Research news and notes

1. Overview of outcomes of surgical and endovascular treatment of aneurysms 

Many publications addressed the outcomes of surgical and endovascular treatment of aneurysms. In a recent issue of Lancet Neurology, Qureshi et al [2] summarized data from a large variety of studies, including randomized clinical trials as well as single and multicenter studies. The articles were mostly from the past decade. Surgical treatments in the analysis included direct clipping, trapping with or without bypass, wrapping, and clipping of aneurysm after incomplete coiling. Endovascular treatments included coiling with or without stents and balloon assistance, as well as liquid embolic agent. They also included coiling of remnant of aneurysm after surgical clip placement. In summary, the rate of initial obliteration of aneurysm was greater after surgical clipping, but the recovery was faster after endovascular treatment. The outcomes at 6 months, 1 year, and even later in those studies that had longer follow-up were all better for endovascular treatment. Follow-up for more than 5 years was not generally available. According to the authors, despite the lower initial obliteration rate and the need for retreatment, endovascular treatment still demonstrated superior outcomes. Endovascular treatment is still evolving, and a greater number of patients with aneurysms are becoming candidates for this treatment. This summary of literature helps all of us who refer patients to endovascular therapy feel better about it. The current evidence appears to suggest that, if the aneurysm has the shape and location that are amenable to endovascular treatment, it is at least a valid alternative, and even if the aneurysm is not completely obliterated, the outcome remains good. Actually, this conclusion makes empirical sense—avoiding craniotomy and its risks must improve short-term and even medium-term outcomes.

Has the new era arrived? Is the current endovascular treatment indeed better than open surgical clipping? I am not sure yet. Let us play the devil's advocate. Suppose that surgery reliably prevents rebleeding but carries a 10% risk of serious morbidity and mortality. Let us also suppose that aneurysms treated with coils have the same long-term risk of rupture as untreated aneurysms—let us say 0.5% per year. In this situation, the overall outcome in the endovascular group would be much better in the first several years after the treatment, even if the endovascular treatment were no better than placebo! A recent study of 393 consecutive patients in the Netherlands [3] revealed a rebleeding rate of 0.32% per year in patients with coiled aneurysms. During the follow-up (median of 4 years) 13% of the aneurysms were additionally treated with more coiling or clipping. It is safe to assume that such retreatment prevented more cases of rebleeding. Nobody knows what will happen after routine follow-up angiograms stop and patients are no longer retreated. There is no current recommendation for indefinite angiographic follow-up, nor an estimate of the lifetime risk of routine cerebral angiograms. It is reasonable to suppose that given long-enough follow-up, better aneurysm obliteration rate after surgical clipping can offset the initial additional risk of surgery. Only truly long follow-up of a large number of patients can directly demonstrate the real and clinically relevant difference in outcome between the endovascular and the open surgical groups. The risk of rebleeding does not arbitrarily stop after 5 years or any other predetermined number of years but must be extrapolated for the rest of the patient's life expectancy. Any comparison of outcomes that is based on an artificial target date is biased.

2. Chocolate treats elevated blood pressure 

I guess that no food is associated with almost addictive craving as much as chocolate. It is usually packed with calories in the form of sugar and saturated fat and, thus, is typically perceived as a “sinful” and unhealthy food. Maybe this perception should change, especially for “real” chocolate—the dark variety. A recent randomized trial from Germany [4] demonstrated reduction in blood pressure with even small doses of dark chocolate. The study involved 44 volunteers, men and women 55 to 75 years old, who had prehypertension or stage I hypertension (blood pressure 130/85 to 160/100 mm Hg). The subjects were sent in an investigator-blinded fashion either 6.3 g of dark chocolate or 5.6 g white chocolate. The weights were different to get the same caloric intake—30 kcal per piece. They were instructed not to eat any product with cocoa and kept a food diary. Blood pressure readings were performed under standardized conditions by trained personnel who were blinded to the patient group assignment. The patient groups were similar in terms of age, weight, serum lipids, and other parameters. Their diets were also similar. At the end of 18 weeks of experiment, patients who received dark chocolate had a significant decrease in systolic blood pressure by 2.9 mm Hg and diastolic by 1.9 mm Hg. The decrease was greater in those patients who had a higher blood pressure at the start of the experiment. The authors refer to prior studies that demonstrated a beneficial effect on endothelial function of large doses of cocoa or habitual use of cocoa. This study shows a measurable benefit and blood pressure reduction from only 1 piece of dark chocolate a day. The benefit of chocolate is ascribed to cocoa polyphenols that increase the production of nitric oxide in vascular endothelium. The decrease in blood pressure is small but not negligible because even a small reduction in blood pressure can affect mortality. I liked this article not only because it was rigorously designed and conducted but also because this type of research is difficult to fund and conduct. There is no new medication or procedure involved—in the United States, it may not have been possible to attract either government or corporate sponsorship. The study was sponsored by the University Hospital of Cologne, and I would like to congratulate both the authors and the sponsors.

3. Surgery is better than prolonged conservative treatment for sciatica 

The recent publication of the Spine Patient Outcomes Research Trial (SPORT) study has focused renewed attention on the indications for surgery in patients with radiculopathy without progressive neurological deficit. In the May 31 issue of the New England Journal of Medicine, Peul et al [1] present a different study that compared surgery and prolonged “conservative” management for severe sciatica. To minimize crossover rates, the study specified early surgery—within 2 weeks of assignment, for the surgical group. The authors randomly assigned 283 patients who had had severe sciatica and herniated disc for 6 to 12 weeks to either early surgery or prolonged nonoperative management, and followed them up for a year after randomization. Most (89%) of patients assigned to surgery had a microdissectomy after a mean of 2.2 weeks. A large minority (39%) of patients assigned to “conservative” treatment were treated surgically after a mean of 18.7 weeks. At 1-year follow-up, most patients (95%) overall had perceived recovery regardless of treatment assignment, but the surgical group demonstrated faster relief of pain and subjective recovery. There was no difference in disability between the groups. Interestingly, surgery tended to benefit more those patients who had provocation of sciatica by sitting. The study was analyzed by intent to treat only—the benefit of surgery in patients who were randomized to nonoperative management but were operated was assigned to the conservative treatment. The authors concluded that the 1-year outcomes were the same in patients assigned to early surgery and those assigned to conservative treatment first, but the rate of pain relief and perceived recovery were faster with surgery. Thus, the benefit of early surgery was so robust that it persisted even despite a 39% crossover. It is possible that strict adherence to nonoperative regimens could have resulted in a worse long-term outcome for any group of patients for whom surgery is not available at all. My conclusion from this article—patients with sciatica who already waited 6 to 12 weeks with nonoperative management do better with early surgery. The term conservative is a misnomer commonly applied to nonoperative treatment. In some cases, the traditional, safe, and sound “conservative” approach is surgical, and the medical approach is more radical and extreme. For example, medical treatment of appendicitis with fluids and antibiotics is more radical than an appendectomy. I propose that early surgery in patients with persistent sciatica is the more conservative treatment, and extended medical treatment despite severe pain is more radical.

4. Even mild anemia may increase perioperative risk 

How safe is it to operate on elderly patients with mild anemia? In the June 13 issue of JAMA, Wu et al [5] present a very extensive study using the Veterans Administration National Surgical Quality Improvement Program Database. They estimated the changes in 30 postoperative outcomes and cardiac events in relation to each hematocrit point deviation from the reference range (39%-53.9%). There were 310311 veterans 65 years and older in this retrospective cohort. All had major noncardiac surgery in 1997 to 2004. Every point deviation from the norm was associated with a 1.6% increase in mortality. Further analysis demonstrated that hematocrit above 51%, although a priori in the reference range, was associated with increased mortality. Morbidity and cardiac events also increased. Although none of the 20 most common procedures tracked by the program is neurosurgical, the results can probably be extrapolated to neurosurgical patients. What we do not know is whether treatment of anemia before surgery will improve the outcome. Possibly, the extra risk comes from the same disease that caused the anemia, rather than the hematocrit value itself. Further research into the outcome of intervention and anemia correction is needed but will be difficult—huge numbers of patients may be needed to see a benefit of intervention.