Guideline

"Far too often we are presented with literature that is tainted by significant bias. Authors do not want to show their "dirty laundry".Hence, case series with suboptimal results are often not published, thus skewing the literature. Worse yet, complications may be 'selectively' presented. Complication reporting, particularly with data that is collected retrospectively, is often deficient.

Hence the literature is flawed, in that it may lead one to believe that a treatment strategy (ie, lumbar disc surgery) is associated with a better outcome and fewer complications than truly exists in 'real life'.

Baksh should be applauded for honest reporting. The 'real life' the results reported by Bakhsh are realistic. They do not reflect pessism nor optimism. They indeed are reflective of realism. If our patients choose to undergo surgery with visions of better outcomes, they are being deceived.

We should take this article to heart and make decisions based on real unbiased numbers.Bakhsh is to be heartily congratulated for his honest and enlightening reporting.

I agree with the comments of Doug and Ed.
The study suffers from it's retrospective nature. I get the sense that this is not a consecutive group of patients that meet the inclusion criteria. There are absolutely no validated outcome measures used whatsoever. Evidence level is class III, and weak at that.

Doug has correctly pointed out that the treatment is nonstandard and certainly degrades the long term results. The diagnostic measures, without axial data, make certain identification of the pathology difficult. I recognize that circumstances dictate the preoperative workup.

There is no discussion of intraoperative findings and the correlation to preoperative studies.
No discussion of complications and their correlation to outcomes would be beneficial.

I am surprised at the lack of improvement in any preoperative sensory deficit and the high rate of development of new postoperative deficit. What does this say about the treatment and surgery performed?

It is also unusual that no patient with recurrent symptoms wanted to consider further diagnostic studies and surgery.
Greg

Prof Douglas Orr

I might give it a bit of a different slant though I like your thoughts Ed. The author does not give the denominator. He states that only the 68 pts who responded are studied. If the series contained 70 pts the results are valid. If it contained 700 they are not. In addition he describes a surgical technique that is not what is currently done in most settings. Wide bilateral laminectomy and curretting of the end plates would not be the current standard and this may also bias the end result. Aggressive discectomy may reduce recurrence rate (even this is controversial) but it definitely increases long term incidence of axial back pain. Wide laminectomy especially at 4/5 may increase the incidence of late instability. I applaud Dr Baksh for his reporting of his long term outcomes but I am not sure his and Ed's pessimism in justified.

May 21, 2010 — More pediatric epilepsy patients are becoming seizure free after surgery than ever before, say researchers. They attribute the improvement to better technology, procedures, and changes in clinical practice.

"Patients who have failed 2 or 3 antiepileptic drugs who are MRI [magnetic resonance imaging] positive are very unlikely to respond to medication alone," senior investigator Gary Mathern, MD, from the University of California at Los Angeles, said in an interview

Dr. Mathern is now reporting new data out of UCLA comparing outcomes for 192 pediatric epilepsy patients operated on in the first years of the center's program to those for 379 patients treated in the last decade. The differences between outcomes of young patients who underwent surgery in the early years from 1986 to 1997 compared with more recently were striking. The researchers say that technologies clearly identifying lesions and a new emphasis on complete resection are proving beneficial. The results are scheduled to be published in the June 1 issue of Neurology but are currently available online.

"Parents and referring physicians should not see pediatric epilepsy surgery as a treatment of last resort," coauthor Raman Sankar, MD, from Mattel Children's Hospital at UCLA, said in a news release. "Our experience shows that with earlier and more successful surgery, children can expect a more normal life."

Magnetic resonance images of cerebral hemispherectomy patients seizure free after surgery

Parents and referring physicians should not see pediatric epilepsy surgery as a treatment of last resort.

The numbers are encouraging, but they are based on a retrospective analysis. And although some of the more recent patients have been followed up for 5 years, many have not because they were operated on later in the millennium up to 2008. The researchers acknowledge that they will need to continue monitoring these patients to determine whether the reported outcomes persist.

But this first look suggests that despite similarities in seizure frequency, age at onset, and age at surgery between groups, the more recent patients had more lobar and focal and fewer multilobar resections. More of these patients also had tuberous sclerosis complex and fewer cases of nonspecific gliosis. Most did not undergo intracranial electroencephalogram.

Most notable, perhaps, refractory patients who underwent surgery in recent years were more likely to recover seizure free.

Table. Percentage of Patients Seizure Free After Surgery

More seizure-free patients in recent years were taking medications at each time point but were less likely to be taking drugs 5 years after surgery. They also experienced fewer complications and subsequent operations. Logistic regression identified that less aggressive medication withdrawal was the main predictor of becoming seizure free 2 years after surgery.

UCLA surgeons say the improvement in outcomes for the pediatric patients was likely due to multiple overlapping and interacting factors. They attribute it to better presurgical noninvasive technology to identify lesions, improved selection of potential surgical candidates, and a decision by specialists to completely remove the lesion at surgery and alter postoperative antiepileptic drug management after 1997.

Epilepsy is the Rodney Dangerfield of neurological diseases. It gets no respect.

The researchers suggest that better neuroimaging technologies and experience in using them probably explain the decrease in patients with nonspecific gliosis. They say this likely also explains the increase in the percentage of patients with focal and lobar operations compared with multilobar resections.

"Without surgery, these children are at risk for epileptic encephalopathy and an IQ less than 50," Dr. Mathern said. "We know when a medication has failed within months, yet I'm often seeing patients 4 or 5 years later. We have to get in there to stop the seizures and give the rest of the brain a chance to develop," he said.

"Two strikes and they're in for referral," Patrick Kwan, MD, task force chair, from the Chinese University of Hong Kong, told Medscape Neurology when the group's new definition was first unveiled. The goal, he pointed out, is to avoid unnecessary delays in altering the course of disease.

"Epilepsy is the Rodney Dangerfield of neurological diseases," Dr. Mathern added. "It gets no respect."

• Studies that are independent of the telecom industry consistently show there is a "significant" risk for brain tumors from cell phone use.
• The EMF exposure limits advocated by industry and used by governments are based on a false premise that a cell phone's electromagnetic radiation has no biological effects except for heating.
• The danger of brain tumors from cell phone use is highest in children, and the younger a child is when he/she starts using a cell phone, the higher the risk.

The issue of cell phone safety was to have been settled once and for all by the huge 13-nation industry-funded Interphone study, which was begun nearly 10 years ago. Even though data collection was completed in 2004, the results have still not been published. The European Parliament has called the delay "deplorable," and has demanded an explanation for it. Although the combined results have not yet been released, 14 Interphone studies (11 single country and 3 multicountry studies) with partial results have been published.

"Results of Interphone have been delayed by about 4 years," said Elizabeth Barris, founder of the nonprofit People's Initiative Foundation and coauthor of the new report, in an interview. "It was supposed to be released this September. We wanted to make sure that our report was released before Interphone. We wanted to bring attention to the issue, including the fact that Interphone has been delayed for so long."

With only 4 exceptions, the industry-funded Interphone studies found no increased risk for brain tumors from cell phone use, explained Mr. Morgan. In contrast, a series of Swedish studies, led by Lennart Hardell, MD, PhD, from the Department of Oncology, Orebro Medical Center, in Sweden, which were independent of industry funding, reported numerous findings of significantly increased brain tumor risk from cell phone and cordless phone use.

As you review these studies, you begin to get strong evidence of extremely improbable results.

An analysis of the results from the Interphone studies suggests that the use of a cell phone actually protects the user from a brain tumor, or that the studies had serious design flaws. "In any one study, you can see this incredibly skewing toward protection," said Mr. Morgan. "As you review these studies, you begin to get strong evidence of extremely improbable results."

In fact, Mr. Morgan and his coauthors identified 11 flaws in the Interphone studies: selection bias, insufficient latency time, definition of "regular" cell phone use, exclusion of young adults and children, no investigation of brain tumor risk from cell phones radiating higher power levels in rural areas, exclusion of exposure to other transmitting sources, exclusion of some brain tumor types, exclusion of tumors outside the cell phone radiation plume, exclusion of brain tumor cases because of death or illness, recall accuracy of cell phone use, and funding bias.

Initial Red Flags In the United States, the possible connection between tumors and cell phone use became highly publicized in 1993, when Florida resident David Reynard appeared on the popular television show Larry King Live and blamed cell phones for causing his wife's lethal brain tumor. Mr. Reynard filed a lawsuit against the manufacturer; he ultimately lost the case, but dozens of other lawsuits followed in its wake, along with numerous scientific studies that attempted to find or disprove a link. Most of the lawsuits have been dismissed, and thus far, none have gone to trial.

But the subject was picked up by the media, and scientists and experts argued publicly on opposing sides of the issue. Reports in the popular media prompted Congressional hearings on the safety of cell phone use, and during those sessions, it became clear that cell phones had not been tested for "safety prior to going into commerce," said George Carlo, PhD, MS, JD, during a 2008 radio interview with CFRO, a co-op radio station based in Vancouver, British Columbia. "Because the food and drug industry had not required that testing, Congress asked the industry to fill in those data gaps."

The industry invested $28.5 million and launched the first telecommunications industry-backed studies to investigate possible health risks stemming from cell phone use. Dr. Carlo, who is a Fellow of the American College of Epidemiology and has served on the faculty of several medical schools, headed the Wireless Technology Research program, which ran from 1993 to 1999. It was the largest program in the world to look at the potential dangers of cell phone use and electromagnetic radiation.

"In the middle of 1998, we began to have some of our long-term studies completed and it became clear that we were seeing things that no one expected," said Dr. Carlo. "We found that cell phone radiation caused leakage in the blood–brain barrier, it caused genetic damage in the form of disruption of normal DNA repair, and it caused more than a doubling of the risk of rare neuroepithelial tumors."

"After 6 years," he continued, "we found that cell radiation caused an increased risk of acoustic neuromas."

I don't think they ever really expected to find that cell phones were dangerous.

These were "red flags of risk"; there weren't enough data at the time to actually prove that the risk was real, Dr. Carlo emphasized. "That is not the case now; there has been confirmatory evidence. But in 1999, regulatory agencies did not have the scientific evidence to be able to sustain the types of legal challenges that would have come from the industry had they tried to ban cell phones."

Trail of Research

Much of the more recent research on the safety of cell phones has not specifically found a health risk; however, researchers have pointed out the limitations of their studies and left the door open. Part of the problem in assessing the potential connection between brain tumors and cell phone use is the relatively short period of time that the devices have been heavily in use in a large population and the long latency period for many tumors.

A National Cancer Institute study published in 2001, for example, did not support the hypothesis that the use of cell phones caused brain tumors, but the researchers noted that a limitation of their work was that they did not assess risks after a potential induction period of more than several years or among people with very high levels of daily or cumulative use (N Engl J Med. 2001;344:79-86).

A 2009 review from researchers at the Karolinska Institutet in Stockholm, Sweden, reported that studies published to date do not demonstrate an increased risk after approximately 10 years of use for any brain tumor or other head tumor (Epidemiology. 2009;20:639-652). Thus far, data do not suggest a causal association between cell phone use and fast-growing tumors, but they note that for slow-growing tumors, such as meningioma and acoustic neuroma, "the absence of association reported thus far is less conclusive because the observation period has been too short."

The Interphone studies to date have largely reported negative results, finding no association between tumors and cell phone use. One study did not find a link between an increased risk for malignant or benign parotid gland tumors and exposure to radiofrequency electromagnetic fields, but the authors concluded that cell phones "have not been used long enough to exclude their possible carcinogenic effect after long-term use, and more epidemiologic studies including long-term users are clearly warranted" (Am J Epidemiol. 2006;164:637-643).

However, the results of an Israeli Interphone study suggest a positive association between cell phone use and the development of parotid gland tumors (Am J Epidemiol. 2008;167:457-467). The authors noted that this was a single study, and therefore did not provide enough evidence to assume causality. They recommend additional investigations of this association, with longer latency periods and large numbers of heavy users, to confirm the findings. "Until more evidence becomes available, we believe that the precautionary approach currently adopted by most scientific committees and applied by many governments should continue to be used," they wrote.

Some of the strongest evidence supporting a link between brain tumors and cell phone use comes from a series of Swedish studies, led by Dr. Hardell. Overall, the reserachers found that risk increased with the number of cumulative hours of use, higher radiated power, and length of cell phone use. They also reported that younger users had a higher risk. In fact, the highest risk was among people who were younger than 20 years at the time of first use (Int J Oncol. 2006;28:509-518; Int Arch Occup Environ Health. 2006;79:630-639; Arch Environ Health. 2004;59:132-137; Pathophysiology. 2009;16:113-122).

A meta-analysis that incorporated 11 long-term epidemiologic studies in this field also reported a link between cell phone use and brain tumors. Using a cell phone for 10 years or longer was positively associated with the development of an ipsilateral brain tumor; in fact, it doubled the risk (Surg Neurol. 2009;72:205-214).

Melange of Reactions

As in the literature, there is no consensus among physicians and scientists about the severity of risk, or even if it exists. On its Web site , the National Cancer Institute notes that although a consistent link has not been demonstrated between cell phone use and cancer, "scientists feel that additional research is needed before firm conclusions can be drawn." Likewise, the American Cancer Society points out that although the weight of the evidence has shown no association between cell phone use and brain cancer, information on the potential health effects of very long-term use, or use in children, is not available.

Sam Milham, Jr. MD, MPH, former chronic disease epidemiologist at the Washington State Department of Health and clinical associate professor at the University of Washington School of Public Health in Seattle, has published several critiques on cell phones and health risks. "I personally think there is a real risk, and have felt this way even before the studies were published, based on animal work," he told Medscape Oncology.

Dr. Milham contends that all of the negative studies have been seriously flawed. "The fact that same-sided tumors with long latency are showing increased risks is bad news, since brain tumors have very long latencies," he said. "The same-sided risks are very important since dose is important. The most worrisome fact is the number of people who are being exposed."

Putting a cell phone against your head is like putting one side of your head against a microwave oven.

"Putting a cell phone against your head is like putting one side of your head against a microwave oven," he added.

Last year, Ronald B. Herberman, MD, director of the University of Pittsburgh Cancer Institute and UPMC Cancer Centers in Pennsylvania, sent a memo to faculty and staff advising them to limit cell phone use based on his interpretation of recent research. In 2008, he testified before a Congressional Subcommittee on the subject of tumors and cell phones, and urged more independent and definitive research.

However, many experts are not convinced that there is a link. Currently, there is no evidence that cell phones cause brain cancer, said John Moulder, PhD, professor and director of radiation biology at the Medical College of Wisconsin in Milwaukee.

The Road Ahead

On the heels of the release of the new cell phone report, a Senate hearing on the health effects of cell phone use was held in September, and chaired by Sen. Tom Harkin (D-Iowa). The take-away message from expert testimony was that more and better research is needed to determine if there is a risk to human health. And nearly all of the researchers and scientists who spoke at the hearing advocated a precautionary approach in the meantime.

We just don't know what the answer is.

"We just don't know what the answer is," said Sen. Arlen Specter (D-Pennsylvania) during the hearing. "Precautions are not a bad idea. They may not be a good idea, but they are not a bad idea. And the issue of children is something we should look at a little more closely."

Several countries, including Israel, France, and Finland, and the United Kingdom have decided not to wait for additional data; instead, they have issued warnings about the use of cell phones and advise taking precautionary measures, especially for children. New legislation in France, for example, will ban advertising of cell phones that is directed to children younger than 12 years of age and the sale of cell phones designed for children younger than 6 years. In addition, France will introduce new limits for radiation from the phones and require cell phones to be sold with earphones.

Realistically, it is going to be difficult to change behaviors now that cell phones are so entrenched in daily use, explained Mr. Morgan. "In some parts of the world, it is nearly impossible to get a land-line telephone, so cell phones are the only option."

Cell phones can be made safer, and the technology to do so exists right now. For example, said Mr. Morgan, "you can get a 10,000-fold reduction in exposure simply by keeping the phone 6 inches away from the head."

There are also steps that can be taken right now to make cell phones safer to use, he said. These include using a wired headset (not a wireless headset such as a Bluetooth), using speaker-phone mode, or sending text messages; keeping the phone away from the body when not in use; avoiding use in a moving car, train, or bus, or in rural areas at some distance from a cell tower, because any of these uses will increase the power of the cell phone's radiation; and keeping the cell phone turned off until you need to use it.

The authors also recommend using a corded land-line phone whenever possible, instead of a wireless phone, and to avoid cell phones when inside buildings, particularly with steel structures. Since children face a greater health risk, they should not be allowed to sleep with a cell phone under their pillows or at the bedside, said Mr. Morgan. Ideally, those younger than 18 years should not use a cell phone at all, except for emergencies.

June 16, 2009 — Surgery may be effective for pain relief in patients with degenerative spondylolisthesis with spinal stenosis, according to the results of a study reported in the June issue of the Journal of Bone & Joint Surgery (American Volume).

"The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial," write James N. Weinstein, DO, MS, from Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, and colleagues. "Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years. Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment."

At 13 centers, surgical candidates who had imaging showing degenerative spondylolisthesis with spinal stenosis and who had symptoms for at least 12 weeks were offered enrollment in a randomized cohort or observational cohort. Treatment options were usual nonsurgical management or standard decompressive laminectomy, with or without fusion. The main endpoints of the study were bodily pain and physical function scores on the Short Form-36 and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and annually up to 4 years.

Among the 304 patients enrolled in the randomized cohort, two thirds (66%) of those assigned to surgical management underwent surgery by 4 years, whereas approximately half (54%) of those assigned to nonsurgical management received surgery by 4 years. Among the 303 patients enrolled in the observational cohort, most (97%) of those who chose surgery received the surgery, whereas one third (33%) of those who chose nonsurgical management ultimately underwent surgery.

Based on intent-to-treat analysis of the randomized cohort, treatment outcomes between the operative and nonoperative groups were not significantly different at 3 or 4 years. However, nonadherence to the assigned treatment limited this analysis. The investigators therefore performed an as-treated analysis pooling the randomized and observational cohorts, with adjustment for potential confounders.

In the as-treated analysis, clinically important benefits of surgery that had been previously reported through 2 years were maintained at 4 years. Treatment effects were 15.3 for bodily pain (95% confidence interval [CI], 11 - 19.7), 18.9 for physical function (95% CI, 14.8 - 23), and –14.3 for the Oswestry Disability Index (95% CI, –17.5 to –11.1).

Benefits of surgical management seen at 2 years regarding secondary outcomes of bothersomeness of back and leg symptoms, overall satisfaction with current symptoms, and self-rated progress were also maintained at 4 years.

"Compared with patients who are treated nonoperatively, patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years," the study authors write.

Limitations of this study include nonadherence to assigned treatment and heterogeneity of the treatment interventions.

"In the as-treated analysis, combining the randomized and observational cohorts of patients with spinal stenosis secondary to degenerative spondylolisthesis, those treated surgically were found to have significantly greater improvement in scores for pain, function, satisfaction, and self-rated progress over four years compared with patients treated nonoperatively," the study authors conclude. "The results in both groups were stable between two and four years."

The best treatment of lumbar degenerative spondylolisthesis remains somewhat controversial, although the Spine Patient Outcomes Research Trial (SPORT) previously corroborated other research in that surgery appeared superior to conservative therapy in the short term. In a preliminary as-treated analysis by the authors of the current study, which was published in the May 31, 2007, issue of the New England Journal of Medicine, surgery was superior to conservative therapy by month 3 of the study, and this difference expanded at 1 year. Surgery was superior to nonoperative care in all of the major outcomes studied: pain, physical function, and disability; and there was only a slight decrease in the advantage of surgery vs conservative treatment 2 years after randomization.

Nonetheless, there has been concern regarding the long-term efficacy of surgery for lumbar degenerative spondylolisthesis vs nonoperative treatment. The current 4-year report from SPORT addresses this issue.

• Patients eligible for study participation had neurogenic claudication or radicular leg pain along with spinal stenosis and degenerative spondylolisthesis on imaging studies of the lumbar spine. All participants had symptoms present for at least 12 weeks and no evidence of spondylosis.
• The study cohorts consisted of a group of patients randomly assigned to operative or nonoperative care and an observational cohort who chose their own treatment.
• The protocol surgery consisted of a standard posterior decompressive laminectomy, with or without fusion. Nonoperative care consisted of physical therapy, analgesics, and epidural steroid injections.
• The main outcomes of the study were validated scales for body pain, physical function, and disability. These outcomes were measured annually after 2 years.
• The researchers analyzed operative and nonoperative care in both intent-to-treat and as-treated analyses, as there was significant crossover between assigned treatments.
• 304 individuals enrolled in the randomized group of SPORT, and 303 comprised the observational cohort.
• Among participants assigned to receive surgery in the randomized cohort, 64% had undergone surgery by 2 years, and this number increased to 66% at 4 years. Conversely, rates of surgery among participants randomly assigned to receive nonoperative care were 49% at 2 years and 54% at 4 years.
• There was less crossover of treatment among patients who made a choice of care in the observational cohort, but one third of participants who selected nonoperative care underwent surgery by year 4.
• Patients who underwent surgery were generally younger and experienced more symptoms and disability vs patients who received nonoperative care.
• On intent-to-treat analysis, operative and nonoperative care produced similar results for pain, function, and disability at 4 years.
• In contrast, as-treated analysis demonstrated superiority for surgery vs nonoperative care in all of these outcomes at 4 years. This analysis suggested that surgery was superior in both the randomized and observational cohorts.
• Patients with neurogenic claudication at baseline particularly benefited from surgical treatment vs nonoperative care. However, the presence of a neurologic deficit on examination did not affect study outcomes.
• Complications were rare among patients receiving operative or nonoperative treatment. After surgery, the 4-year reoperation rate was 15%, and the rate of recurrent stenosis was 5%. The mortality rate was lower for both treatment groups vs actuarial projections.

• In a previous as-treated analysis from SPORT, surgery was superior to conservative therapy among patients with lumbar degenerative spondylolisthesis at 3 months through 2 years of follow-up. Surgery alleviated pain, improved physical function, and reduced disability vs conservative therapy.
• The current analysis of SPORT suggests that surgery continues to produce superior outcomes vs nonoperative care at 4 years among patients with a history of lumbar degenerative spondylolisthesis.