Fakty i Mity Nr44 08.11.2012, FAKTY i MITY [PDF]
Fakty i Mity Nr.41 18.10.2012, FAKTY i MITY [PDF]
Fakty i Mity Nr.43 01.11.2012, FAKTY i MITY [PDF]
Fakty i Mity Nr.40 11.10.2012, FAKTY i MITY [PDF]
Fire.With.Fire.2012.HD 720p.BRrip.x264. Napisy PL, @@@ FILMY HD. Wielka Rozdzielczość, Mała Waga. SPRAWDŹ TO !!!
Full Track List, - ◢ M ◤ Sandra Cretu Collection ▬▬▬▬▬◥◤▬▬▬▬▬, Sandra - Discography Lighting & Studio Albums (1985-2012)
Frommers Cancun & Yucatan 2012, Travel Guides- Przewodniki (thanx angielski i stuff)
Frommer s France 2012, Travel Guides- Przewodniki (thanx angielski i stuff)
Frommers Italy 2012, Travel Guides- Przewodniki (thanx angielski i stuff)
Frommers Bermuda 2012, Travel Guides- Przewodniki (thanx angielski i stuff)
Fluorescence Tykocki, Neurologia i Neurochirurgia Polska od 2012
[ Pobierz całość w formacie PDF ]SHORT REPORT/KRÓTKIE DONIESIENIE
Fluorescence-guided resection of primary and recurrent malignant gliomas
with 5-aminolevulinic acid. Preliminary results
Wyciêcie pierwotnych z³oœliwych glejaków mózgu oraz ich wznów pod kontrol¹
fluorescencji zzastosowaniem kwasu 5-aminolewulinowego. Wyniki wstêpne
Tomasz Tykocki
1
, Rados³aw Michalik
2
, Wies³aw Bonicki
2
, Pawe³ Nauman
1
1
Department of Neurosurgery, Institute of Psychiatry and Neurology in Warsaw
2
Department of Neurosurgery, Maria Sk³odowska-Curie Memorial Cancer Centre, Institute of Oncology, Warsaw
Neurologia i Neurochirurgia Polska 2012; 46, 1: 47-51
DOI: 10.5114/ninp.2012.27212
Sttreszczeniie
Absttractt
Backgrround and purrposse:: Extent of resection plays akey role
in the treatment of malignant gliomas (MGs). Patients with
complete glioma removal, followed by chemoradiation, obtain
the longest overall and progression-free survival. Fluores-
cence-guided resection of MGs enables intraoperative
visualization of glioma tissue and increases control of
the resection. The authors present preliminary results of
5-aminolevulinic acid (5-ALA) application during the resec-
tion of primary and recurrent MGs.
Matterriiall and metthodss:: Six patients with either a suspected
malignant glioma based on magnetic resonance imaging
(MRI) or with recurrent glioblastoma multiforme were
enrolled in the study. The extent of resection was calculated
according to the postoperative MRI performed within 72 hours.
Preoperative and early postoperative neurological status and
Karnofsky Performance Scale (KPS) were compared.
Ressullttss:: Fluorescence of tumour tissue was observed in
5/6 patients (five with the histopathological diagnosis of
glioblastoma multiforme and one with neurotoxoplasmosis and
AIDS). Complete tumour resection was achieved in 5 patients.
Postoperative KPS and neurological status deteriorated in
2 cases. Radiotherapy and chemotherapy did not interfere with
the sensitivity of the fluorescence guided tumour visualization.
Wssttêp ii cell prracy:: Zakres wyciêcia guza odgrywa kluczow¹
rolê w leczeniu z³oœliwych glejaków mózgu. Chorzy, u któ-
rych wykonano ca³kowite wyciêcie z³oœliwego glejaka mózgu
i których poddano nastêpnie radioterapii i chemioterapii,
uzyskuj¹ zarówno najd³u¿szy ca³kowity czas prze¿ycia, jak
i najd³u¿szy okres bez progresji choroby. Wyciêcie z³oœliwe-
go glejaka mózgu ukierunkowane fluorescencj¹ umo¿liwia
œródoperacyjne uwidocznienie tkanki glejaka oraz poprawia
kontrolê wczasie operacji. Autorzy prezentuj¹ wstêpne wyni-
ki zastosowania kwasu 5-aminolewulinowego (5-ALA) pod-
czas usuwania pierwotnych z³oœliwych glejaków mózgu oraz
ich wznów.
Matterriia³³ iimettody:: Do badania zosta³o w³¹czonych 6 chorych,
uktórych na podstawie badania za pomoc¹ rezonansu magne-
tycznego (RM) podejrzewano z³oœliwego glejaka mózgu albo
odrost glejaka wielopostaciowego. Zakres wyciê cia oceniano
na podstawie RM wykonanego wci¹gu 72 godz. po operacji.
Stan neurologiczny chorych oraz ocenê wskali Karnofsky’ego
(KPS) porównywano przed operacj¹ i we wczesnym okresie
po operacji.
Wyniikii:: Fluorescencja tkanki guza by³a widoczna u5 z 6 pa -
cjentów (u 5 rozpoznano histopatologicznie glejaka wielopo-
staciowego, ujednego chorego – neurotoksoplazmozê wprze-
Correspondence address: Tomasz Tykocki, Department of Neurosurgery, Institute of Psychiatry and Neurology in Warsaw, Sobieskiego 9, 02-957 Warszawa,
Poland, e-mail: ttomasz@mp.pl
Received: 19.03.2011; accepted: 25.11.2011
47
Neurollogiia ii Neurochiirurgiia Pollska
2012; 46, 1
Tomasz Tykocki, Rados³aw Michalik, Wies³aw Bonicki, Pawe³ Nauman
Concllussiionss::
Fluorescence-guided resection of primary and
recurrent MGs with 5-ALA improves control of the tumour
resection. It enables the cytoreduction to be maximized but
experience in neuro-oncological surgery is required to avoid
serious, postoperative neurological deficits.
Key worrdss:: malignant gliomas, fluorescence, resection.
biegu AIDS). Makroskopowo ca³kowite wyciêcie guza uzy-
skano u 5 chorych. Pooperacyjnie pogorszenie stanu neuro-
logicznego oraz wskali KPS stwierdzono u2 chorych. Radio-
terapia ani chemioterapia nie wp³ywa³y na wystêpowanie
fluorescencji podczas wyciêcia guzów.
Wniiosskii::
Wyciêcie pierwotnych z³oœliwych glejaków mózgu
oraz ich wznów ukierunkowane fluorescencj¹ z zastosowa-
niem 5-ALA poprawia kontrolê œródoperacyjn¹ podczas usu-
wania guza. Umo¿liwia osi¹gniêcie maksymalnej cytoreduk-
cji, jednak aby unikn¹æ powa¿nych deficytów neurologicznych
wokresie pooperacyjnym, potrzebne jest doœwiadczenie wchi-
rurgii neuroonkologicznej.
S³³owa klluczowe:: glejaki z³oœliwe, fluorescencja, usuniêcie
guza.
mary MG resections with 5-ALA, confirmed the prog-
nostic preliminary results [4]. Early postoperative con-
trol MRI revealed that total tumour resection, defined as
no contrast enhancement, was achieved in 90 (65%) of
139 patients in the fluorescence group compared with
47 (36%) of 131 in the white light group. Six-month PFS
was twice as long in the 5-ALA resected group compared
with the white light group. Five-ALA was also effective-
ly used for resection of recurrent MGs [6].
The authors present preliminary results of fluores-
cence-guided resection of primary and recurrent gliomas
with 5-ALA. Special attention is paid to intraoperative
techniques in MG resections.
IInttroducttiion
Malignant gliomas (MGs) are extremely invasive
brain tumours with a high proliferative rate. In spite of
significant progress in operative techniques and advances
in radiotherapy and chemotherapy, the median survival
time is still estimated at less than 2 years after the diag-
nosis of glioblastoma multiforme [1]. Recent studies
advocate cytoreduction as the first line treatment for
MGs [2-4]. However, there is still astrong conviction
that due to the diffuse tumour nature, cytoreduction is
ineffective and tumour biopsy with histopathological
diagnosis following oncological treatment should be an
initial therapeutic option. Considering the variety of cli -
nical approaches, neurosurgical resection of MGs pro-
vides rapid reduction of tumour mass and prolongs pro-
gression-free survival (PFS) and overall survival (OS).
Therefore, intensive research is being done to optimize
the intraoperative visualization and evaluation of real
time control of the surgical resection.
The last decades have resulted in the introduction of
modern intraoperative techniques: intraoperative mag-
netic resonance imaging (MRI), neuronavigation, ultra-
sonography and photodynamic technique. Fluorescence-
guided resection is performed with preoperative oral
administration of 5-aminolevulinic acid hydrochloride
(5-ALA). Five-ALA is a pro-drug that is metabolised
intracellularly in enzymatic reactions to protoporphyrin IX
(PPIX). The exogenous application of 5-ALA results in
its accumulation and transformation mainly to PPIX, but
not selectively in malignant glioma tissue. The concen-
tration of PPIX is significantly lower in normal brain
tissue than in MGs [5]. A randomized multicenter
phase III study, which evaluated fluorescence-guided pri-
Matteriiall and metthods
Six patients, with either a suspected MG based on
MRI scans or with recurrent glioblastoma multiforme
with histopathological diagnosis, were enrolled in the
study. The following clinical data were determined for
each patient: age at the time of operation, gender,
tumour location, preoperative and postoperative Karnof-
sky performance scale (KPS), and neurological status
(Table 1). Endpoints used in this study were extent of
resection and early postoperative neurological status.
Postoperative MRIs were performed within 72 hours
after surgery. The extent of resection was calculated
using MIPV (Medical Image Processing, Analysis and
Visualization) software, version 5.1.1. Images were
acquired from a1.5T MR scanner using aT1-weight-
ed imaging protocol with avoxel size of 4mm × 6mm
× 6 mm (0.14 mL). The criterion for the residual
tumour was the contrast enhancement volume greater
than 0.28 mL (double voxel volume).
48
Neurollogiia ii Neurochiirurgiia Pollska 2012; 46, 1
Fluorescence-guided resection of malignant gliomas with 5-ALA
Tablle 1..
Preoperative characteristics of patients
Pattiientts
Gender
Age
Tumour
Karnoffsky perfformance
Neurollogiicall
Radiiottherapy/
llocalliizattiion
scalle score
deffiiciitts
chemottherapy
Patient 1
male
70
right temporal lobe
70
none
yes
Patient 2
female
33
left frontal lobe
60
none
yes
Patient 3
male
44
left fronto-parietal area
70
none
no
Patient 4
female
60
right parietal lobe
60
left upper limb paresis
yes
Patient 5
male
58
right parietal lobe
70
psychomotor retardation
no
Patient 6
male
42
left frontal lobe
80
none
no
Tablle 2..
Postoperative characteristics of patients
Pattiientts
Karnoffsky perfformance
Neurollogiicall deffiiciitts
Hiisttopatthollogiicall
Resecttiion
Flluorescence
scalle score
diiagnosiis
Patient 1
70
none
recurrent GM
total
positive
Patient 2
60
none
recurrent GM
total
positive
Patient 3
70
none
GM
total
negative
Patient 4
50
left hemiparesis
recurrent GM
total
positive
Patient 5
60
psychomotor retardation
neurotoxoplasmosis/AIDS
total
positive
Patient 6
90
none
GM
partial
positive
GM – glioblastoma multiforme
Pre-treatment with dexamethasone (4mg three times
daily) was obligatory for at least 2 days before surgery
and until an early MRI scan had been obtained (with-
in 72 hours after surgery). Patients received freshly pre-
pared 5-ALA solutions (20 mg/kg body weight) orally
3 hours before the induction of anaesthesia.
The study required the tumour resections to be as
complete as possible with the priority of avoiding serious
neurological complications. In all patients the tumour
was resected using an NC 4 OPMI Pentero Neuro FL
surgical microscope (Zeiss, Oberkochen, Germany),
which enabled switching from conventional standard
xenon light to filtered, violet blue excitation light for visu-
alizing fluorescence. Additionally, the BrainLab naviga-
tion system was employed for planning the approach and
during tumour removal. All patients were evaluated neu-
rologically within 24 hours after the operation.
All participants in the study gave informed, written
consent for the surgery with 5-ALA and were informed
about possible complications.
MG was suspected due to the MRI findings. Patients
from the recurrent glioma group received preoperative
radiochemotherapy or radiotherapy alone. Intraopera-
tive fluorescence with blue light was visible in 5 cases.
There was no 5-ALA visualization in one case with sub-
sequent histopathological diagnosis of glioblastoma mul-
tiforme. There was one case with postoperative diagno-
sis of cerebral toxoplasmosis and AIDS, in which the
intensity of fluorescence was comparable to that observed
in MGs. Radiotherapy alone or radio chemo therapy did
not reduce the quality of 5-ALA visualization.
Complete tumour resection, defined as no contrast
enhancement on postoperative MRI, was achieved in
5/6 patients, including those with neuroinfection and
with no intraoperative fluorescence. In a case with par-
tial resection, the marginal portion of the primary glioma
could not be removed due to infiltration of the left insu-
la. The neurological status and KPS of two patients dete-
riorated due to the progression of paresis and psy-
chomotor retardation (Table 2).
Resulltts
Technical note
All the operations were performed with the support
of neuronavigation. During preoperative planning, two
Three of 6 patients enrolled in the study had re cur -
rent glioblastoma multiforme and in three other pa tients
49
Neurollogiia ii Neurochiirurgiia Pollska
2012; 46, 1
Tomasz Tykocki, Rados³aw Michalik, Wies³aw Bonicki, Pawe³ Nauman
objects were created, one corresponding to contrast
enhancement on T1-weighted MRI, the second related
to hyperintensity on FLAIR MRI. Both objects were
injected into the microscope view intraoperatively. Cra-
nial approaches were planned on the basis of FLAIR
MRI in three planes. To avoid significant ‘brain shift’
after dura and arachnoid opening, the authors paid spe-
cial attention to the proper fixation and positioning of
the head. Additionally, to reduce navigation error, the
localization of the tumour took place as soon as possi-
ble after dura opening. Blue light was initialized after
the tumour localization to verify the extent of fluores-
cence. At later stages of the procedure, blue light was
repeatedly applied according to the decision of the neu-
rosurgeon. The resection itself was performed with white
light and blue light was switched on for a few seconds
only to navigate and verify the border of the tumour.
The microscopic view with blue light was not of suffi-
cient quality to safely perform the procedure. Optimal
fluorescence was obtained when the operating field was
cleaned of haemorrhages. At each stage of the resection,
aneurosurgeon should be aware of the location of func-
tional areas, because the territory of fluorescence may
be more extensive than was expected before the opera-
tion. In addition, the fluorescence may encourage one
to expand the resection. Fluorescence-guided resection
may require decision-making during the operation relat-
ed to counterbalancing the range of resection and the
risk of neurological complications, so the patient should
be informed about this issue before the operation. It is
worth remembering that the fluorescence intensity
decreases around 30 minutes after the initiation of
blue light, but the authors did not observe this effect.
The fluorescence-guided technique does not lengthen
the time of the operation, since switching on and off the
blue light only requires pressing the programmed but-
ton on the handle of the microscope.
less, the most significant conclusion from the EORTC
study was that OS after either radiochemotherapy or
radiotherapy alone was greatest in patients assessed to
have had complete resections, compared with those with
incomplete resections or biopsies.
Lacroix
et al.
[2] estimated that the extent of resec-
tion greater than 98% causes a significant increase in
OS. Stummer
et al.
[4] presented the results of a ran-
domized multicentre phase III trial of surgical treatment
of MGs with the use of 5-ALA. The results showed that
fluorescence-guided resection allowed for complete
tumour removal in 65% of cases. This percentage is
almost twice that obtained with standard resection.
In this study the authors present early, postoperative
results of MG resections with 5-ALA. In 5/6 patients
with primary or recurrent glioma, intraoperative fluo-
rescence enhancement was observed. In one case, where
the GM was suspected both on MRI and intraopera-
tively, histopathological diagnosis confirmed
Toxoplasma
cysts in patient with HIV infection. It is noteworthy that
the intensity of fluorescence in infected tissue was com-
parable to that seen in GM. The explanation of this
effect could be the capability of
Toxoplasma gondii
to
biosynthesize tetrapyrrole from two 5-ALA molecules
using porphobilinogen synthase and finally to produce
PPIX [8]. Cerebral HIV infection may lead to neu-
rovasculitis with subsequent damage of the blood-brain
barrier (BBB) mainly due to the overexpression of adhe-
sion molecules and increased endothelial permeability
[9]. Disrupted BBB enables crossing and accumula-
tion of 5-ALA in the infected brain tissue.
The fluorescence-navigated resection with 5-ALA
entails ahigh risk of postoperative neurological deficits,
and therefore the support of neuronavigation and intra-
operative MRI is recommended. A particularly high
risk of morbidity in the early postoperative period was
observed among patients who did not respond to pre-
operative steroid treatment [10].
Diiscussiion
Concllusiions
MGs belong to ahistologically heterogeneous group
of brain tumours. The aims of the therapy are prolon-
gation of PFS and OS and improvement of the quality
of life. Cytoreduction with subsequent radiochemother-
apy is recommended as the best medical treatment [7].
In 2005, the results of the EORTC-26981 study were
published [1]. According to EORTC, patients showed
promising outcomes of chemoradiation, which was rec-
ommended as a standard treatment of GM. Neverthe-
1. Fluorescence-guided resection of MGs is an excel-
lent technique for intraoperative detection and dif-
ferentiation of tumour tissue from normal brain,
increasing intraoperative resectional control, decision-
making and comfort for the neurosurgeon.
2. Operations with 5-ALA should be performed by
experienced neurosurgeons, while fluorescence navi -
gated, expansive tumour removal entails a high risk
50
Neurollogiia ii Neurochiirurgiia Pollska 2012; 46, 1
Fluorescence-guided resection of malignant gliomas with 5-ALA
of severe postoperative neurological deficits. The
authors recommend using a neuronavigation system
as an assistant tool. The importance of intraoperative
MRI is raised in the literature [11], but the authors
have no experience on this field.
3. Preoperative planning of the neurosurgical approach
should consider alarger volume of glioma when visu-
alized with fluorescence than the contrast enhance-
ment of the tumour mass observed on MRI.
4. MG resection with 5-ALA increases the percentage
of cases with complete glioma resection, which is the
predictive value for prolongation of PFS and OS.
glioma surgery: a supplemental analysis from the randomized
5-aminolevulinic acid glioma resection study.
J Neurosurg
2010;
114: 613-623.
11. Senft C., Bink A., Heckelmann M., et al. Glioma extent of
resection and ultra-low-field iMRI: interim analysis of a pros -
pective randomized trial.
Acta Neurochir Suppl
2011; 109: 49-53.
Diiscllosure
Authors report no conflict of interest.
References
1. Stupp R., Mason W.P., van den Bent M.J., et al. Radiotherapy
plus concomitant and adjuvant temozolomide for glioblastoma.
N Engl J Med
2005; 352: 987-996.
2. Lacroix M., Abi-Said D., Fourney D.R., et al. A multivariate
analysis of 416 patients with glioblastoma multiforme: prognosis,
extent of resection, and survival.
J Neurosurg
2001; 95: 190-198.
3. Laws E.R., Parney I.F., Huang W., et al. Survival following
surgery and prognostic factors for recently diagnosed malignant
glioma: data from the Glioma Outcomes Project.
J Neurosurg
2003; 99: 467-473.
4. Stummer W., Novotny A., Stepp H., et al. Fluorescence-guided
resection of glioblastoma multiforme by using 5-r resection of
malignant glioma: a randomised controlled multicentre phase
III trial; ALA-Glioma Study Group.
Lancet Oncol
2006; 7:
392-401.
5. Stummer W., Pichlmeier U., Meinel T., et al. Fluorescence-
guided surgery with 5-aminolevulinic acid foyrin accumulation
by C6 glioma cells after exposure to 5-aminolevulinic acid.
J Photochem Photobiol B
1998; 45: 160-169.
6. Nabavi A., Thurm H., Zountsas B., et al. Five-aminolevulinic
acid for fluorescence-guided resection of recurrent malignant
gliomas: a phase II study.
Neurosurgery
2009; 65: 1070-1076.
7. Stummer W., Novotny A., Stepp H., et al. Fluorescence-guided
resection of glioblastoma multiforme by using 5-aminolevulinic
acid-induced porphyrins: a prospective study in 52 consecutive
patients.
J Neurosurg
2000; 93: 1003-1013.
8. Jaffe E.K., Shanmugam D., Gardberg A., et al. Crystal structure
of Toxoplasma gondii porphobilinogen synthase: insights on
octameric structure and porphobilinogen formation.
J Biol Chem
2011; 286: 15298-15307.
9. Dhawan S., Weeks B.S., Soderland C., et al. HIV-1 infection
alters monocyte interactions with human microvascular
endothelial cells.
J Immunol
1995; 154: 422-432.
10. Stummer W., Tonn J.C., Mehdorn H.M., et al. Counterba -
lancing risks and gains from extended resections in malignant
51
Neurollogiia ii Neurochiirurgiia Pollska
2012; 46, 1
[ Pobierz całość w formacie PDF ]
