IV. RESULTADOS Y DISCUSIÓN
4.4 Comunicación familiar según el grado de discapacidad que presenta el niño(a) con
2.2. L a ser D o p p ler flo w m etry
Relative changes in m icrovascular perfusion were mea sured using the Oxford Array multi-channel Laser Doppler system (Oxford Optronix, Oxford U K ). The system in corporates up to 12 cylindrical probes each measuring 25 mm in length and 300 p,m in diameter with an estimated sampling volum e o f 1 0 mm^. A laser diode o f w ave length 780 nm is coupled to the probes which contain optical fibres (130 |xm in diameter) delivering and collect ing light to the tissue. M ovem ent o f red blood cells causes interaction with the photons o f light which are then Doppler shifted, this change in frequency is a measure o f blood velocity. The number o f Doppler shifts is propor tional to erythrocyte concentration (or blood volume). The product o f blood velocity and volum e is directly propor tional to red blood cell (R B C ) flux (or blood flow) and is generated as a signal [14].
An additional signal, the backscatter, is also recorded which is proportional to the total amount o f light detected by the probe. This is used to monitor movem ent o f a probe which w ill result in a change in the probe/tissue interface and an abrupt alteration in the backscatter signal. Apparent changes in red blood flux accompanied by a precipitous change in the backscatter reading were excluded from the analysis.
2.1. P atients 2.3. E xperim ental set-up
Eight patients were studied, six male, two fem ale, median age 63 years (range 4 6 to 86), all with h istological ly proven advanced m alignancy and all undergoing treat ment at Mount Vemon Centre for Cancer Treatment. Tumour characteristics are show n in Table 1. T w o patients (number 6 and 7) with multiple sites o f disease were studied on two separate occasions. Because o f the length o f the laser Doppler probes (25 mm) only superficial lesions could be studied. Written informed consent was obtained from all patients prior to measurements being taken, and approval for the study was given by Local Ethics Com m it tee.
Patients lay on a bed and up to six microprobes were inserted into the tumour. The probes are blunt ended and to facilitate entry into the lesion a 20-gauge cannula was inserted into the skin overlying the tumour. The probe was then advanced down the plastic sleeve, and lodged within the tumour (Fig. 1). Subcutaneous lignocaine (1%) was used to anaesthetise the skin prior to insertion o f the cannula. Since measurements were taken som e distance below the skin it was felt lignocaine would be unlikely to affect the readings. After a period o f equilibration baseline measurements were taken for 10 min. In all patients the probes were w ell tolerated for the observation period.
Table 1
Tumour characteristics and relative blood flow changes seen 6 m in after commencing carbogen breathing
Patient no. Tumour details Histology Relative blood flow 6 min into carbogen ( ± S.E.M.) 1* Abdominal skin deposit 4 cm Adenocarcinoma pancreas 1.13 (±0 .0 5 )
2 Breast 10 cm Adenocarcinoma 1.01 (±0 .1 1 )
3 Neck node 3.5 cm High grade non-Hodgkin lymphoma 0.85 (±0 .0 7 ) 4 ** Neck node 3 cm High grade non-Hodgkin lymphoma 2.24 (±0 .1 3 ) 5 Neck node 6 cm Squamous cell cancer supraglottis 1.07 (±0 .1 9 ) 6 Skin deposit abdomen 3 cm Adenocarcinoma colon 1.14 (±0 .1 8 )
Skin deposit abdomen 3.5 cm 1.06 (±0 .0 5 )
7 Groin node (R) 4 cm High grade non-Hodgkin lymphoma 0.81 (±0 .0 6 )
Groin node (L) 3 cm 0.96 (±0 .0 6 )
8 A xilla ry lymph node 3 cm Melanoma 1.25 (±0 .2 8 )
Analysis o f 10 min carbogen breathing period only because; *only 4 min post-carbogen observation period; * * a ll probes dislodged 3 m in into post-carbogen observation period.
M.E.B. Powell et al. / Radiotherapy and Oncology 41 ( 1996) 2 2 5 -231 227
Fig. I . Photograph showing six laser Doppler probes in situ within a skin nodule.
2.4. C arbogen breathing
F o llo w in g acq u isitio n o f baseline readings, a 10-m in period o f carbogen breathing was com m enced using a c lo s e -fittin g face mask (In te rsu rg ica l, U K .) covering both the nose and m outh. The carbogen (95% oxygen and 5% carbon d io x id e ) was delivered at a flo w rate o f 15 1 m in ” ' through a closed system using a 1-way valve and a 3-1 breathing bag.
M easurements were continued fo r a fu rth e r 10 m in after the cessation o f carbogen breathing w ith the patient breathing room air.
2.5. D ata a n a lysis
In d iv id u a l probes generate 20 readings per second. From this, an average flo w reading is calculated fo r each 2-m in in te rva l in a ll channels and plotted against tim e.
A p ro p o rtio n o f the signal is due to a b io lo g ic a l zero [1,6] w h ic h is p a rtly due to B ro w n ia n m o tio n o f the e rythrocytes in fro n t o f the probe. A n im a l data gives values fo r this background ‘ noise’ o f 30% and this c o rre ctio n fa cto r was applied to a ll o f the readings [2 ,11,16]. The fin a l plots o f red blo o d cell flu x together w ith the o rig in a l recorded data were exam ined and any traces show ing evidence o f patient m ovem ent o r probe m ovem ent were excluded fro m analysis.
F lo w d u rin g carbogen breathing was related to a baseline value w h ich was a single mean calculated fro m the measurements recorded over the 10-m in period p rio r to breathing carbogen, and was designated as the flo w at tim e zero. B lo o d flo w averages at 6, 10, 14 and 20 m in after starting carbogen breathing were com pared w ith the tim e
zero value using a paired tw o -ta ile d /-test where f < 0 .0 5 was considered to be significant.
3 . R e s u l t s
B lo o d flo w measurements were analysed in a total o f 50 leads in ten tum ours on eight patients. Patient num ber 6 w ith m u ltip le skin metastasis and patient num ber 7 w ith b ilateral inguinal lym phadenopathy were assessed on tw o separate occasions.
Carbogen breathing was tolerated w ith o u t d iffic u lty in all patients and thus the 10-m in carbogen breathing period co u ld be analysed in a ll 50 traces (seven were excluded due to m ovem ent artefact). H ow ever, tw o patients were not evaluable fo r the entire 10-m in post-carbogen observa tio n p eriod; patient num ber 1 had o n ly a 4 -m in post- carbogen observation period, and patient num ber 4 d is lodged a ll o f the probes on m ovem ent 3 m in after cessation o f carbogen. T h is a llo w e d analysis o f the w hole carbogen and post-carbogen breathing tim e in 39 traces fro m eight tum ours (fiv e traces were excluded due to m ovem ent).
F ig. 2 shows com plete data fro m these eight tum ours (34 traces). The values are expressed as a m e a n ± standard e rro r o f the mean. The data indicates that breathing carbogen does not influence R BC flu x. A s the patients sw itch to air breathing there is a m arginal increase in flu x w h ich then fa lls. S tatistical analysis o f relative blo o d flo w at 6 , 10 and 14 m in d id not show a sig n ifica n t va ria tio n fro m the pre-carbogen value ( f = 0.94, f = 0 . 9 0 , P = 0 .3 3 , re sp e ctive ly). The re la tive decrease in eryth ro cyte flu x a fter cessation o f carbogen breathing, how ever, d id g ive a
228 M.E.B. Powell et al. ! Radiotherapy and Oncology 41 (1996) 225-231 1.2-, 1.0- 0.« 0.6 0.4 0.2-1 0.0 "î- c a rb o g e n on c a rb o g e n o ff T im e in l\1inutes Fig. 2. tumours
Relative change in mean blood flow (± S .E .M .) from eight (34 leads) during and after 10 min o f carbogen breathing.
s ta tis tic a lly sig n ific a n t value at 20 m in (P = 0 .005) fro m tim e zero.
Data recorded fro m each o f the ten tum ours was analysed separately. The aim was firs t to acquire an ove ra ll v ie w o f the carbogen e ffe ct on blood fio w in a p a rticu la r tu m o u r and then, to study va ria tio n o f flu x in in d iv id u a l rnicroregions. F ig. 3, w h ich shows com plete data fro m fo u r patients, demonstrates the va ria tio n in response be tween patients to breathing carbogen.
Table 1 shows the re la tive blo o d flo w changes o f the ten tum ours at 6 m in. T h is tim e was selected since, as an average o f the readings between 4 and 6 m in a fter the start o f carbogen, it best reflects the use o f carbogen in c lin ic a l practice [ 8 ] and w o u ld indicate the effect o f carbogen on blood flo w at the start o f radiation. F our out o f ten tum ours
showed an increase in flo w after 6 m in o f carbogen breathing greater than 10% o f the pre-breathing value, w h ils t tw o tum ours showed a decrease and in tw o the flo w was unchanged.
V ariation o f e ryth ro cyte flu x and response to carbogen in d iffe re n t m icroregions o f a single tu m o u r are illu stra te d in Fig. 4, where the traces o f fo u r probes fro m patient 5 are shown (one trace was excluded due to excessive probe m ovem ent). There is m arked heterogeneity between the fo u r m icroregions not o n ly in terms o f m agnitude but also the d ire ctio n o f change in blo o d flo w . A sum m ary o f the e ffe ct o f carbogen on R B C flu x in a ll o f the in d iv id u a l traces is shown in Table 2. A t 6 m in , 60% o f traces demonstrated a change in blood flo w (37% increased, 23% decreased) and at 10 m in 6 8 % had altered (4 2 % increased, 26% decreased). The m agnitude o f change was modest, how ever, w ith o n ly 33% at 6 m in and 4 2% at 10 m in v a ry in g by 25% or more.
4 . D i s c u s s i o n
T u m o u r oxygenation depends upon blo o d flo w and oxygen d iffu s io n . The a d d ition o f 5% C O , to 95% oxygen aim ed to overcom e the vasoconstrictive e ffe ct o f oxygen. There is evidence fro m norm al tissue studies that carbon d io xid e acts on blood vessels causing enhanced blood flo w by vasodilatation, c a p illa ry re cru itm e n t and increased blood flo w v e lo c ity [5]. Im proved perfusion has been reported in m urine tum ours d u rin g carbogen breathing.
Patient 2 (5 traces) Patient 3 (6 traces)
O U_ o Cl Cl O Q o5 CO CO _J 0) > m OC 1.4 1.2- 1.0- 0.8- 0.6- 0.4- 0.2- 0.0
carbogen on carbogen off
5 10 15 Tim e in m inutes Patient 5 (4 traces) 1.4-1 1.2 1.0 0.8 0.6 0.4 0.2 0.0 ■ " f
carbogen on carbogen off
5 10 15 Tim e in m inutes 20 1.2 1.0- 0.8- 0.6 0.4 - 0.2- 0.0 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0
carbogen on carbogen off
5 10 15
Tim e in m inutes
20
Patient 6 (5 traces)
carbogen on carbogen off
5 10 15
Tim e in m inutes
M.E.B. Powell et al. / Radiotherapy and Oncology 41 (1996) 225-231 229 c Z3 2 '3 5 o 0) C L Q. O Q Q) C/D CÜ 4 0 0 -, 350 300 250 200 150 100 50 0
carbogen on carbogen off
0 -5 0 5 10 15 20