Biomedical Engineering Reference
In-Depth Information
Pain Experienced During PDT
During illumination, a sensation of stinging or burning sensa-
tions is frequently observed, which can range from mild to
severe and varies from patient to patient. The precise mecha-
nism of pain is not fully elucidated but likely involves nerve
stimulation and/or tissue damage (188).
A review study by Warren and colleagues (188) of 43 articles
consisting of clinical PDT trials (2000-2008) that used ALA or
MAL was performed to summarize the effectiveness of inter-
ventions to reduce ALA-PDT-related pain and to explore con-
tributing factors to pain induction. Their consensus opinion is
that, in general, topical anesthetics do not work and cooling
the skin with either ice water or with a high-airfl ow cooling
device (such as Zimmer MedizinSystems, Irvine, California,
USA) represents the best topical intervention to control the
pain during PDT. They also found that pain intensity is associ-
ated with lesion size and location; certain diagnoses, particu-
larly plaque-type psoriasis, appear to generate the highest
PDT-related pain scores. Inconsistent results were encoun-
tered for the correlation of pain with light source, wavelength
of light, fl uence rate, and total light dose.
Although the use of forced airfl ow cooling device (ACD)
appears to be effective in reducing pain during PDT, a recent
nonrandomized retrospective observational controlled study
conducted by Tyrrell and colleagues (189) demonstrated that
patients using ACD throughout treatment presented signifi -
cantly less PpIX photobleaching than the control group. The
100 lesions (in 100 patients) investigated in this study included:
39 AK, 29 sBCCs, and 32 BD. After comparing the data from
50 patients who utilized the ACD throughout irradiation with
the other 50 patients not requiring any pain relief, the authors
found 82% complete response in the non-ACD group versus
only 68% complete response in the ACD group (including all
three lesion types). As demonstrated by previous studies
(190,191), the level of PpIX photobleaching correlates to cell
death and therefore tumor clearance rates and might be the
reason that utilization of the ACD during light irradiation
lowers the potential effi cacy of the treatment. Furthermore,
AK lesions using the ACD were more susceptible to reduced
PpIX photobleaching when compared with PpIX accumula-
tion indicating a potential reduction in treatment effi cacy. It is
proposed that the low temperature of air used may cause local
vasoconstriction, reducing reactive oxygen species (ROS) pro-
duction and thus limiting clinical effectiveness.
The effi cacy of subcutaneous infi ltration anesthesia (SIA) on
pain in PDT was demonstrated in a study conducted by Borelli
and colleagues (192). They compared the pain related to ALA-
PDT in 16 patients who received oral analgesics (1 g paracetamol,
20 mg codeine) and SIA on one side of the face, containing a
mixture of ropivacaine, prilocaine, and epinephrine. Signifi -
cantly less pain was reported by 94% of the patients with SIA.
However, subcutaneous infi ltration anesthesia should not con-
tain vasoconstrictors, such as epinephrine, as their use could
reduce the oxygen supply in the skin and thus compromise the
effectiveness of PDT.
It should be noted that the infl uence of irradiation on
the pain experienced during topical PDT is still a matter of
debate. Preliminary studies of prototype devices consisting of
portable LED sources (2 cm diameter, 45-60 J/cm 2 , red light,
550-750 nm, irradiance 5 mW/cm 2 ) showed that low-
irradiance PDT could be effectively used and was signifi cantly
less painful (193). Twelve patients (eight with BD and four
with sBCC <2 cm in diameter) received two treatments,
1 month apart following ALA 20% cream incubation of
4 hours. At 12-month follow-up, seven of the 12 patients had a
complete response while the pain scores using a numerical rat-
ing scale were referred as <2 by all 12 patients.
Another study conducted by Wiegell and colleagues (194)
evaluated continuous activation of PpIX by daylight and found
to be as effective as and less painful than conventional PDT for
AK. Twenty-nine patients with AK of the face and scalp had
two symmetrical areas treated with MAL-PDT: one was illumi-
nated by red LED light using standard parameters (632 nm,
37 J/cm 2 ) after 3 hours of incubation and the other was treated
with daylight for 2.5 hours after half hour incubation. At the
3-month follow-up, no signifi cant difference in the treatment
effect between the two was observed, with a reduction in AK of
71% in the LED-treated area versus 79% in the daylight-treated
area. Treatment with daylight was signifi cantly less painful than
with LED light with a mean maximal score (numerical scale
from 0 to 10) during daylight exposure of 2 compared with 6.7
during LED exposure. Therefore the authors concluded that
daylight PDT could be an effective, nearly pain-free alternative
to conventional PDT for patients with thin AK. However, it is
unlikely that ambient light exposure can offer a practical, safe,
and consistent method to the delivery of PDT.
practical considerations
Patient Selection for ALA-PDT
Thoughtful selection of eligible patients for ALA-PDT benefi ts
both physician and patient. Patients should be carefully screened
at an initial clinical consultation for inclusion and exclusion
criteria for PDT. Physicians should gauge whether a patient has
an accurate understanding and realistic expectations of the pro-
cedure. This will maximize patient results, reduce patient anxi-
ety, and ensure the PDT is conducted smoothly on the day of
the procedure. A comprehensive consent that explains the risks,
benefi ts, and complications of therapy as well as treatment
alternatives should be reviewed with patients carefully prior to
treatment.
Exclusion Criteria
Patients should be screened for important exclusion criteria
prior to undergoing PDT. A history of photosensitivity, includ-
ing porphyria, photodermatoses, and photosensitizing medi-
cation use should preclude treatment (72,82,168). Many
studies have excluded patients from treatment if they have
undergone treatment with systemic retinoids, chemotherapeu-
tic agents, or immunotherapy in the past 6 months (68,82,175).
Pregnant or nursing women and individuals with an active
infection should not undergo treatment (67,68). Patients
should refrain from topical retinoids, alpha hydroxy acids, and
chemical peels approximately 1 month prior to treatment (82).
Treatment Protocol
Skin Preparation
Optimal results following ALA-PDT can be achieved with
proper preparation prior to the procedure itself. The stratum
 
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