Comment
Surgery versus conservative treatment for intracerebral
haemorrhage—is there an end to the long controversy?
The International STICH trial, reported by David Mendelow
and colleagues in today’s Lancet, is a long-awaited study.
The results of STICH have already attracted the attention of
physicians engaged in stroke medicine. Is surgery for spontaneous intracerebral haemorrhage beneficial compared
with conservative treatment? Since the trial by McKissock et
al, in 1961,1 seven randomised trials have been reported,2–7
and there have been three meta-analyses of these trials.8–10
Yet conclusions of whether surgery is beneficial over conservative treatment remain controversial. The reason is that
these studies had only weak analytical power because they
were small and limited to local areas. STICH is the first large
multicentre randomised trial, and recruited 1033 patients
from 83 centres in 27 countries.
Mendelow and colleagues included some new features in
STICH. The first was adoption of prognosis-based outcome
for evaluation of patients’ outcome. This method first
divides patients into groups by good and poor prognosis
based on their clinical status at randomisation, and assesses
outcomes of these groups by a different outcome threshold. Prognosis for patients with spontaneous intracerebral
haemorrhage is correlated with age and the volume and
location of haematomas before treatment. If groups of
patients with differences in clinical condition are assessed
on the basis of the same criteria, the interpretation of
results will lack precision. Adoption of prognosis-based outcome solves this problem and makes results of the STICH
study pragmatic.
Second, the surgery group was limited to patients who
had early surgery, on the basis that many neurosurgeons
believe early clot-removal is effective in rescuing the
penumbra surrounding the haematoma, and on experimental study.11 However, as in conventional trials, there
was no evidence of overall benefit with a policy of early
surgery compared with initial conservative treatment in
STICH. We do not believe, however, that this result directly
challenges the usefulness of surgery for spontaneous
intracerebral haemorrhage. We consider it important that
of the patients randomised to initial conservative treatment, 26% needed surgery a few days after randomisation.
Because the most common reason they required surgery
was neurological or clinical deterioration and they were
more likely to have haematomas with a volume greater
than 50 mL, subsequent brain oedema must have increased
compression of the surrounding normal tissues in those
patients. These crossovers should be regarded as candidates
for surgery, although they were randomised to initial conservative treatment. Surgery in the early stage might have
prevented subsequent brain oedema associated with neurological deterioration in these patients.
Besides appropriate selection of subgroups of patients for
surgery, it is important to improve operative techniques to
obtain good surgical results. The results of STICH show that
there is more likely to be a favourable outcome of surgery,
mainly craniotomy, if the haematoma is 1 cm or less from
the cortical surface, and significant interaction was shown
between depth from the cortical surface and efficacy of
treatment. The reason is that if the haematoma is near the
cortical surface, surgical destruction of brain tissue in reaching the haematoma is minimal. For deep haematomas,
such as those in the basal ganglia or thalamus, benefits like
those of craniotomy for subcortical haematoma will be
obtained if a less invasive, safe, and effective method of clot
evacuation exists. Endoscopic surgery is one of the
methods expected to be effective for treatment of deep
haematoma.7–9 From a similar point of view, we have developed endoscopy for surgery for intracerebral haemorrhage,
have treated patients with it, and now are making an effort
to improve it (figure).12 We expect that such technical
progress will open new possibilities for treatment of intracerebral haemorrhage, and, in the future, yield results different from that of International STICH.
See Articles page 387
*Takahiro Nakano, Hiroki Ohkuma
Department of Neurosurgery, Hirosaki University School of
Medicine, Zaifucho 5, Hirosaki, 036–8562 Japan
[email protected]
We declare that we have no conflict of interest.
1
Figure: Endoscopic system specialised for intracerebral haemorrhage surgery
New steerable endoscope for intracerebral haemorrhage surgery to obtain
manoeuvrability needed for effective evacuation of clot.
www.thelancet.com Vol 365 January 29, 2005
2
McKissock W, Richardson A, Taylor J. Primary intracerebral haemorrhage:
a controlled trial of surgical and conservative treatment in 180 unselected
cases. Lancet 1961; 2: 221–26.
Auer LM, Deinsberger W, Niederkorn K, et al. Endoscopic surgery versus
medical treatment for spontaneous intracerebral hematoma: a randomized
study. J Neurosurg 1989; 70: 530–35.
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Comment
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4
5
6
7
8
Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous
intracerebral hemorrhage. J Neurosurg 1989; 70: 755–58.
Batjer HH, Reisch JS, Allen BC, et al. Failure of surgery to improve
outcome in hypertensive putaminal hemorrhage. Arch Neurol 1990; 47:
1103–06.
Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for
intracerebral hemorrhage (STICH). Neurology 1998; 51: 1359–63.
Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for
supratentorial intracerebral hemorrhage: a randomized feasibility study.
Stroke 1999; 30: 1833–39.
Tan SH, Ng PY, Yeo TT, et al. Hypertensive basal ganglia hemorrhage:
a prospective study comparing surgical and nonsurgical management.
Surg Neurol 2001; 56: 287–93.
Hankey GJ, Hon C. Surgery for primary intracerebral hemorrhage: is it safe
9
10
11
12
and effective? A systemic review of case series and randomized trials.
Stroke 1997; 28: 2126–32.
Prasad K, Browman G, Srivastava A, et al. Surgery in primary supratentorial
intracerebral hematoma: a meta-analysis of randomized trials.
Acta Neurol Scand 1997; 95: 103–10.
Fernandes HM, Gregson B, Siddique S, Mendelow AD. Surgery in
intracerebral hemorrhage: the uncertainty continues. Stroke 2000; 31:
2511–16.
Wagner KR, Xi G, Hua Y, et al. Clot removal following lysis with tissue
plasminogen activator markedly reduces perihematomal edema in an
intracerebral hemorrhage model. Stroke 1996; 27: 183.
Nakano T, Ohkuma H, Ebina K, Suzuki S. Neuroendoscopic surgery for
intracerebral haemorrhage: comparison with traditional therapies.
Minim Invas Neurosurg 2003; 46: 278–83.
Smallpox vaccines: from first to second to third generation
See Articles page 398
In this issue of The Lancet, Richard Greenberg and colleagues
report a trial that compared a new smallpox vaccine derived
from cell culture with a vaccine derived from calf lymph.
Their report is timely, given current concerns over biological
weapons.
The smallpox vaccines currently licensed in the USA and
UK are live, attenuated vaccinia virus derived from calf
lymph. Although this type of vaccine was used to eradicate smallpox worldwide, well-documented safety limitations prevent its widespread use in a civilian population
without an outbreak. Historically, out of every million
people vaccinated for smallpox, 14–52 people had serious
or life-threatening adverse reactions to the vaccine, and one
Wellcome Library, London
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Jenner inoculating patients against smallpox
362
to two people per million primary vaccinees died because of
the vaccine.1 Serious side-effects include eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, fetal
vaccinia, vaccinia keratitis, and myopericarditis. There were
also cases of inadvertent self-inoculation and vaccinated
people transmitting vaccinia vaccine virus to others.2 Also,
smallpox vaccine is contraindicated in up to 30% or more of
the population, including infants, pregnant women or
women who are breastfeeding infants, the immunocompromised, those with eczema or exfoliative skin disorders, people who live in the same house or are in intimate
contact with people with the above conditions, and people
with cardiovascular conditions (such as a history of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischaemic attack, chest pain or
shortness of breath with activity, or any cardiac condition
under the care of a physician).3,4
In their trial, Greenberg and colleagues randomly
allocated 350 healthy adults to receive cell-cultured
smallpox vaccine (CCSV) or calf-lymph-derived vaccine
(Dryvax). Participants included 150 vaccinia-naive people
18–30 years of age, and 100 participants who were not
naive to vaccinia and 32–65 years of age. A further
100 vaccinia-naive people 18–30 years of age received one
of five CCSV doses of various dilutions in a single-blind
manner. To assess safety and immunogenicity, researchers
made physical examinations, recorded adverse events and
take-rates, and performed neutralisation antibody titres,
T-cell proliferative-response assays, and interferon-
Elispot. The last two assays were designed to measure cellmediated immunity.
All but one participant developed pock lesions. Vaccineassociated adverse reactions were similar between the CCSV
and Dryvax recipients. Although none of the participants
had serious vaccine-related adverse events, the vaccinenaive recipients had the expected side-effects: erythema,
axillary adenopathy, swelling, pain, and lymphangitis. The
number of participants who became immune to the virus
was high, although antibody seroconversion rates were
lower in CCSV recipients, while measures of cell-mediated
www.thelancet.com Vol 365 January 29, 2005