M. G. Dilkes

m-THPC photodynamic therapy for head and neck cancer

Over the past 30 months, the authors have treated a wide variety of head and neck cancer patients with meta-tetrahydroxyphenylchlorin (mTHPC)-mediated photodynamic therapy (PDT). This drug is a powerful, second-generation photosensitizer with significant advantages over earlier drugs. Treatment ranged from palliation and adjunctive to curative procedures. Results to date are very encouraging, with marked advantages over standard methods of treatment with respect to morbidity, both functional and aesthetic. Potential cure rates remain essentially unchanged, very much dependent on the stage of the tumour. These promising early results justify a multicentre study for treatment of early head and neck cancer using this drug and light combination. This is now underway.

Treatment of head and neck cancer with photodynamic therapy: results after one year

Photodynamic therapy (PDT) is a new and promising treatment modality for the treatment of malignant disease. This paper reports the preliminary experience of our group in the use of this therapy for the treatment of tumours arising in the head and neck. The majority of treatments in these cases have used a second generation systemic photosensitizer, meta-tetrahydroxyphenylchlorin (m-THPC). Two other cases were treated with either Photofrin 2 (a first generation systemic sensitizer) or with the topical photosensitizer, delta-aminolaevulinic acid (delta-ALA). The initial results have been encouraging with good clinical responses evident in patients presenting with a variety of differing tumour types. We feel there is now sufficient evident of the efficacy of this treatment to warrant a multicentre prospective study into the treatment of early head and neck cancer with PDT.

A comparison of novel light sources for photodynamic therapy.

A diode laser, light-emitting diode (LED) array bandwidth 25 nm, full width half maximum (FWHM) and filtered arc lamp (bandwidth 40 nm, FWHM), all with peak emission at about 650 nm, suitable for the photosensitizer tetra(meta-hydroxyphenyl)chlorin (mTHPC), were compared with a copper vapour laser pumped dye laser, using depth of necrosis in normal rat liver as a measure of photodynamic effect.A three-way comparison between a DL10K dye laser, the LED array and the filtered arc lamp resulted in mean depths of necrosis of 4.64, 4.29 and 4.04 mm, respectively, at 20 J cm-2, the values for the laser and arc lamp being significantly different at the 5% level. A further comparison of a narrower linewidth DL20K dye laser with the LED array, using a light dose of 20 J cm-2, showed a significant difference between the mean depths of necrosis of 4.97 and 4.05 mm, respectively (p=0.01).A final study, comparing the DL20K dye laser with the diode laser and a light dose of 10 J cm-2, demonstrated no significant difference in depths of necrosis (3.23 and 3.25 mm, respectively). The results obtained in the three studies are attributed to the relative bandwidths of light emission for the various sources. A simple mathematical model is presented explaining the results in terms of the relative activation of the photosensitizer and the consequent threshold fluence required for the induction of necrosis.It is concluded that, in order to achieve the same depth of effect as a laser when using the broad band sources, the incident fluence would have to be approximately doubled. However, when the low cost and ease of use of the non-laser sources are taken into consideration, these devices are likely to find widespread applications in clinical photodynamic therapy.

The use of the Hayek Oscillator during microlaryngeal surgery

An externally mounted cuirass ventilator, the Hayek Oscillator, was used on 41 patients undergoing surgery to the larynx without the use of a tracheal tube. Gas exchange and cardiovascular parameters remained satisfactory during the use of this technique, which offers a significant advance over existing tubeless methods of anaesthesia.

An in vivo comparison of the photodynamic action of a new diode laser and a copper vapour dye laser at 652 nm

Initial pre-clinical evaluation of a new 652 nm diode laser system for photodynamic therapy was performed to establish its efficacy in photo-activating the second-generation photosensitizer meta-tetrahydroxyphenychlorin (mTHPC). The diode laser was compared directly to a copper vapour laser pumped dye laser using depth of necrosis in normal rat liver as a measure of the photodynamic effect. No significant difference between the two lasers was observed.

A new method of tubeless anaesthesia for upper airway laser surgery

We have successfully used an externally mounted cuirass ventilator called the Hayek Oscillator to ventilate 15 patients undergoing laser surgery to the head and neck. Ventilation frequencies were in the range 60–180 cycles min−1, inspiratory pressures varied from −15 to −25 cm of water, expiratory pressures from +5 to +10 cm of water. This machine has overcome the major problem of safely oxygenating patients undergoing laser surgery to the upper aerodigestive tract while leaving the surgical field unencumbered. No complications were encountered.

PRELIMINARY EXPERIENCE WITH AN 810 NM WAVELENGTH DIODE LASER IN ENT SURGERY

The 810 nm diode laser delivers light with similar physical characteristics to the 1064 nm neodymium-yttrium aluminium garnet (Nd-YAG) laser. The diode laser was used in 25 ENT operations instead of the Nd-YAG laser. The laser has worked well and is a suitable surgical alternative to the Nd-YAG laser, with substantial advantages in terms of reliability and low cost ownership. The system size is 391×387 × 160 mm, and it weighs only 11 kg. The high efficiency of the laser diodes allows the system to be run from a standard wall socket electrical supply of less than 1 amp.

Meta-tetrahydroxyphenylchlorin (mTHPC) mediated photodynamic therapy: experience and thoughts after 17 treatments

Over the past 14 months we have treated a wide variety of head and neck cancer patients with mTHPC mediated photodynamic therapy. This drug is a very powerful second generation photosensitizer with significant advantages over earlier drugs. Patients treated range from palliative to primary (curative) to adjunctive (intraoperative) cases. Following promising results we are now setting up a multicenter European study to treat early head and neck cancer with this drug/light combination, along with other collaborative studies to look further at the role of adjunctive PDT.

New LED source for photodynamic therapy: preclinical study

Preclinical studies of a new light emitting diode light source suitable for photodynamic therapy at 650 nm are described. The light source is found to produce effective cell kill using the colo26 cell line and the photosensitizer m-THPC. The performance of the LED source for PDT in tissue is evaluated in comparison with a copper vapor pumped dye laser by measuring depth of necrosis obtained in normal rat liver. Similar depths of necrosis are obtained. It is concluded that the device shows promise as an alternative light source for photodynamic therapy with m-THPC.

Tissue photosensitizer detection by low-power remittance fluorimetry

A simple adaptation of a commercial spectrofluorimeter which allows the semiquantitative determination of photodynamic therapy photosensitizer fluorescence in accessible tissues is described. Light from a xenon lamp is directed via a monochromator onto the tissue surface by a bifurcated random fibre bundle. Tissue fluorescence is directed to the emission monochromator and photomultiplier of the fluorimeter by the second limb of the fibre bundle. Although relatively simple, this device can be used to carry out a wide range of useful measurements in clinical and experimental photodynamic therapy. The sensitivity and reproducibility of the measurements were determined using mouse tumour and muscle tissue fluorescence measured in vivo compared with photosensitizer content measured by high performance liquid chromatography. As an illustration of the potential applications of such systems, the time courses of fluorescence in the skin of patients treated with the photosensitizers Photofrin® and metatetra(hydroxyphenyl)chlorin (mTHPC) (temoporfin) and the photobleaching of 5-aminolaevulinic acid-derived protoporphyrin IX during treatment, are described.