Japan: Pfizer To Launch Champix(R) The First Prescription Oral Smoking Cessation Aid In The Country

Pfizer Inc announced that on May 8, 2008, it will launch Champix® Tablet 0.5mg/1mg (varenicline tartrate), a novel smoking cessation aid for smokers with nicotine dependence in Japan, which has one of the highest rates of smoking among developed nations.

Champix was developed as the first non-nicotine drug designed for smoking cessation in the United States and will be the first oral smoking cessation aid available in Japan.

“Pfizer is delighted to be able to provide patients and physicians in Japan with Champix, a breakthrough medicine for smoking cessation that has helped millions of smokers who want to quit,” said Jeff Kindler, chairman and chief executive officer of Pfizer. “Furthermore, we are gratified that health authorities in Japan recognize the benefits of therapies such as Champix that address a major unmet medical need.”

Champix’s approval in Japan was based on a 12-week, randomized, double-blind, placebo-controlled study in Japanese smokers who wanted to quit smoking. The primary endpoint, the percentage of subjects who did not smoke at all during the four consecutive weeks between Week 9 and Week 12 was 65.4 percent (85/130 cases) in the Champix 1mg twice-daily group and 39.5 percent (51/129 cases) in the placebo group, a statistically significant difference between the two groups. The most common side effects of Champix were nausea, headache, and constipation, but most of them were mild.

“Smoking is a chronic, relapsing medical condition and one of the leading causes of preventable disease, death and disability in the world,” said Hiromitsu Iwasaki, president and chief executive officer of Pfizer Japan. “Champix represents a major clinical advance for smoking cessation which we hope, together with counseling, will help patients end their addiction to the nicotine in tobacco.”

With the launch of Champix, Pfizer Japan will introduce a website for patients with nicotine dependence called “SUGU KIN-EN (Smoking Cessation Now) at www.sugu-kinen.jp” as of May 8, 2008. This website provides easy-to-understand guidance on smoking cessation and treatment options. The website also offers a list of medical institutions that provide smoking cessation treatment throughout Japan.

Pfizer Japan

Night Home Hemodialysis Shown To Be As Good As Transplant In Treating Kidney Failure

For the first time, it has been shown that patients who receive night home hemodialysis live just as long as those who receive kidney transplants from deceased donors.

In a study entitled, “Survival among nocturnal home hemodialysis patients compared to kidney transplant recipients,” published in the international September issue of Nephrology Dialysis Transplantation, a total of 1,239 patients were followed for up to 12 years. Night home hemodialysis patients were compared to patients who received either a deceased donor kidney transplant or a living donor kidney transplant. The study found that the survival between night home dialysis patients and those who received kidney transplants from deceased donors was comparable, while the survival of the patients who received a transplant from a living kidney donor was better than both the other groups.

These results suggest that night home hemodialysis, an intensive dialysis of six to eight hour sessions for up to seven times a week, may be a “bridge to transplant” or a “suitable alternative” to transplant should a patient be too high risk for a transplant or not be able to get a living or deceased donor as the organ shortage continues. Night home hemodialysis patients were from the Toronto General and Humber River Regional Hospitals, both hospitals together representing the largest and longest established group of such patients world-wide.

“This study allows me to actually answer what my patients have been asking me for over a decade: ‘What does night home hemodialysis mean for my life span?’ I can now tell them that this specific dialysis option is as good as getting a transplant from a deceased donor,” says Dr. Christopher Chan, Medical Director of Home Hemodialysis at Toronto General Hospital, University Health Network, the R. Fraser Elliott Chair in Home Dialysis and Associate Professor, University of Toronto.

Until this study, there has been no long-term data on night home hemodialysis patient survival, or on how this type of treatment compares to transplantation. In the study, night home hemodialysis patients’ data was carefully matched with deceased and living donor kidney transplantation mortality data from the U.S. Renal Data System on characteristics such as age, race, diabetic status and duration of treatment with conventional in-centre dialysis prior to treatment.

The proportion of deaths in each group was then measured, with final figures of 14.7% for night home hemodialysis patients; 14.3% for patients with transplants from deceased donors; and 8.5% for patients with transplants from living donors.

These results diverge from the evidence to date that dialysis is inferior to transplantation, pointed out Dr. Chan, adding that there is much benefit to be gained by long, frequent dialysis.

Florence Tewogbade, 27, has been on home hemodialysis since April 2008, after trying conventional dialysis. “It has changed my life,” she said. “I can now work, go to school, look forward to a future and be self-reliant.” Florence was on the transplant waiting list in 2004, but her living donor was found to be ineligible.

Florence says that she would have had to wait about 10 years for a kidney from a deceased donor because of her specific risk factors for receiving a transplant. “I always thought that transplant was the only option, so I didn’t consider home hemodialysis,” she said. “I thought I couldn’t do it. But here I am, doing it, and living a normal life.”

Other researchers involved in the study include Robert Pauly, University of Alberta Hospital, John Gill and Caren Rose, St. Paul’s Hospital, UBC, Reem Asad, TGH, Anne Cherry, UHN, Andreas Pierratos, Humber River Regional Hospital.

This study did not require any external funding.

Kidney Facts:

– Shortage of organs and tissues remains a concern for Canada, and our national donation rates lag far behind many countries; in fact, we have one of the lowest donation rates among developed
countries at 14 donors per million people, while Spain, for e.g., has a rate of 35 donors per million

– Of the 4,195 Canadians on the waiting list for a transplant as of December 31, 2007, 2,963 (71%) were waiting for a kidney

– At any point in time, there are more than 1,000 patients waiting for a kidney transplant in Ontario (more than any other organ)

– In the GTA, adults usually wait 4 – 10 years, depending on the blood group, for a kidney to become available, and about 2% of people on the waiting list die waiting for a kidney each year

– The number of patients being treated for end-stage kidney failure in Ontario climbed by nearly 20% in five years from 15.4 people per 100,000 in 1995 to 19.3 per 100,000 in 2000

– Each day, an average of three Ontarians learn that their kidneys have failed and their survival depends on dialysis treatments or a kidney transplant

– Currently, there are more than 10,000 Ontarians being treated for chronic kidney disease
– The number of new patients increases by 10-15%

– Reasons for this growth include an aging population and an increasing number of people with diabetes and diabetes complications

About Toronto General Hospital, University Health Network

Toronto General Hospital is a partner in the University Health Network, along with the Toronto Western Hospital and the Princess Margaret Hospital. These research hospitals are affiliated with the University of Toronto. The scope of research at Toronto General Hospital has made this institution a national and international resource for education and patient care, and a leader in diabetes, transplantation, cardiology, surgical innovation, infectious diseases and genomic medicine. The night home hemodialysis program at Toronto General Hospital began in 1999. It now has ninety-five (95) patients, making it one of the largest such programs in the world.

Source: University Health Network (UHN)

Postponing Surgery Reduces Long Term Side Effects For Children With Kidney Cancer

Children given chemotherapy before surgery to treat the most common form of childhood kidney cancer, called Wilms’ tumour, require less treatment and experience fewer long term side effects than if they have immediate surgery, according to trial results revealed at today’s NCRI Cancer Conference and published in the European Journal of Cancer*.

The Children’s Cancer and Leukaemia Group (CCLG)**, funded by Cancer Research UK, undertook a ten-year trial involving 205 patients with newly diagnosed Wilms’ tumours. The patients were randomly assigned to receive either immediate surgery or six weeks pre-operative chemotherapy and then surgery. Depending on the size of their tumours and how much they had grown, all children on the trial were given chemotherapy, radiotherapy or both after their surgery to kill off any remaining cancer cells.

Overall survival between the two groups was the same, but the researchers found that giving six weeks pre-operative chemotherapy enabled easier removal of tumours. Also, 20 per cent fewer children needed radiotherapy or the powerful chemotherapy drug doxorubicin after their surgery, minimising their risk of long-term side effects. The results of this trial are strong enough to conclude that pre-operative chemotherapy should be become standard for the treatment of Wilms’ tumours throughout the UK.

Around 78 children in the UK are diagnosed with Wilms’ tumour each year and it is the most common type of kidney cancer that children can get. Wilms’ tumours are most likely to occur in children under five – they can appear in older children and adults but this is rare. Wilms’ tumour is one of the most curable childhood cancers with nine out of ten children being cured in the long term.

The purpose of this trial was to see if doctors could avoid giving children radiotherapy and the powerful chemotherapy doxorubicin if they did not need it. Giving radiotherapy to the kidneys of young children can be damaging because the kidneys are situated close to the spine and the effects of the radiotherapy can stunt growth and sometimes lead to spinal deformities. Doxorubicin is used to treat children with more advanced tumours, but it may cause heart problems later in life.

Study author Dr Christopher Mitchell, from the Oxford Radcliffe Hospital, said: “Deciding what is the best way to treat Wilms’ tumours has been under debate for many years and this study was the first time that the two treatment methods were compared in a randomised clinical trial. We were able to identify a group of patients who could benefit from a reduction in treatment without compromising their survival chances. For some children with advanced tumours, delaying their surgery reduced the size of their tumours enough to prevent them needing intensive treatment after surgery. This improvement in quality of life for patients is significant and we hope children diagnosed with Wilms’ tumours in the future will benefit from our findings.”

Kate Law, Cancer Research UK’s director of clinical trials, said: “These are significant results that have led to a change in the way children in the UK are treated for this disease. As more children survive this type of cancer, anything that adds to our understanding of how to reduce the long-term side effects of the treatment is important work.”

*Immediate nephrectomy versus pre-operative chemotherapy in the management of non-metastatic Wilms’ Tumour; Results of a Randomised Trial (UKW3) by the UK Children’s Cancer Study Group. Christopher Mitchell et al. (2006). European Journal of Cancer.

This study was supported by a grant to the UK Children’s Cancer Study Group from Cancer Research UK. Wilms’ tumours

Wilms’ tumours, also known as nephroblastomas, are a type of kidney cancer that affects children. Kidney cancer in children is rare but this is the most common type they can get. More than 9 out of 10 kidney cancers (95 per cent) found in children are Wilms’ tumours. Wilms’ tumours usually only affect one kidney (unilateral) but in about 7 out of every 100 children (7 per cent) it can affect both (bilateral).

**The Children’s Cancer and Leukaemia Group

Cancer Research UK is the major funding provider of the Children’s Cancer and Leukaemia Group (formally the UK Children’s Cancer Study Group) and funds the UK clinical trials work of the group via its coordinating centre in Leicester and 22 paediatric centres throughout the British Isles.

The Children’s Cancer and Leukaemia Group is the national professional body responsible for the organisation, treatment and management of virtually all children with cancer in the UK. The group is acknowledged as one of the world’s leading childhood cancer clinical trial groups and over the past five years there has been significant progress and success in its trials, resulting in improvements in survival.

Cancer Research UK is the largest supporter of research into children’s cancer in the UK. The charity is committed to improving survival and quality of life for every child with cancer.

Cancer Research UK

– Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer.

– Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.

– Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.

– Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.

– Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.

– For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7009 8820 or visit our website.

About the National Cancer Research Institute (NCRI)

The National Cancer Research Institute (NCRI) was established in April 2001. It is a partnership between government, the voluntary sector and the private sector, with the primary mission of maximising patient benefit that accrues from cancer research in the UK through coordination of effort and joint planning towards an integrated national strategy for cancer research. Click here to visit the NCRI website.

The NCRI consists of: The Association of British Pharmaceutical Industry (ABPI); The Association for International Cancer Research; The Biotechnology and Biological Sciences Research Council; Breakthrough Breast Cancer; Breast Cancer Campaign; Cancer Research UK; Department of Health; Economic and Social Research Council; Leukaemia Research Fund; Ludwig Institute for Cancer Research; Macmillan Cancer Support; Marie Curie Cancer Care; The Medical Research Council; Northern Ireland Health and Personal Social Services Research & Development Office; Roy Castle Lung Cancer Foundation; Scottish Executive Health Department; Tenovus; Wales Office of Research and Development for Health & Social Care; Wellcome Trust; and Yorkshire Cancer Research. AstraZeneca is the gold sponsor for the NCRI Cancer Conference 2006.

Cancer Research UK

Vaccine Could Be Lethal Weapon Against Malaria, Cholera

Mankind may finally have a weapon to fight two of the world’s deadliest diseases.

A University of Central Florida biomedical researcher has developed what promises to be the first low-cost dual vaccine against malaria and cholera.

There is no FDA approved vaccine to prevent malaria, a mosquito-borne illness that kills more than 1 million people annually. Only one vaccine exists to fight cholera, a diarrheal illness that is common in developing countries and can be fatal. The lone vaccine is too expensive to prevent outbreaks in developing countries after floods, and children lose immunity within three years of getting the current vaccine.

“I’m very encouraged because our technique works well and provides an affordable way to get vaccines to people who need them most and can least afford them,” said lead scientist Henry Daniell.

Daniell’s team genetically engineered tobacco and lettuce plants to produce the vaccine. Researchers gave mice freeze-dried plant cells (orally or by injection) containing the vaccine. They then challenged the mice with either the cholera toxin or malarial parasite. The malaria parasite studies were completed in fellow UCF professor Debopam Chakrabarti’s lab.

Untreated rodents contracted diseases quickly, but the mice who received the plant-grown vaccines showed long-lasting immunity for more than 300 days (equivalent to 50 human years).

Results from the National Institutes of Health-funded research are published in this month’s Plant Biotechnology, the top-ranked journal in the field.

Clinical trials are needed, and Daniell is hopeful that the results with mice will translate to humans. It could be yet another example of plants delivering life-saving medicines.

The dual vaccine follows a string of other “green” vaccines developed in Daniell’s lab. He’s created vaccines against anthrax and black plague that generated a congratulatory call from the top U.S. homeland security official and was featured on the Discovery Channel. He’s also successfully grown insulin in plants to find what could be a long-lasting cure for diabetes. Daniell’s team continues to research these vaccines and is looking for investors to help fund clinical trials.

Producing vaccines in plants is less expensive than traditional methods because it requires less labor and technology, Daniell said.

“We’re talking about producing mass quantities for pennies on the dollar,” he said. “And distribution to mass populations would be easy because it could be made into a simple pill, like a vitamin, which many people routinely take now. There is no need for expensive purification, cold storage, transportation or sterile delivery via injections.”

For Daniell, his research is more than his day job. His passion to find vaccines for the world’s top 10 diseases as defined by the World Health Organization comes from growing up in India. He watched many of his childhood friends contract malaria, cholera and other diseases.

Daniell, a father of two, joined UCF’s Burnett School of Biomedical Sciences in the College of Medicine in 1998. His research led to the formation of the university’s first biotechnology company. Daniell also became only the 14th American in the last 222 years to be elected the Italian National Academy of Sciences. In 2007 he was named a Fellow of the American Association for the Advancement of Sciences.

“I’m not done yet,” he said. “I still have more diseases to attack.”

Other researchers working on the dual vaccine project include Abdoreza Davoodi-Semiromi, Melissa Schreiber, Samson Nallapali, Dheeraj Verma, Nameirakpam D. Singh and Robert K. Banks.

Zenaida Gonzalez Kotala

University of Central Florida

The Top-Down Approach To Evaluation And Management Of UTIs In Children

ORLANDO, FL (UroToday) – John Duckett Memorial Lecture

State of the art lecture by Dr. A. Barry Belman addressed the evaluation of children with a urinary tract infection. He discussed what is known as the “top down approach”.

The take home message of the lecture was to distinguish which children with vesicoureteral reflux are at high risk for renal scarring and long term effects of the process. The evaluation seems to favor a DMSA scan to assess renal defects in a child with VUR.

If the renal scan shows signs of scarring, then these children appear to be at a higher risk of subsequent scars or other deleterious effect of pyelonephritis. These children might benefit from surgical intervention.

Presented by A. Barry Belman, MD, at the Annual Meeting of the American Urological Association (AUA) – May 17 – 22, 2008. Orange County Convention Center – Orlando, Florida, USA.

Reported by UroToday Medical Editor Pasquale Casale, MD

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:

Copyright © 2008 – UroToday

Improving Understanding Of The Pathogenesis Of H1N1 Virus Using Medical Imaging

Researchers at the National Institutes of Health (NIH) have found that imaging can now be used as a tool for identifying severe cases of H1N1 and may play a key role in understanding the pathogenesis of the virus, possibly leading to earlier diagnoses of severe cases in the future, according to a study published online in the American Journal of Roentgenology. The study will be published in the December issue.

Imaging revealed a severe case of H1N1 after a patient had tested negative using a nasal swab rapid antigen test. Radiography (standard X-ray) showed peripheral lung opacities, and computed tomography (CT) revealed peripheral ground-glass opacities. Both findings raised suspicion of H1N1 and reports revealed that the patient later died from a severe case of H1N1.

“The role of radiologic imaging in epidemic detection and response is evolving, with imaging being used as a tool for identifying severe cases,” said Daniel J. Mollura, M.D., lead author of the study. “At the Center for Infectious Disease Imaging (CIDI) at the NIH, the study of influenza is a priority with a focus on achieving early diagnosis and understanding its pathogenesis,” he said.

“Early CT may help clinicians recognize cases of severe influenza and monitor response to treatment. More cases will certainly need to be analyzed and compared in the future, but this is a promising early result,” said Dr. Mollura.

This study is now posted online at ajronline and will appear in the December issue of the American Journal of Roentgenology.

Heather Curry

American Roentgen Ray Society

Newest Interventional Radiology Treatment Used To Bust Blood Clots In Legs: Pivotal National Trial

ATTRACT – the first major national trial of a catheter-based treatment for deep vein thrombosis – will evaluate the use of clot-dissolving drugs in combination with clot removal devices to prevent post-thrombotic syndrome in patients with DVT (the formation of a blood clot in a leg vein). PTS, a common irreversible complication of DVT, causes permanent damage to the veins, resulting in debilitating chronic leg pain, swelling, fatigue and/or skin ulcers. About 25 percent of DVT patients develop PTS when treated with blood thinners alone. While early treatment with blood thinners is important to prevent a life-threatening pulmonary embolism, blood thinners alone do not dissolve the existing clot, which remains in the leg. Preliminary studies have shown that interventional clot-busting treatments can – unlike standard DVT therapy – remove clots and have strong potential to prevent PTS. The outcomes of this pivotal multicenter trial – to be funded at more than $10 million by the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI) – are likely to change the way DVT is treated in the United States.

“The ATTRACT trial could fundamentally shift the 50-year-old DVT treatment paradigm to one that includes interventional clot removal as an essential element of standard DVT care,” said interventional radiologist Suresh Vedantham, M.D., who will lead the trial. “By funding this study, the NHLBI has clearly recognized the strong potential of interventional radiology clot removal treatments for DVT to improve public health,” added the associate professor at the Washington University School of Medicine’s Mallinckrodt Institute of Radiology in St. Louis, Mo.

ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) is a multicenter, randomized trial “that will definitively determine if the newest clot-busting treatment (pharmacomechanical catheter-directed thrombolysis or PCDT) prevents post-thrombotic syndrome in patients with DVT,” said Vedantham. PCDT combines the use of a clot-dissolving drug with a catheter-mounted miniature clot removal device, allowing an interventional radiologist to break up the clot and remove it from the vein, restoring blood flow. “PTS is a serious complication of DVT that is under recognized and potentially preventable if we are able to dissolve the clots early, before permanent damage to the vein occurs,” he noted. “Established PTS is a lifelong, irreversible condition for which there are no consistently effective treatments. Its prevention is extremely important; however, physicians have historically neglected the prevention of PTS,” said Vedantham. “The groundbreaking combination of clot-busting drugs with innovative device technology – pioneered by interventional radiologists – now enables clot removal in a safer and more efficient manner, often in a single procedure session. These advances will greatly increase the use of interventional DVT treatments,” added Vedantham.

“This research is critical. The Society of Interventional Radiology Foundation initiated a DVT research consensus panel four years ago, bringing together clinicians and scientists from all disciplines and from all settings – academia, private practice, government and industry – and determining the need for the ATTRACT trial,” said Michael Darcy, M.D., chair of the board of directors for SIR Foundation, a scientific foundation dedicated to fostering research and education in interventional radiology. The SIR Foundation has been a critical partner in developing the ATTRACT trial, helping to coordinate the site selection process and partnering with the ATTRACT research team to conduct the trial, said Vedantham.

DVT is the formation of a blood clot, known as a thrombus, in a deep leg vein. This can be a very serious condition that often causes permanent damage to the leg, known as post-thrombotic syndrome. Early treatment with blood thinners is important to prevent a life-threatening pulmonary embolism, but blood thinners do not dissolve the existing clot, which remains in the leg. While many patients’ clots will slowly dissolve over time, often the vein wall and vein valves become irreversibly damaged in the process. “PTS develops as a direct result of having the blood clot stay in the vein. The blood clot continues to block the vein and permanently damages its one-way valves, resulting in the pooling of blood in the leg, chronic leg pain, swelling and fatigue and sometimes skin ulcers. It’s logical that immediate clot removal will prevent PTS,” said Vedantham.

The ATTRACT trial – the first NIH-funded multicenter, randomized trial of any interventional DVT therapy – will begin later this year. The trial will assess the presence and severity of PTS, quality of life, relief of pain and swelling, safety and costs. At least 28 U.S. clinical centers will enroll 692 patients and monitor their health for two years, said Vedantham, who is chair of the DVT Research Committee of SIR’s Venous Forum and vice chair of the Venous Disease Coalition. The Society of Interventional Radiology is a member of the Venous Disease Coalition.


About the Society of Interventional Radiology Foundation

SIR Foundation is a scientific foundation dedicated to fostering research and education in interventional radiology for the purposes of advancing scientific knowledge, increasing the number of skilled investigators in interventional radiology and developing innovative therapies that lead to improved patient care and quality of life.

Interventional radiologists are vascular experts who invented angioplasty and the catheter-delivered stent, which were first used in the legs to treat peripheral arterial disease. They provide vascular disease management and specialize in minimally invasive treatments. Visit www.SIRfoundation.

Source: Maryann Verrillo

Society of Interventional Radiology

Society For Vascular Surgery Launches New Vascular Quality Inititiative

The Society for Vascular Surgery® (SVS) announced a new quality initiative to improve the care of patients with vascular disease. The Vascular Quality Improvement Initiative includes a registry and regional study groups to analyze the data collected from the registry. The initiative expands SVS’ focus on clinical outcomes and benchmarked reporting. SVS is partnering with M2S on this project which was originally established by the Vascular Study Group of New England.

“The Vascular Quality Improvement Initiative enhances SVS’ mission to assist its members in understanding and improving patient outcomes by encouraging the collection, aggregation, and analysis of clinical data,” said Robert Zwolak, SVS president. “Through this partnership, SVS oversees the electronic registry and manages the Patient Safety Organization. This organization has oversight from a scientific advisory board comprised of SVS and regional group representatives, with Jack Conenwett, MD, Dartmouth-Hitchcock Medical Center and former SVS president, serving as its medical director. M2S provides the web-based registry platform for data collection and analysis.”

The partnership with M2S positions SVS as the leader in vascular outcomes tracking by providing a platform for its members to analyze outcomes, reinforce best practices, and share quality improvement efforts across regions. Currently the Vascular Quality Improvement Initiative has 30 centers across 11 states and Canada. In addition to the 20 institutions in the New England regional group, there are two new regional study groups in the Carolinas, led by Jeb Hallett, MD of Roper St. Francis, and in Texas, led by Mark Davies, MD at Methodist Hospital, Houston. Additional groups are forming in Florida, California, New Jersey, Georgia, Pennsylvania, and Michigan.

“We are excited to partner with SVS to provide the platform for the Vascular Quality Initiative. M2S has been committed to improving vascular patient outcomes for over ten years with our advanced imaging technology. We believe the Vascular Quality Initiative, combined with standardized pre-operative and post-operative imaging, will significantly improve patient care,” said Greg Lange, president and chief operating officer of M2S.

The Vascular Quality Improvement Initiative utilizes MDS’s secure, web-based system, Clinical Data Pathways, for data entry and report generation. Through Clinical Data Pathways participants generate real-time benchmarked reports on six vascular procedures for major outcomes and processes of care to allow for the continuous assessment of them compared to a blinded group of peers based on key performance measures.

Source: Society for Vascular Surgery

A Nomogram Predicting 10-Year Life Expectancy In Candidates For Radical Prostatectomy Or Radiotherapy For Prostate Cancer

UroToday – Family Physicians Could Help in Predicting Life Expectancy without Prostate Cancer.

In the online version of the Journal of Clinical Oncology, Dr. Ravinder Mohan, Department of Family and Community Medicine, Eastern Virginia Medical School has published an interesting correspondence regarding the role for primary care physicians in determining care for patients diagnosed with prostate cancer (CaP).

Dr. Mohan corresponds regarding an article by Walz et al. (J Clin Oncol 2007;25:3576-81) who published a 10-year life expectancy nomogram in candidates undergoing radical prostatectomy or radiotherapy for CaP. That article was followed by an editorial by Ross and Kantoff who question “How many nomograms do we need?” (J Clin Oncol 2007;25:3563-64). Dr. Mohan writes that patients are diagnosed with CaP by the urologist, who has performed the biopsy. They then get counseled by the urologist and possibly a radiation oncologist regarding therapy. In perhaps one visit, the large array of implications of treatment and side effects along with an assessment of the patient’s comorbidities is undertaken. Most commonly, the decision about whether to treat, along with the type of treatment, is finalized before the patient ever returns to the primary care physician. Dr. Mohan agrees that the urologist is best versed in the outcome predictors that should guide treatment options. However, he points out that 40 published nomograms indicate that urologists are not able to better predict optimal treatment. This is because the statistical differences in outcomes are marginal. He cites the fact that the treatment choice may add 3 years or less of quality-adjusted life.

What are needed according to Dr. Mohan are nomograms that better estimate the patient’s health-adjusted life expectancy (HALE). Then, as a second step CaP outcomes nomograms could more accurately predict how CaP or treatment could influence survival. While the American Cancer Society and American Urological Association already require an estimate of the patient’s HALE as a first step, an empiric HALE performed by urologists or medical oncologists is poor, as described by Walz. While Walz points out the need for HALE assessment, their nomogram compares only the risk of CaP mortality to non-cancer factors. Mohan points out that the calculation of HALE is cumbersome, as it requires the scoring of comorbidities followed by a calculation of the effect of comorbidity on life expectancy. Walz has already published that life-tables alone are inaccurate predictors of life expectancy in these patients.

In a study of community patients 70 years or older, two-thirds did not think their primary care physician could predict their life expectancy accurately. However, the majority of these patients desired a discussion about life expectancy. A dedicated visit to the primary care physician, argues Dr. Mohan, could focus on a patient’s health records, habits, comorbidities and quality of life to predict 10-year survival. This could also provide an opportunity for the primary physician who knows the patient best to engage in the decision and determine that the patient is competent, well informed and free from decision bias or coercion. These approaches would benefit patient decision making and are extremely valid suggestions for urologists to implement.

Walz J, Gallina A, Saad F, Montorsi F, Perrotte P, Shariat SF, Jeldres C, Graefen M, BГ©nard F, McCormack M, Valiquette L, Karakiewicz PI.

J Clin Oncol. 2007 Aug 20;25(24):3576-81
doi: 10.1200/JCO.2006.10.3820

Reported by UroToday Contributing Editor Christopher P. Evans, MD, FACS

UroToday – the only urology website with original content global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:

Copyright © 2008 – UroToday

DNA Repair Enzyme Probed By Researchers

Researchers have taken the first steps toward understanding how an enzyme repairs DNA.

Enzymes called helicases play a key role in human health, according to Maria Spies, a University of Illinois biochemistry professor.

“DNA helicases act as critical components in many molecular machineries orchestrating DNA repair in the cell.” she said. “Multiple diseases including cancer and aging are associated with malfunctions in these enzymes.”

Spies’ laboratory undertook a recent study of an enzyme, called Rad3, which defines a group of DNA helicases characterized by a unique structural domain containing iron. The findings appear in the Journal of Biological Chemistry.

Helicases are a special category of molecular motors that modify DNA (deoxyribonucleic acid, the fundamental building block of genes and chromosomes). They do so by moving along strands of DNA, much the same way cars move on roads, using an energy-packed molecule, adenosine triphosphate (ATP) as a fuel source.

Their primary function is to unzip double-stranded DNA, allowing replication and repair of the strands.

DNA is a fragile molecule that undergoes dramatic changes when exposed to radiation, ultraviolet light, toxic chemicals or byproducts of normal cellular processes. DNA damage, if not repaired in time, may lead to mutations, cancer or cell death. Many helicases in the Rad3 family are key players in the cell’s elaborate machinery to prevent and repair such damage. Mutations in the human members of this helicase family impede DNA repair and may contribute to breast cancer, Fanconi Anemia and Xeroderma pigmentosum.

The researchers studied the archaeal version of Rad3. Archaea are microbes whose DNA repair systems are closely related to those of human cells.

“(The archaeal Rad3) is a very good representative of a unique family of structurally related DNA repair helicases, all of which have the same motor core and share an unprecedented (for helicases) structural feature – an accessory domain stabilized by an iron-sulfur cluster,” Spies said.

Working with archaea has the advantage of allowing the researchers to increase the amount available protein and also permits easy genetic manipulation.

Like other helicases, Rad3 is composed of a chain of amino acids. It also contains an ancient prosthetic group called an iron-sulfur cluster, an assembly of four iron and four sulfur atoms incorporated into the protein structure through interaction with four cysteine residues of the amino acid chain.

“DNA helicases, which belong to the Rad3 family, have an auxiliary domain inserted within a conserved motor core. The structure of this domain is stabilized by an iron-sulfur cluster, whose integrity seems to be essential for proper function of these enzymes in DNA repair,” Spies said. By mutating the cysteine ligands to the cluster, the researchers probed its role in the molecular mechanism of Rad3 enzymes. Some of these mutations uncoupled DNA translocation and ATP hydrolysis, meaning that the engine of the protein could still use the ATP fuel but was no longer capable of moving along the DNA.

This analysis also revealed that the integrity of the cluster and the iron-containing domain is crucial for recognition of specific DNA structures believed to be physiological targets for this helicase. “On making these mutations, the helicase no longer behaves like it’s supposed to,” said graduate student Robert Pugh, lead author on the study. “The cluster is still there but the environment around it is somehow changing.”


This research was performed in collaboration with Isaac Caan’s group from Animal Sciences whose lab is engaged in the study of nucleotide metabolism in archaea.

Source: Diana Yates

University of Illinois at Urbana-Champaign