<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_452"
                     title="Study Backs Late Cardiotoxicity of Childhood Cancer Treatment (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/18384?impressionId=1265781311951"
                     
      A childhood cancer survivor&apos;s risk of dying from cardiovascular causes rises with the dose of radiation his heart received during treatment, researchers in France and the U.K. affirmed.&lt;br&gt;
&lt;br&gt;Those whose hearts were exposed had a 60% higher risk of cardiovascular death than the general population, even at a dose of 1 Gy (95% CI 20% to 250%), according to Florent de Vathaire, PhD, of L&apos;Institut National de la Sant&amp;#233; et de la Recherche M&amp;#233;dicale in Paris, and colleagues.&lt;br&gt;
&lt;br&gt;The risk jumped to 12.5-fold for a cumulative radiation dose to the heart of 5 to 14.9 Gy, and to 14.9-fold for a dose of more than 15 Gy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 for trend), the researchers reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The notion that exposing the heart to radiation increases the risk of cardiovascular disease and death is not surprising, according to an accompanying editorial.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;However, this study examined cardiovascular mortality effects of both the dose of radiation and the dose of anthracyclines given to childhood cancer victims in the same cohort.&lt;/p&gt;
&lt;p&gt;That&apos;s something previous studies haven&apos;t done, according to editorialists Steven E. Lipshultz, MD, of the University of Miami and Holtz Children&apos;s Hospital in Miami, and M. Jacob Adams, MD, MPH, of the University of Rochester, N.Y.&lt;/p&gt;
&lt;p&gt;&quot;These are pretty profound findings,&quot; Lipshultz told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;These are the exact concerns we&apos;ve had based on careful subclinical assessments of how the heart in these survivors has been working.&quot;&lt;/p&gt;
&lt;p&gt;His group was one of the first to report that survivors of childhood cancer faced not only acute cardiotoxicity from treatment, but also late cardiac effects.&lt;/p&gt;
&lt;p&gt;As more effective treatment for childhood cancers came into play, the dramatic jump in survival rates  --  from less than 50% in the mid-1970s to 80% today  --  yielded a large enough population of survivors to make chronic issues from treatment apparent, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;&quot;It appears that for some of these survivors we have substituted one fatal disease of childhood  --  cancer  --  for another fatal disease of early adult life,&quot; he said.&lt;/p&gt;
&lt;p&gt;de Vathaire&apos;s group studied a cohort of 4,122 French and British children diagnosed with childhood solid cancer between 1942 and 1986 and who survived at least five years.&lt;/p&gt;
&lt;p&gt;Over an average of 27 years of follow-up, they were at 8.3-fold higher risk of dying from any cause compared with the general populations in France and the U.K. (95% CI 7.6 to 9.0).&lt;/p&gt;
&lt;p&gt;The majority of these excess deaths occurred early after diagnosis, five to nine years afterward in this analysis  --  in which all patients survived to five years.&lt;/p&gt;
&lt;p&gt;Based on just 32 deaths from cardiovascular diseases in the cohort, the childhood cancer survivors experienced five times the cardiovascular mortality (95% CI 3.3 to 6.7) expected from the general population (1.7% cumulative at 35 years versus 0.3%).&lt;/p&gt;
&lt;p&gt;This elevation in risk was similar to that seen in large studies from the U.S. and Nordic countries, suggesting generalizability of the results, Lipshultz said.&lt;/p&gt;
&lt;p&gt;Radiation therapy also conferred a 5.0-fold elevation in risk of cardiovascular disease-related death (95% CI 1.2 to 21.4).&lt;/p&gt;
&lt;p&gt;Like radiation, a higher cumulative dose of anthracycline chemotherapy also increased risk of dying from cardiac diseases, compared with the general population (RR 4.4 for a dose over 360 mg/m&lt;sup&gt;2&lt;/sup&gt;, 95% CI 1.3 to 15.3).&lt;/p&gt;
&lt;p&gt;However, radiotherapy and chemotherapy did not appear to interact for cardiovascular mortality (&lt;em&gt;P&lt;/em&gt;=0.4).&lt;/p&gt;
&lt;p&gt;Notably, the vinca alkaloids were also significantly linked to cardiovascular disease-related death risk among childhood cancer survivors, even after adjustment for sex, treatment period, age at diagnosis, follow-up, and all other treatment modalities (RR 3.6, 95% CI 1.0 to 12.9).&lt;/p&gt;
&lt;p&gt;Currently, guidelines support regular long-term cardiovascular screening for childhood cancer survivors who received anthracycline-based chemotherapy but provide little to no direction for those treated with nonanthracycline chemotherapy or radiation, Lipshultz noted.&lt;/p&gt;
&lt;p&gt;These results suggested all three groups should be getting cardiac follow-up, he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;However, because other research has suggested that these individual treatments affect the heart in different ways, such as diastolic rather than systolic dysfunction with radiotherapy, screening modalities may need to account for this as well, he said.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that cardiovascular disease was probably under-reported as a cause of death in the cohort.&lt;/p&gt;
&lt;p&gt;&quot;Indeed, 15 of the deaths classified as results of cancer as the principal cause had cardiovascular diseases as the immediate cause,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the Ligue Nationale Contre le Cancer; the Programme Hospitalier de Recherche Clinique; the Agence Fran&amp;#231;aise de S&amp;#233;curit&amp;#233; Sanitaire et Produit de Sant&amp;#233;; Electricit&amp;#233; de France; the Wyeth Foundation for childhood and adolescent health; and a grant from the Foundation of France.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;The editorialists reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_400"
                     title="Fractured Evidence: Spine Repair Debate Heats Up"
                     score="0.009"
                     href="http://www.medpagetoday.com/Surgery/Orthopedics/tb/18303?impressionId=1265781311951"
                     
      &lt;p&gt;Hundreds of thousands have benefited from vertebroplasty, advocates insist. They say the minimally-invasive procedure has freed them from hospital beds and dependence on intravenous narcotics.&lt;/p&gt;
&lt;p&gt;Spine physicians swear that inserting a large-gauge needle into fractured vertebrae and injecting a cement compound to stabilize the bone hastens healing and helps relieve the often-crippling pain of compression fractures brought on by osteoporosis or metastatic disease.&lt;/p&gt;
&lt;p&gt;But two recently-published, randomized controlled trials  --  the gold standard of evidence-based medicine  --  say otherwise. As far as disability and pain relief were concerned, they found that vertebroplasty for osteoporotic vertebral compression fractures was no better than a sham procedure.&lt;/p&gt;
&lt;p&gt;Publication of the results triggered an outraged backlash from radiologists, for whom vertebroplasty is a bread-and-butter operation. The entire specialist community lambasted the studies  --  statistically and methodologically.&lt;/p&gt;
&lt;p&gt;But experts in evidence-based medicine argue that when profits are on the line, it&apos;s easy to be persuaded that studies are flawed.&lt;/p&gt;
&lt;p&gt;So the debate rages, with radiologists citing case after case of success, arguing that patients with the worst fractures will have no treatment alternatives if the nation&apos;s third-party payers  --  Medicare and the insurance companies&lt;strong&gt; -&lt;/strong&gt;- refuse to pay for the procedure anymore.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;The Studies&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Both randomized, controlled studies were published last August in the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;. They involved a combined total of about 200 patients. Each found that vertebroplasty did not yield significantly better results in terms of disability or short-term pain relief than sham procedures for patients with this type of vertebral fracture.&lt;/p&gt;
&lt;p&gt;In an e-mail to &lt;em&gt;MedPage Today&lt;/em&gt;, the author of one study, Rachelle Buchbinder, PhD, of Monash University in Australia, suggested that the research showed the procedure was ineffective.&lt;/p&gt;
&lt;p&gt;&quot;Based upon the results of both trials I don&apos;t think that this treatment should be offered in routine care,&quot; she declared.&lt;/p&gt;
&lt;p&gt;But the leader of the other trial, David Kallmes, MD, of the Mayo Clinic in Rochester, Minn., offered a different interpretation. He said the studies have been largely misunderstood by the trials&apos; critics&lt;strong&gt;.&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;&quot;I&apos;ve been practicing for 15 years and had strong confidence that the procedure was effective, and that&apos;s exactly what we showed,&quot; he said in a telephone interview.&lt;/p&gt;
&lt;p&gt;Mean baseline pain intensity on a 10-point scale was 6.9 in the vertebroplasty group and 7.2 in the sham-operated group in his trial, which had 131 patients. One month later, these scores had declined to 3.9 and 4.6, respectively.&lt;/p&gt;
&lt;p&gt;Kallmes said this degree of pain reduction with vertebroplasty &quot;exactly reproduces our prior experience.&quot; He vehemently denied that the findings were &quot;discordant&quot; with prior experience, as two statements from the Society of Interventional Radiology (SIR) put it.&lt;/p&gt;
&lt;p&gt;&quot;I don&apos;t know what they&apos;re talking about,&quot; Kallmes said. &quot;It is concordant.&quot;&lt;/p&gt;
&lt;p&gt;He said the real surprise was the effectiveness of the sham procedure, which should be the focus of follow-up investigations.&lt;/p&gt;
&lt;p&gt;It involved inserting needles into the spinal column and injecting short-acting painkillers such as lidocaine, as was also done with vertebroplasty prior to inserting needles into the fractured vertebrae and injecting the cement.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;The Flaws&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Critics of the two studies cite a laundry list of complaints: too few patients, failure to meet enrollment, inclusion of patients with milder degrees of pain and disability than those usually treated.&lt;/p&gt;
&lt;p&gt;In a November commentary from SIR, issued in conjunction with &lt;em&gt;NEJM&apos;s &lt;/em&gt;publication of letters critical of the studies, J. Kevin McGraw, MD, of Riverside Radiology and Interventional Associates in Columbus, Ohio, highlighted the fact that Kallmes&apos; study originally called for 250 patients.&lt;/p&gt;
&lt;p&gt;Only 131 enrolled, and the vast majority  --  1,682 of 1,813 screened  --  were excluded, &quot;introducing significant selection bias into the study,&quot; he complained.&lt;/p&gt;
&lt;p&gt;McGraw also pointed out that Kallmes&apos; group didn&apos;t use screening MRI to ensure that a fracture was the cause of the patient&apos;s pain.&lt;/p&gt;
&lt;p&gt;In addition, he did some additional statistical noodling and found that if one additional patient had reported a favorable response in the vertebroplasty group, the &lt;em&gt;P&lt;/em&gt;-value would be 0.04, rather than a nonsignificant 0.06. Likewise, if one more patient had an unfavorable response in control group, the association&apos;s&lt;em&gt; P&lt;/em&gt;-value would become significant.&lt;/p&gt;
&lt;p&gt;Finally, in the crossover part of the trial, McGraw highlighted that 12% of patients in the vertebroplasty arm elected the sham procedure, while 43% of those who got the sham went for the real thing.&lt;/p&gt;
&lt;p&gt;&quot;The tremendous crossover rate speaks for some obvious benefit of vertebroplasty over sham and is worthy of a future adequately powered analysis to evaluate,&quot; McGraw wrote.&lt;/p&gt;
&lt;p&gt;As for the Buchbinder trial, McGraw said it was convoluted by selection bias, since two-thirds of patients came from a single center and their procedures were performed by a single radiologist. The commentary also criticizes the volume of cement injected into vertebrae as lower than normal.&lt;/p&gt;
&lt;p&gt;Similarly, the North American Spine Society issued a critique of patient selection criteria and outcome measures, and questioned whether the sham treatment was actually an active therapy. The statement suggested that dry needling might be a more appropriate control.&lt;/p&gt;
&lt;p&gt;One of the letters published in &lt;em&gt;NEJM&lt;/em&gt; also criticized the protocol requirement that patients undergo four weeks of medical therapy prior to enrollment in the trial. During that time, some fractures would have already healed, &quot;resulting in a study on healed fractures,&quot; a group of Australian physicians wrote.&lt;/p&gt;
&lt;p&gt;SIR president Brian F. Stainken, MD, took issue with the fact that patients with the most pain  --  typically older, osteoporotic women  --  weren&apos;t represented.&lt;/p&gt;
&lt;p&gt;McGraw said these patients would be the least likely to agree to be in a randomized trial with a 50% chance of receiving the sham treatment.&lt;/p&gt;
&lt;p&gt;&quot;Most people in severe pain won&apos;t enroll,&quot; Stainken said. &quot;At some level, research design has to take reality into consideration.&quot;&lt;/p&gt;
&lt;p&gt;&quot;The population with low-grade pain, that&apos;s the population these papers focused on,&quot; he continued. &quot;It&apos;s not clear what the right solution is for this group. But I think the contribution of these [two &lt;em&gt;NEJM&lt;/em&gt; studies] may be toward that.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;On the Defense&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Kallmes, however, responded that there was no difference in baseline pain scores between patients entering the study and those considered eligible but refusing to participate.&lt;/p&gt;
&lt;p&gt;He also told &lt;em&gt;MedPage Today&lt;/em&gt; that he and colleagues &quot;enrolled patients that are very similar to those treated around the world.&quot;&lt;/p&gt;
&lt;p&gt;&quot;These studies were by far, by far, the best studies ever done,&quot; Kallmes declared.&lt;/p&gt;
&lt;p&gt;&quot;I have full confidence that if we had shown something different, that is, if we had found the procedure was more effective than placebo, people would have embraced it and said they were great studies,&quot; he continued.&lt;/p&gt;
&lt;p&gt;&quot;They would have said, &apos;Look at it, they were prospective, randomized, blinded, near 100% follow-up.&apos; They would have been held up as the paragon for how to do studies in the future  --  if we had reinforced people&apos;s preconceived notions.&quot;&lt;/p&gt;
&lt;p&gt;Richard Deyo, MD, MPH, professor of evidence-based medicine at Oregon Health &amp;amp; Science University in Portland and deputy editor of &lt;em&gt;Spine,&lt;/em&gt; told &lt;em&gt;MedPage Today&lt;/em&gt; that the studies are the best evidence to date regarding the effectiveness of vertebroplasty in these patients.&lt;/p&gt;
&lt;p&gt;&quot;No study is perfect, and these are not perfect, but I do think they&apos;re the best we have,&quot; Deyo said.&lt;/p&gt;
&lt;p&gt;Deyo said there was some validity to complaints that the studies enrolled too few patients, although both trials were adequately powered to detect a difference in pain reduction.&lt;/p&gt;
&lt;p&gt;&quot;If the benefit of this treatment were as enormous as many of the advocates argue,&quot; he said, &quot;then it would take a much smaller study to demonstrate a huge benefit.&quot;&lt;/p&gt;
&lt;p&gt;On the other hand, the studies were too small to evaluate the effects among various patient subgroups.&lt;/p&gt;
&lt;p&gt;Kallmes also criticized the societies&apos; press releases, charging they were written by some &quot;who haven&apos;t read the studies carefully.&quot;&lt;/p&gt;
&lt;p&gt;&quot;The societies are in a great position,&quot; he said. &quot;They have thought leaders that they can partner with to move the science forward. Moving the science forward is not done by sending out press releases.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Radiologists&apos; Concerns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;SIR&apos;s reaction may not be surprising, given that radiologists are so vested in vertebroplasty. Medicare will pay physicians from $522 to $554 for a procedure on one vertebra performed in a hospital or outpatient surgery clinic  --  or more than $2,000 if it&apos;s conducted in the physician&apos;s office.&lt;/p&gt;
&lt;p&gt;The number of annual procedures varies from office to office, and radiologists provide varying estimates. McGraw said he performs about 150 vertebroplasties annually, and Stainken said the procedure accounts for about 20% of radiologists&apos; procedures, although that estimate &quot;may be a little high.&quot;&lt;/p&gt;

&lt;p&gt;One of the radiologists&apos; main concerns is that insurance companies will use the trials to justify ending coverage of vertebroplasty for osteoporotic spinal fractures.&lt;/p&gt;
&lt;p&gt;But insurers started playing that card long before the &lt;em&gt;NEJM&lt;/em&gt; trials were published.&lt;/p&gt;
&lt;p&gt;In a 2008 report, the Technology Evaluation Center of the Blue Cross and Blue Shield Association (BCBSA) concluded that neither vertebroplasty nor the related kyphoplasty  --  which restores compression-fractured vertebrae to their normal size with a balloon before the cement injection  --  had been demonstrated to be any better at improving net health outcomes than medical treatments.&lt;/p&gt;
&lt;p&gt;That same year, Wellpoint, the insurance giant with 35 million members, announced plans to classify both procedures &quot;investigational.&quot; That prompted a letter from SIR imploring the company to reconsider.&lt;/p&gt;
&lt;p&gt;Another spine physician, Christopher Bono, MD, of Brigham &amp;amp; Women&apos;s Hospital in Boston, told &lt;em&gt;MedPage Today &lt;/em&gt;that Aetna was also reconsidering coverage for vertebroplasty following the &lt;em&gt;NEJM&lt;/em&gt; publications.&lt;/p&gt;

&lt;p&gt;He said that he believed the firms would not end coverage entirely, but policies would be more restrictive.&lt;/p&gt;
&lt;p&gt;&quot;My gut sense is that payers are going to be much more selective in who they will pay for [regarding vertebroplasty],&quot; Bono said. &quot;They will ask for certain documentation and many more criteria than they did in the past.&quot;&lt;/p&gt;
&lt;p&gt;McGraw worries that seniors will be &quot;denied coverage when they are in the twilight of their lives and could possibly have long-standing suffering&quot; that &quot;could lead to their demise.&quot;&lt;/p&gt;
&lt;p&gt;Stainken said there&apos;s &quot;clear, unambiguous data that prolonged bed rest is the beginning of the cycle of decline for these patients. The key is to be able to do everything we can to ... keep these patients ambulatory and avoid that whole scenario.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Change is Hard&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Deyo said money may partly explain the reluctance of physicians who perform vertebroplasties to scale back their use of the procedure.&lt;/p&gt;
&lt;p&gt;&quot;There are people who are making a living doing this, and you don&apos;t easily change what you do for a living,&quot; Deyo said.&lt;/p&gt;
&lt;p&gt;The man credited with coining the term &quot;evidence-based medicine&quot; agreed.&lt;/p&gt;
&lt;p&gt;&quot;If you are making money from a procedure, it is very easy to persuade yourself that new evidence that the procedure is ineffective is in some way flawed or limited to allow you to continue to make money on the procedure,&quot; Gordon Guyatt, MD, of McMaster University in Hamilton, Ontario, told &lt;em&gt;MedPage Today.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&quot;When we have opinions and beliefs, we are very resistant to new evidence.&quot;&lt;/p&gt;
&lt;p&gt;Kallmes, too, said there are psychological reasons for not accepting the results: &quot;People just don&apos;t want to be convinced. They don&apos;t want to change their preconceived notions.&quot;&lt;/p&gt;
&lt;p&gt;&quot;They have this anecdotal experience,&quot; he added, &quot;but I can tell them anecdotes of miraculous results with the placebo. So if they do this same study themselves, they may find the same thing I found.&quot;&lt;/p&gt;
&lt;p&gt;Still, McGraw and Bono insisted the studies were too flawed to serve as the evidence base for clinical practice.&lt;/p&gt;
&lt;p&gt;&quot;Before we make these two studies the Holy Grail of evidentiary medicine with regard to vertebroplasty, we need to have larger trials,&quot; McGraw said.&lt;/p&gt;
&lt;p&gt;Bono said evidence-based medicine, properly implemented, has three components: reviewing and applying the best data, &quot;but also incorporating surgeon experience and patient preference.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If you are just using the first, and I&apos;m a strong advocate for using data and literature and references, I think you&apos;re doing a disservice,&quot; he said. &quot;And then if you are misinterpreting the data or twisting the data or slanting the data, and eliminating the other two, you are really abusing the word evidence-based medicine.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Outcomes&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;So, will vertebroplasty go the way of other procedures that seemed to work clinically, but bombed in trials, such as knee arthroscopy for osteoarthritis?&lt;/p&gt;
&lt;p&gt;SIR is awaiting the results of VERTOS II, a 200-patient Dutch trial comparing vertebroplasty with conservative therapy in patients with painful, osteoporotic vertebral compression fractures. And Stainken called for large trials that will address several of the methodology issues raised with the &lt;em&gt;NEJM &lt;/em&gt;reports.&lt;/p&gt;
&lt;p&gt;With regard to the potential placebo effect, Kallmes said he has nearly completed a 20-patient, open-label study of a procedure like that used as the sham in the randomized trial  --  a spinal injection of short-acting painkillers.&lt;/p&gt;
&lt;p&gt;Also in the works is a comparative trial of vertebroplasty and balloon kyphoplasty, he said.&lt;/p&gt;
&lt;p&gt;Stainken said he has heard from colleagues who said they had slowed down or stopped doing the procedures after the studies were published, &quot;which is not unreasonable  --  to think it through and understand the situation.&quot;&lt;/p&gt;
&lt;p&gt;However, most have resumed performing the procedure, and demand for it continues, he added.&lt;/p&gt;
&lt;p&gt;Aman Patel, MD, an associate professor of radiology and neurosurgery at Mount Sinai School of Medicine in New York City, said he and his colleagues have not changed their practice since learning of the studies&apos; findings.&lt;/p&gt;
&lt;p&gt;However, he has started telling patients about the findings from the &lt;em&gt;NEJM&lt;/em&gt; studies so they can be fully informed of the existing evidence about the risks and benefits of vertebroplasty.&lt;/p&gt;
&lt;p&gt;&quot;I firmly believe this procedure benefits some, if not many, patients,&quot; Patel said.&lt;/p&gt;
&lt;p&gt;McGraw said he tells patients about the trials, but he also tells patients who he thinks would benefit from vertebroplasty that he doesn&apos;t believe the findings apply to them.&lt;/p&gt;
&lt;p&gt;He said one patient had initially declined the procedure after talking it over. &quot;That patient called me up a week later to proceed with vertebroplasty,&quot; he said.&lt;/p&gt;
&lt;p&gt;Even if the findings don&apos;t change the way spine doctors use vertebroplasty in the short term, Deyo suspects the results will lead to fewer procedures in the long run.&lt;/p&gt;
&lt;p&gt;Guyatt and Deyo predicted that eventually, a critical mass of evidence would be assembled  --  assuming future randomized studies replicate these results  --  that would convince even the most steadfast adherents.&lt;/p&gt;
&lt;p&gt;Also, the &lt;em&gt;NEJM&lt;/em&gt; studies could have an immediate effect in promoting more research by increasing the level of doubt about the procedure, Deyo said: &quot;I don&apos;t think we have the final word here.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Deyo, Guyatt, Patel, and Stainken reported having no relevant conflicts of interest.&lt;/p&gt;&lt;p&gt;Bono reported financial relationships other than research funding with Life Spine, Depuy, Medtronic, and Stryker, and research funding from Archus Orthopedics and Synthes Spine. He was lead author of the North American Spine Society&apos;s critique of the two randomized trials published in the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.&lt;/p&gt;&lt;p&gt;McGraw has had relationships with Cardinal Spine, Arthrocare Spine, and Hatch Medical.&lt;/p&gt;&lt;p&gt;Kallmes reported relationships with ArthroCare, Stryker, Cardinal, and Cook.&lt;/p&gt;&lt;p&gt;Buchbinder reported receiving research funding from Cook.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_318"
                     title="Preop CT May Reduce Unnecessary Appendectomy (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/Surgery/GeneralSurgery/tb/18185?impressionId=1265781311951"
                     
      Using computed tomography (CT) to diagnose appendicitis may reduce the likelihood of removing healthy organs in women under 45, but not among other groups, a retrospective study showed.&lt;br&gt;
&lt;br&gt;Over a 10-year period, the use of preoperative CT increased from 18.5% of patients who ultimately had their appendices removed to 94.2% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.00001), according to Courtney Coursey, MD, of Duke University Medical Centeri, and colleagues.&lt;br&gt;
&lt;br&gt;During the same time period, the rate of negative appendectomy (removal of a healthy organ) declined, although the trend was significant only among women 45 and younger (&lt;em&gt;P&lt;/em&gt;=0.0001), the researchers reported in the February issue of &lt;em&gt;Radiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;We believe our study . . . supports the use of preoperative CT, particularly in the evaluation of women of reproductive age suspected of having acute appendicitis,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;They acknowledged the radiation risk and potential overuse of CT scans, but concluded, &quot;We believe that the risk of unnecessary surgery justifies the use of CT in patients in whom the clinical diagnosis of appendicitis is uncertain.&quot;&lt;/p&gt;
&lt;p&gt;Previous studies looking at the link between the use of preoperative CT and the negative appendectomy rate have yielded mixed results.&lt;/p&gt;
&lt;p&gt;So Coursey and her colleagues looked at the relationship using data from 1998 to 2007 for 925 adult patients who underwent an appendectomy at Duke. Two-thirds had a preoperative CT no more than 48 hours before surgery.&lt;/p&gt;
&lt;p&gt;Although the overall negative appendectomy fell by nearly half during the study (16.7% to 8.7%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), it was driven almost entirely by a reduction among women 45 and younger (42.9% to 7.1%, &lt;em&gt;P&lt;/em&gt;=0.0001).&lt;/p&gt;
&lt;p&gt;&quot;However, the timing of the decline in negative appendectomy rates for women 45 years and younger could not be proved to be associated with the increase in CT use,&quot; the researchers noted.&lt;/p&gt;
&lt;p&gt;There were no significant trends in older women or in men of any age.&lt;/p&gt;
&lt;p&gt;&quot;The lack of a decline in the negative appendectomy rates for men and women older than 45 years may be a consequence of the initially low rates resulting in low power,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;During the study, false-negative CT scans ranged from 0% to 20%, with lower rates in the later years of the study.&lt;/p&gt;
&lt;p&gt;False-positive scans fluctuated between 1.7% to 10%. A drop in rates of false-positive scans was associated with advances in CT technology.&lt;/p&gt;
&lt;p&gt;The researchers noted some limitations of the study, including the retrospective design and the failure to evaluate the effect of CT detector configuration on diagnostic performance.&lt;/p&gt;
&lt;p&gt;In addition, they wrote, the measure of CT use to diagnose appendicitis was biased because the analysis excluded cases in which CT had ruled out appendicitis.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;One of Coursey&apos;s co-authors is a consultant to GE Healthcare.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_242"
                     title="Ultrasound Aids Early Ovarian Cancer Detection (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/Radiology/DiagnosticRadiology/tb/18096?impressionId=1265781311951"
                     
      &lt;p&gt;Serum biomarkers identified through proteomic analysis, coupled with contrast-enhanced ultrasound, ultimately may provide a means for early diagnosis of ovarian cancer, researchers say.&lt;/p&gt;
&lt;p&gt;&quot;Exciting preliminary data have shown that specific combinations of peptides from molecules, such as &lt;em&gt;BRCA2&lt;/em&gt;, exist in the serum of epithelial ovarian cancer patients,&quot; Sonia Dutta, MD, of Mount Sinai School of Medicine in New York, and colleagues reported in the February&lt;em&gt; American Journal of Roentgenology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;This discovery suggests that &quot;highly discriminatory proteins&quot; may serve as biomarkers for early epithelial cell ovarian cancer, although the findings must be further validated, the authors wrote.&lt;/p&gt;
&lt;p&gt;Despite advances in surgery and chemotherapy, survival from advanced stage ovarian cancer is only 30%, and the authors cite a &quot;dire need&quot; for a validated screening method to detect the disease early.&lt;/p&gt;
&lt;p&gt;Unsuccessful efforts find a biomarker for this deadly malignancy have focused primarily on a single cancer-specific marker, which the authors concede is a &quot;mission impossible.&quot;&lt;/p&gt;
&lt;p&gt;Impediments to the identification of cancer-specific markers include the molecular heterogeneity that characterizes different tumors, the sharing of pathophysiologic events among cancer and other diseases, and low marker production and concentration.&lt;/p&gt;
&lt;p&gt;To overcome these difficulties, a new approach known as proteomics is being used to analyze the entire protein complement of a cell.&lt;/p&gt;
&lt;p&gt;The rationale for this analytical technique lies in a significantly greater understanding of the tumor microenvironment. It is now known that tumor cells participate in complex interactions with surrounding structures and other cell populations.&lt;/p&gt;
&lt;p&gt;&quot;This biochemical cross-talk is hypothesized to generate a cascade of specific and sensitive biomarkers elaborated directly from the tumor cell population, indirectly from the interacting non-tumor cells or extracellular molecules, or a specific product of the microecology,&quot; they explained.&lt;/p&gt;
&lt;p&gt;In fact, the most specific cancer markers may turn out to be molecules that normally are not malignant but that have been modified by that tumor microenvironment  --  clipped, cleaved, phosphorylated, or glycosylated  --  and carry a detailed picture of the local pathophysiology.&lt;/p&gt;
&lt;p&gt;Previous techniques used in the hunt for markers, such as two-dimensional gel electrophoresis, were unable to detect these altered or clipped molecules, which occupy the low molecular weight range of the proteome.&lt;/p&gt;
&lt;p&gt;Mass spectrometry, which is most sensitive in the low molecular weight range, is now a tool used to explore these modified protein molecules and has already revealed a vast number of previously unknown biomarkers.&lt;/p&gt;
&lt;p&gt;The next steps, the researchers explained, will be to develop capture reagents that can measure the markers and, using reverse-phase protein array, to further characterize proteins of interest.&lt;/p&gt;
&lt;p&gt;But any diagnostic information gained through proteomic analysis must be verified by some imaging technique. Conventional ultrasound has proven inadequate, but pulse-inversion harmonic ultrasound currently appears to differentiate malignant from benign lesions.&lt;/p&gt;
&lt;p&gt;For example, although the time to peak enhancement with contrast-enhanced ultrasound is similar in benign and malignant masses, a small study found that malignant lesions have: &lt;ul&gt; &lt;li&gt;Greater peak enhancement (23.3 versus 12.3 dB, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Longer half wash-out time (139.9 versus 46.3 seconds, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Greater area under the enhancement curve (2,012.9 versus 523.9 seconds, &lt;em&gt;P&lt;/em&gt;=0.07)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The authors noted that these enhancement kinetics data were from just 17 patients and are therefore limited, but stated that the technique &quot;shows great promise.&quot;&lt;/p&gt;
&lt;p&gt;In addition, the diagnostic capacity of ultrasound can be further increased by the use of intravenous contrast agents, which may help visualize the early microvascular changes typical of malignancy.&lt;/p&gt;
&lt;p&gt;The researchers predicted that, by using a combination of clinically relevant biomarkers identified through proteomic analyses plus contrast-enhanced ultrasound, &quot;we will likely be able to shift from an era of diagnosing advanced-stage ovarian cancer to that of early-stage disease and, most important, save the lives of many women.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No disclosures were provided.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_196"
                     title="Adjuvant Therapy Improves Survival in Pancreatic Cancer (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/18039?impressionId=1265781311951"
                     
      &lt;p&gt;Adjuvant chemoradiotherapy significantly improves survival of patients with resectable pancreatic cancer, according to medical records of almost 3,000 patients.&lt;/p&gt;
&lt;p&gt;Chemoradiotherapy extended median survival by more than 30% compared with surgical resection only, researchers reported in the January &lt;em&gt;Archives of Surgery&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&lt;em&gt; &lt;/em&gt;In a multivariate analysis, adjuvant chemoradiotherapy proved to be one of only three predictors of improved survival, the other two being treatment at high-volume and academic centers.&lt;/p&gt;
&lt;p&gt;&quot;This analysis provides strong evidence in a real-world setting that postoperative chemoradiotherapy and possibly adjuvant radiotherapy alone improve clinical outcome in patients with pancreatic cancer,&quot; Relin Yang, MD, of the University of Miami, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;We further substantiate that this benefit is independent of the improved clinical outcomes obtained at high-volume centers and teaching facilities,&quot; they added.&lt;/p&gt;
&lt;p&gt;&quot;Nonetheless, this benefit remains modest, underscoring that further investigation is needed to establish a better adjuvant regimen after complete resection of pancreatic cancer.&quot;&lt;/p&gt;
&lt;p&gt;Complete surgical resection remains the only curative option for patients with early-stage pancreatic adenocarcinoma. Fewer than 25% of patients have cancer amenable to resection. For that small subset of patients, the role of adjuvant therapy remains controversial, the authors wrote.&lt;/p&gt;
&lt;p&gt;To address the issue, Yang and colleagues analyzed data from a population-based cancer registry. They augmented the data&apos;s predictive potential with information related to patient demographics, comorbidities, treatment, and type of facility.&lt;/p&gt;
&lt;p&gt;The authors identified 2,877 patients whose pancreatic adenocarcinoma was diagnosed and treated surgically with curative intent from 1998 to 2002. About 60% of the patients were older than 65. Some 90% were white (86.7% non-Hispanic), and 90% had no history of alcohol abuse.&lt;/p&gt;
&lt;p&gt;The authors reported that 51.9% of patients received neither chemotherapy nor chemoradiotherapy. About 25% received chemoradiotherapy, and another 10% received chemotherapy alone. Most patients were treated at low-volume centers (57.6%) and nonteaching facilities (72.8%).&lt;/p&gt;
&lt;p&gt;Median overall survival was 15 months, and 90-day postsurgical survival was 88.8%. Patients younger than 40 had the best survival (25.7 months versus 13.4 months for patients older than 65, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Race, ethnicity, and abstention from alcohol and tobacco did not significantly influence survival. Survival decreased as a patient&apos;s poverty level increased. Localized disease, well-differentiated tumors, and smaller tumor size were associated with significantly better survival (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Patients treated with surgery only had a significantly lower (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) median overall survival of 12.6 months compared with patients who received chemotherapy or radiation preoperatively (19.9 months) or postoperatively (17.0 months).&lt;/p&gt;
&lt;p&gt;Median survival was 18.2 months among patients treated at high-volume centers versus 13.1 months at low-volume centers (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001). Treatment at a teaching facility was associated with a median survival of 19.8 months compared with 13.6 months for nonteaching facilities (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Multivariate analysis correcting for comorbidities showed that postoperative chemoradiotherapy significantly reduced the mortality hazard ratio (HR 0.69, &lt;em&gt;P&lt;/em&gt;=0.04). The reduced hazard exceeded the benefit associated with treatment at a high-volume center (HR 0.85, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) or at a teaching facility (HR 0.84, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and was independent of facility type.&lt;/p&gt;
&lt;p&gt;The authors confirmed findings from other studies showing a beneficial effect of treatment in high-volume and teaching facilities, and a benefit for all patients who receive adjuvant chemoradiotherapy, Nita Ahuja, MD, of Johns Hopkins, wrote in a commentary.&lt;/p&gt;
&lt;p&gt;However, the study had several prominent weaknesses: missing information on cancer stage in more than 50% of patients, unknown margin status, and no information on the type or duration of adjuvant therapy.&lt;/p&gt;
&lt;p&gt;The study also did not address another major controversy involving adjuvant therapy for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;&quot;At the end of the day, the present study will do little to quell the debate over the relative benefits of adjuvant chemoradiotherapy compared with chemotherapy alone after surgical resection of pancreatic cancer,&quot; Ahuja wrote.&lt;/p&gt;
&lt;p&gt;North Americans have a bias toward adjuvant chemoradiotherapy, supported primarily by data from a single small randomized clinical trial and several retrospective studies, Ahuja continued. European clinicians favor adjuvant chemotherapy based on one large clinical trial showing a benefit for chemotherapy and another showing no survival advantage for chemoradiotherapy.&lt;/p&gt;
&lt;p&gt;&quot;The present study will do little to change the minds of either camp,&quot; Ahuja concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Neither Yang and co-authors nor Ahuja had any disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>