transplants at NewYork-Presbyterian/Columbia are part of an ongoing FDA investigational multicenter clinical research trial designed to compare outcomes from lung transplants using the ex vivo technique with those using the traditional method. This investigational trial, currently taking place in the United States, is coordinated and funded by Vitrolife, makers of the ex vivo perfusion system.

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Tell Your Loved Ones of Your Decision”
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Your generosity can save or enhance the lives of up to fifty people with heart, kidneys, liver, lungs, pancreas and small intestine transplants (see allotransplantation). One tissue donor can help by donating skin, corneas, bone, tendon, ligaments and heart valves
Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant. Organs can save lives, corneas renew vision, and tissue may help to restore someone's ability to walk, run or move freely without pain. Life Begins with You.

Saturday, October 30, 2010

Dr. Shaf Keshavjee presents EXVIVO Lung Perfusion system at TEDMED

TEDMED is one of the most prestigious annual events where leaders in the medical field discuss their ideas and I'm pleased to see that Dr. Shaf Keshavjee was an invited speaker. The first speaker of the event, he followed double-lung transplant recipient soprano Charity Tillemann-Dick's opening song “I Could Have Danced All Night” Dr. Keshavjee is my lung transplant surgeon and it's been my privilege to see the development of the Toronto EXVIVO Lung Perfusion System from it's early beginnings. Click here for a video of the system.

TEDMED celebrates conversations that demonstrate the intersection and connections between all things medical and healthcare related: from personal health to public health, devices to design and Hollywood to the hospital. TMED was held Oct 26-29 in San Diego.



By Katherine Hobson The Wall Street Journal Blogs

Last night at view video, Shaf Keshavjee, director of the Toronto Lung Transplant Program, asked for volunteers to come onstage and touch a breathing pig lung, which was hooked up to a machine that kept it essentially “alive.”

Martha Stewart, seated up front, raised her hand, so minutes later she — and a handful of other conference participants — had donned rubber gloves and were grasping the lung as the machine helped it “breathe.” (We halfway expected her to offer up a really good offal recipe to the crowd.)

The tool Keshavjee had brought with him was essentially a mini heart-lung machine but in reverse. It permits the lung to stay at room temperature and function as usual — removing carbon dioxide from blood (a cellular solution, in this demonstration) and adding oxygen. When a human lung retrieved from a deceased donor is hooked up to the machine, physicians get the luxury of time to assess its condition and then treat it using targeted methods, including gene and cellular therapy, before transplanting it into the recipient. At that point, it’s become a “super organ,” as Keshavjee says.

Using conventional methods, transplanted lungs are cooled to slow deterioration and then transplanted, with little time to assess their condition or repair damage. Keshavjee says this new method has allowed some 30 patients to receive donated and repaired lungs that wouldn’t have ordinarily been used.

He says the holy grail for the pre-op repair process would be to treat donated lungs while they’re outside the body to avoid rejection by the host, to “make it like self.”

More from TEDMED:
pagingdrgupta.blogs.cnn.com

Katherine Hobson on double-lung transplant recipient soprano Charity Tillemann-Dick's opening song “I Could Have Danced All Night”


“You Have the Power to Save Lives – Register to be an organ and tissue donor & Tell Your Loved Ones of Your Decision”
Register to be a donor in Ontario at Trillium Gift of Life Network NEW for Ontario: recycleMe.org - Learn The Ins & Outs Of Organ And Tissue Donation. Register Today! For other Canadian provinces click here
In the United States, be sure to find out how to register in your state at ShareYourLife.org or Download Donor Cards from OrganDonor.Gov
In Great Britain, register at NHS Organ Donor Register
In Australia, register at Australian Organ Donor Register
Your generosity can save or enhance the lives of up to fifty people with heart, kidneys, liver, lungs, pancreas and small intestine transplants (see allotransplantation). One tissue donor can help by donating skin, corneas, bone, tendon, ligaments and heart valves

Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant. Organs can save lives, corneas renew vision, and tissue may help to restore someone's ability to walk, run or move freely without pain. Life Begins with You

Thursday, April 29, 2010

Ex Vivo Lung Perfusion Renders Previously Unacceptable Lungs Usable

I've had the pleasure of visiting the labs in Toronto where this groundbreaking research is taking place and the results as described here offer great promise in having a global impact, with the potential to double the number of lungs available for transplant. Here is a video describing the EX Vivo Lung system:



By Caroline Helwick Medscape Pulmonary Medicine

April 28, 2010 (Chicago, Illinois) — Assessment and reconditioning of extended or initially rejected donor lungs using ex vivo lung perfusion (EVLP) is safe and leads to favorable outcomes after transplantation, according to results from the HELP trial — the largest clinical experience of EVLP to date — conducted at the University of Toronto in Ontario.

The trial results were presented here at the International Society for Heart & Lung Transplantation 30th Anniversary Meeting. The study employed the normothermic acellular Toronto XVIVO system (Vitrolife). "In the HELP trial, we aimed to determine the safety of transplanting initially rejected donor lungs after ex vivo re-assessment and reconditioning," said principal investigator Marcelo Cypel, MD, from the Toronto Lung Transplant Program of the University of Toronto, who presented the results.

The early outcomes of transplant after EVLP are at least equivalent to those using conventionally assessed and preserved donor lungs, said Dr. Cypel.

"Worldwide, only about 15% of donor lungs are accepted for transplantation. EVLP is a new technique that allows time to accurately assess the lung and to optimize function of injured donor lungs that would otherwise not be used," Dr. Cypel explained.

HELP was a prospective nonrandomized trial that included donor lungs that were considered unacceptable on the basis of current clinical criteria and that met study inclusion criteria. Donors were required to have a partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio of 300 mm Hg or less, or of more than 300 mm Hg with additional donor risk factors (multiple blood transfusions, pulmonary edema, donor cardiac death). Poor oxygenation or poor lung compliance was the primary reason for unsuitability.

The lungs were subjected to EVLP at 37 °C with Steen solution for 4 hours. The assessment of transplantability was made after examining lung function in the system. Organs with a partial pressure of oxygen (pO2)/FiO2 ratio of more than 400 mm Hg during EVLP were transplanted. The primary end point was a primary graft dysfunction (PGD) score of 2 to 3 within 72 hours of transplantation. Secondary end points were 30-day mortality, length of stay in the intensive care unit (ICU), length of stay in the hospital, length of intubation, proportional survival, and biomarkers in perfusate and lung tissue.

Between September 2008 and January 2009, there were 309 donors, and 129 lungs (41%) were used for 136 transplants. Of these, 25 were enrolled in the HELP trial and 22 went to transplant. These patients were compared with 114 conventionally treated control subjects. Of the 22 patients in the EVLP group, 19 had extended criteria — "no EVLP available and transplanted with concerns" — or were outright rejected.

Of the 25 lungs treated with EVLP, 22 improved sufficiently to be transplanted, and all functioned well after transplantation, the investigators reported.

Donor characteristics were similar between the HELP and control groups, except the HELP group had significantly more donors from cardiac deaths, and more patients with abnormal bronchoscopy, lower PaO2, and positive cultures. The donor score was also significantly higher in the HELP group (6 vs 4; P < .0001). Recipient demographics were similar between the groups.

The total preservation time (time to implantation) was 10 hours (range, 6 to 17 hours) for the EVLP group, after which a significant improvement in lung function was observed in the treated organs, Dr. Cypel reported.

In the majority of cases, PGD grade after EVLP was 0 to 1. "A few with good lung function after EVLP had PGD grade 3 upon ICU arrival, but this quickly improved to 0 or 1 within 24 hours," he said. PGD grade 2 was more common in the control group. More than 30% of these patients had PGD grade 2 at 24 hours, compared with 10% of the HELP group. By 72 hours, PGD grade 2 was observed in approximately 25% of the control group and 15% of the HELP group.

 "For recipient outcomes, we saw no significant differences between the HELP population and controls," Dr. Cypel reported. This included 30-day mortality, time to extubation, ICU and hospital length of stay, PaO2/FiO2 ratio upon ICU arrival, and need for extracorporeal mechanical oxygenation.

 Thirty-day mortality was 10.5% in the HELP group and 5.2% for other transplantations. No patients required extracorporeal mechanical oxygenation after EVLP, compared with 3.5% with conventional transplant. At 560 days posttransplant, survival was 80% for each group, he reported.

 "Our system was able to discriminate between the lungs that were acceptable, and therefore transplanted (n = 22), and those that were rejected (n = 3), Dr. Cypel noted. In general, the rejected lungs had lower gas exchange, higher pulmonary vascular resistance, and higher airway pressure. Interestingly, the rejected lungs also had higher levels of inflammatory cytokines, he said.

 "Using the inflammatory chip (Xceed), we are exploring the inflammatory gene profile before and after EVLP, trying to identify what these changes mean," he said. Dr. Cypel added that identification of biological predictors of donor lung quality during EVLP, perhaps through a genetic profile, would be helpful in the evolution of this technology.

Future May Be "Personalized" Organ Transplant

Dr. Cypel's presentation was followed by an invited lecture by Shaf Keshavjee, MD, the F.G. Pearson–R.J. Ginsberg Chair in Thoracic Surgery and director of the Toronto Lung Transplant Program. Dr. Keshavjee was involved in the HELP study, but he expanded upon the study's findings to provide a broader picture of EVLP.

He said that the concept of donor organ management is changing toward a paradigm that focuses on "regeneration, not death" of the organ. "The focus has been on slowing down death, rather than facilitating recovery and regeneration," Dr. Keshavjee said. "Currently, we only find out how the organ works after we implant it."

Currently, assessment of organ function is impossible at procurement, leading to the rejection of questionable organs that might be accepted in the setting of ex vivo evaluation. Going beyond assessment, ex vivo optimization of organs would increase the percentage of transplantable organs, with very few organs rejected in the end, Dr. Keshavjee explained.

"How do we get there? We need to develop a stable, reliable ex vivo maintenance perfusion technique and treatment platform," he said, "and develop a 'treatment arsenal' that is capable of injury-specific repair and immunological preparation for tolerance."

A number of questions remain with regard to organ-specific needs (heart, lung, liver) and approaches, mechanical and engineering factors, perfusate composition, and so forth. "Different resuscitation objectives will require different perfusion strategies," Dr. Keshavjee pointed out.

There are short-term issues, he added, such as thrombolysis and metabolic support, intermediate needs that might be addressed by gene therapy and immunomodulation, and long-term needs that call for regenerative medicine approaches. Functional repair of human donor lungs by interleukin-10 gene therapy has already been reported by the Toronto group, he noted (Sci Transl Med. 2009;1:4ra9).

The HELP study was funded by Vitrolife. Dr. Cypel has disclosed no relevant financial relationships. Dr. Keshavjee reports receiving grants and research support from Vitrolife and Astellas Canada, and holding the Chair in Transplantation Research, which is funded by Wyeth (Pfizer).

International Society for Heart & Lung Transplantation (ISHLT) 30th Anniversary Meeting: Abstract 258. April 23, 2010.

“You Have the Power to Save Lives – Register to be an organ and tissue donor & Tell Your Loved Ones of Your Decision”
Register to be a donor in Ontario or Download Donor Cards from Trillium Gift of Life Network. NEW for Ontario: recycleMe.org - Learn The Ins & Outs Of Organ And Tissue Donation. Register Today! For other Canadian provinces click here
In the United States, be sure to find out how to register in your state at ShareYourLife.org or Download Donor Cards from OrganDonor.Gov
In Great Britain, register at NHS Organ Donor Register
In Australia, register at Australian Organ Donor Register
Your generosity can save up to eight lives with heart, kidneys, liver, lungs, pancreas and small intestine transplants (see allotransplantation). One tissue donor can help 75 to 100 other people by donating skin, corneas, bone, tendon, ligaments and heart valves
Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant. Organs can save lives, corneas renew vision, and tissue may help to restore someone's ability to walk, run or move freely without pain. Life Begins with You

Monday, December 21, 2009

Reconditioned lungs used in UK transplant

It's gratifying to see that more centers, such as the Freeman Hospital in the UK, are using the Ex-vivo (outside the body) Lung Perfusion System that allows surgeons the opportunity to assess and treat injured donor lungs, while they are outside the body, to make them suitable for transplantation. Read my earlier post on the World-first Toronto XVIVO Lung Perfusion System.

Research breakthrough gives new life to lungs for transplantation

BBC News

Donor lungs normally rejected as too damaged can now be 'reconditioned' for transplant, say doctors.

Cystic fibrosis patient James Finlayson is the first in the UK to receive lungs revived using oxygen, nutrients and antibiotics.

Newcastle-based scientists and surgeons suggest it could eventually double the number of available organs.

Current shortages mean that many patients die waiting for their operation.

The fragile nature of the lung means that it is far more vulnerable to damage during the final hours of life.

At present, four out of five potential donor lungs turn out to be unsuitable, but the recent operation at the Freeman Hospital in Newcastle was the first in the UK to use one of these 'rejected' organs.

The technique involves connecting the lungs to a heart bypass machine then pumping a tightly-controlled solution of oxygen, proteins, antibiotics and nutrients over the damaged tissues.

This helps reduce inflammation, and even allows some damage to be repaired.

Regular checks are made on the ability of the lung to do its job of exchanging oxygen and maintaining airway pressure.

After approximately six hours, the lung has been improved sufficiently to be transplanted into the patient.

'Poor condition'

Mr Finlayson was discharged from hospital at the end of November, and is said to be recovering well.

Professor Andrew Fisher, from the Institute of Cellular Medicine at Newcastle University, said that the lung chosen for the pioneering operation had been in such poor condition that it would have been "rejected outright" by any transplant centre in the world.

He said: "We now have the potential to double the number of lungs available for transplant - it will offer new hope to a great number of patients."
Canadian surgeons have been using the technique for approximately a year longer, and Professor Fisher said that early signs showed similar survival rates for patients given "reconditioned" lungs.

He said that other UK transplant centres were now involved in work to use the technique more widely, but that greater investment would be needed in transplant services if the number of operations were to rise significantly.

The research was funded by the Cystic Fibrosis Trust, and a spokesman said that hundreds of people with the disease, and other lung conditions, could benefit.

She said: "At present, around half of those with Cystic Fibrosis on the transplant list die waiting for donor lungs."

Dr Keith Prowse of the British Lung Foundation said: "This is a very exciting procedure and if it leads to more lungs being available for transplant operations, it will be a hugely welcome development.

"There is an increasing demand for lung transplants but just not enough lungs available."

“You Have the Power to Save Lives – Register to be an organ and tissue donor & Tell Your Loved Ones of Your Decision”

Register to be a donor in Ontario or Download Donor Cards from Trillium Gift of Life Network. NEW for Ontario: recycleMe.org - Learn The Ins & Outs Of Organ And Tissue Donation. Register Today! For other Canadian provinces click here

In the United States, be sure to find out how to register in your state at ShareYourLife.org or Download Donor Cards from OrganDonor.Gov

In Great Britain, register at NHS Organ Donor Register

In Australia, register at Australian Organ Donor Register

Your generosity can save up to eight lives with heart, kidneys, liver, lungs, pancreas and small intestine transplants. One tissue donor can help up to 100 other people by donating skin, corneas, bone, tendon, ligaments and heart valves

Has your life been saved by an organ transplant? "Pay it forward" and help spread the word about the need for organ donation - In the U.S. another person is added to the national transplant waiting list every 11 minutes and 18 people die each day waiting for an organ or tissue transplant.

Wednesday, December 16, 2009

Scientists record first injured human donor lungs repair with gene therapy

This ground-breaking research in lung transplantation will have a global impact and I am very fortunate to have had the opportunity to see the initial lung perfusion technique being perfected using pig lungs. The senior scientist leading this research, Dr. Shaf Keshavjee, is the surgeon that performed my lung transplant more than 7 years ago and I am very pleased to report on this outstanding success.

Gene therapy used for transplant lung repair
Scientists hope to reduce inflammation in lungs donated for transplantation by maintaining them in a special perfusion chamber and using gene therapy to administer interleukin-10. (Photo credit: Nathan Sulyma, RN/Toronto General Hospital)

FOR the first time in the world, transplant surgeons at Toronto General Hospital, University Health Network, Canada, used a new technique to repair an injured donor lung that was unsuitable for transplant, and then successfully transplanted it into a patient. They said the use of this technique could significantly expand the lung donor organ pool and improve outcome after transplantation. CHUKWUMA MUANYA writes with agency reports.
Chukwuma Muanya The Guardian

FOR the first time, scientists in the McEwen Centre for Regenerative Medicine, University Health Network, Canada, have successfully used gene therapy to repair injured human donor lungs, making them potentially suitable for transplantation into patients. This technique could significantly expand the number of donor lungs by using organs that are currently discarded, and improve outcomes after transplantation.

Dr. Shaf Keshavjee
In their pioneering work, a team of researchers led by Dr. Shaf Keshavjee, above, Senior Scientist at the McEwen Centre for Regenerative Medicine, University Health Network and Director of the Lung Transplant Program, University Health Network developed a technique of ex vivo gene delivery to donor lungs, before they are implanted into a recipient's body.

The technique was shown to be simple and effective in improving lung function. Their results, "Functional Repair of Human Donor Lungs by IL-10 Gene Therapy," are published in the October 28, 2009 edition of the journal Science Translational Medicine.

"This work is a big step in using regenerative strategies to repair injured lungs," says Keshavjee, who is also Director, Latner Thoracic Research Laboratories and Professor and Chair, Division of Thoracic Surgery at the University of Toronto. "For the first time, we hope to improve the health of donor lungs that we could not have used before by using gene therapy to decrease inflammation and repair cells before transplantation."

Keshavjee also emphasizes that clinical trials on humans would be the next step in testing this promising approach before it could be used on patients waiting for lung transplants. In these future clinical trials, lungs repaired with the gene therapy will be offered to patients waiting for a life-saving lung transplant.

The process of gene therapy used on injured lungs will be carefully explained to the patients and, if they consent, the patients will be potentially transplanted with the repaired lungs should no other suitable donor lungs become available.

"This work opens the door for a variety of therapies that could potentially be applied to repair various injuries in other donor organs to improve the safety and outcome of transplants," adds Keshavjee.

Using a novel approach to overcome some of the challenges of gene therapy, the researchers first developed a strategy to preserve lungs at normal body temperature, with the lungs kept outside the body in a protective dome.

The Toronto XVIVO Lung Perfusion System continuously pumps a bloodless solution of oxygen, proteins and nutrients into injured donor lungs, mimicking normal physiological conditions. This makes it possible for the injured cells to begin repairing themselves, and also sets the stage for more sophisticated repair techniques to be applied to donor lungs.

Working with pig and then human donor lungs, which were unsuitable for transplantation, the researchers first placed the lungs on the Toronto XVIVO Lung Perfusion System to warm them to normal body temperature. Then, using a specially engineered adenovirus vector -- a common cold virus -- the researchers used a bronchoscope to inject the vector with an added IL-10 gene through the windpipe into the human lungs.

The study found that lungs maintained on the Toronto Lung Perfusion System alone, the control group, did not deteriorate and remained stable. However, the donor lungs that received the gene therapy, in addition to the ex vivo perfusion, significantly improved their function with regards to blood flow throughout the lungs and their ability to take in fresh oxygen and get rid of carbon dioxide. The boosted IL-10 effect lasts for up to 30 days in the lung.

The authors state that transplanting lungs which function better from the start would lead to more predictable, safer outcomes, shorter periods of mechanical ventilation and shorter intensive care unit stays for patients.

"It's as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory," explains Keshavjee, "This protein down-regulates or decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient's immune system which rejects the transplanted organ."

The IL-10 gene is found normally in animal and human cells, and plays a role in inhibiting the immune response to infection or foreign materials such as transplanted organs. The researchers found that the lungs begin producing the new IL-10 anti-inflammatory proteins about six hours after insertion.

More than 80 per cent of potential donor lungs are injured and show inflammation during the process of brain death and intensive care related complications, and cannot be used for transplantation. Moreover, inflammation and organ rejection are the two main complications after transplant surgery.

"Everything we can do to prevent lung injury, especially in the first 72 critical hours after surgery, would have a significant impact on survival and quality of life after transplantation," notes Dr. Marcelo Cypel, a transplant surgical fellow at Toronto General Hospital who is the first author of the paper. Cypel adds that patients who have severe early lung injury are at greater risk of dying after surgery, and have higher rates of organ rejection later on.

Currently, more than 50 patients are waiting for either a lung or heart-lung transplant in Ontario, Canada. About 20 per cent of those on the wait list will die before they receive a lung transplant. In Canada, the number of people waiting for a lung transplant has doubled in the past 10 years, with 252 Canadians waiting to receive a lung transplant in 2006, compared to 119 in 1997. Two hundred and ninety-nine (299) Canadians died while waiting for a lung transplant between 1997 and 2006.

It is estimated that the number of donor organs available for lung transplants could easily be doubled with this technique to treat and improve donor lungs.

Other members of the team who contributed to this study include: Mingyao Liu, Matt Rubacha, Jonathan Young, Shin Hirayama, Masaki Anraku, Masaaki Sato, Marc de Perrot, Thomas Waddell of the McEwen Centre for Regenerative Medicine and the University of Toronto; Jeffrey Medin, Ontario Cancer Institute, Princess Margaret Hospital; and Arthur Slutsky, St. Michael's Hospital.

The study was supported by grants from the Canadian Institutes of Health Research and the Center for Gene Therapy, National Institutes of Health, U.S.

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